Georg F Hoffmann

Summary

Affiliation: University of Heidelberg
Country: Germany

Publications

  1. ncbi request reprint Tyrosine hydroxylase deficiency causes progressive encephalopathy and dopa-nonresponsive dystonia
    Georg F Hoffmann
    Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
    Ann Neurol 54:S56-65. 2003
  2. ncbi request reprint Acrodermatitis acidaemia secondary to 'overtreatment' and protein deficiency
    G F Hoffmann
    University Childrens Hospital Heidelberg, Heidelberg, Germany
    J Inherit Metab Dis 29:173-4. 2006
  3. doi request reprint Low lysine diet in glutaric aciduria type I--effect on anthropometric and biochemical follow-up parameters
    Nikolas Boy
    Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Hospital Heidelberg, Heidelberg, Germany
    J Inherit Metab Dis 36:525-33. 2013
  4. ncbi request reprint Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision
    Nikolas Boy
    Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D 69120, Heidelberg, Germany
    J Inherit Metab Dis . 2016
  5. ncbi request reprint Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency
    Sven W Sauer
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital Heidelberg, Heidelberg, Germany
    J Neurochem 97:899-910. 2006
  6. pmc Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Evaluation of Genotype-Phenotype Correlation in Patients Detected by Newborn Screening
    Gwendolyn Gramer
    Department of General Paediatrics, Division for Neuropaediatrics and Metabolic Medicine, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
    JIMD Rep 23:101-12. 2015
  7. pmc A cross-sectional controlled developmental study of neuropsychological functions in patients with glutaric aciduria type I
    Nikolas Boy
    Department of General Paediatrics, Division of Child Neurology and Inherited Metabolic Diseases, Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D 69120, Heidelberg, Germany
    Orphanet J Rare Dis 10:163. 2015
  8. doi request reprint Pitfalls in phenylalanine loading test in the diagnosis of dopa-responsive dystonia
    Thomas Opladen
    Division of Inborn Metabolic Diseases, University Children s Hospital, Heidelberg, Germany
    Mol Genet Metab 108:195-7. 2013
  9. ncbi request reprint Incidence and short-term outcome of children with symptomatic presentation of organic acid and fatty acid oxidation disorders in Germany
    Daniela A Klose
    Division of Metabolic and Endocrine Disorders, University Children s Hospital, Heidelberg, Germany
    Pediatrics 110:1204-11. 2002
  10. doi request reprint Newborn screening for remethylation disorders and vitamin B12 deficiency-evaluation of new strategies in cohorts from Qatar and Germany
    Gwendolyn Gramer
    Center for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany
    World J Pediatr . 2017

Detail Information

Publications115 found, 100 shown here

  1. ncbi request reprint Tyrosine hydroxylase deficiency causes progressive encephalopathy and dopa-nonresponsive dystonia
    Georg F Hoffmann
    Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
    Ann Neurol 54:S56-65. 2003
    ..Investigations of neurotransmitter defects by specific cerebrospinal fluid determinations should be included in the diagnostic evaluation of children with progressive infantile encephalopathy...
  2. ncbi request reprint Acrodermatitis acidaemia secondary to 'overtreatment' and protein deficiency
    G F Hoffmann
    University Childrens Hospital Heidelberg, Heidelberg, Germany
    J Inherit Metab Dis 29:173-4. 2006
  3. doi request reprint Low lysine diet in glutaric aciduria type I--effect on anthropometric and biochemical follow-up parameters
    Nikolas Boy
    Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Hospital Heidelberg, Heidelberg, Germany
    J Inherit Metab Dis 36:525-33. 2013
    ..However, possible affection of linear growth, weight gain and biochemical follow-up monitoring has not been studied systematically...
  4. ncbi request reprint Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision
    Nikolas Boy
    Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D 69120, Heidelberg, Germany
    J Inherit Metab Dis . 2016
    ..J Inherit Metab Dis 30:5-22, 2007b; J Inherit Metab Dis 34:677-694, 2011) and add new research findings, relevant clinical aspects, and the perspective of affected individuals...
  5. ncbi request reprint Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency
    Sven W Sauer
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital Heidelberg, Heidelberg, Germany
    J Neurochem 97:899-910. 2006
    ..In conclusion, we propose that an intracerebral de novo synthesis and subsequent trapping of GA and 3-OH-GA should be considered as a biochemical risk factor for neurodegeneration in GCDH deficiency...
  6. pmc Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Evaluation of Genotype-Phenotype Correlation in Patients Detected by Newborn Screening
    Gwendolyn Gramer
    Department of General Paediatrics, Division for Neuropaediatrics and Metabolic Medicine, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
    JIMD Rep 23:101-12. 2015
    ..985A>G in the ACADM gene, potentially mild mutations like c.199T>C are frequently found in screening cohorts. There is ongoing discussion whether this mutation is associated with a clinical phenotype...
  7. pmc A cross-sectional controlled developmental study of neuropsychological functions in patients with glutaric aciduria type I
    Nikolas Boy
    Department of General Paediatrics, Division of Child Neurology and Inherited Metabolic Diseases, Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D 69120, Heidelberg, Germany
    Orphanet J Rare Dis 10:163. 2015
    ..Glutaric aciduria type I (GA-I) is an inherited metabolic disease due to deficiency of glutaryl-CoA dehydrogenase (GCDH). Cognitive functions are generally thought to be spared, but have not yet been studied in detail...
  8. doi request reprint Pitfalls in phenylalanine loading test in the diagnosis of dopa-responsive dystonia
    Thomas Opladen
    Division of Inborn Metabolic Diseases, University Children s Hospital, Heidelberg, Germany
    Mol Genet Metab 108:195-7. 2013
    ..These data suggest activation of hepatic phenylalanine hydroxylase by BH(4). Thus, the Phe loading test should not be performed during substitution with BH(4)...
  9. ncbi request reprint Incidence and short-term outcome of children with symptomatic presentation of organic acid and fatty acid oxidation disorders in Germany
    Daniela A Klose
    Division of Metabolic and Endocrine Disorders, University Children s Hospital, Heidelberg, Germany
    Pediatrics 110:1204-11. 2002
    ..To determine the incidence of symptomatic children with inherited organic acid disorders (OADs) and fatty acid oxidation disorders (FAODs) in Germany...
  10. doi request reprint Newborn screening for remethylation disorders and vitamin B12 deficiency-evaluation of new strategies in cohorts from Qatar and Germany
    Gwendolyn Gramer
    Center for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany
    World J Pediatr . 2017
    ..Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar...
  11. ncbi request reprint Newborn Screening for Vitamin B6 Non-responsive Classical Homocystinuria: Systematical Evaluation of a Two-Tier Strategy
    Jürgen G Okun
    Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children s Hospital, Heidelberg, Germany
    JIMD Rep . 2016
    ..2.1.22) there is a clear evidence for the success of early treatment. The aim of this study was to develop and evaluate a two-tier strategy for HCU newborn screening...
  12. doi request reprint Newborn screening for severe combined immunodeficiency using a novel and simplified method to measure T-cell excision circles (TREC)
    Laura Tagliaferri
    Department of Pediatric Oncology, Hematology and Immunology, Children s Hospital, University of Heidelberg, Heidelberg, Germany Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Fondazione IRCCS Ca randa, Ospedale Maggiore Policlinico, Milan, Italy
    Clin Immunol . 2016
    ..In comparison to established methods, our test requires only 25% of the input material, doesn't require DNA purification and significantly reduces time and cost requirement...
  13. ncbi request reprint Newborn Screening Programmes in Europe, Arguments and Efforts Regarding Harmonisation: Focus on Organic Acidurias
    Friederike Hörster
    Division of Neuropediatrics and Inherited Metabolic Diseases, Department of General Pediatrics, University Children s Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
    JIMD Rep . 2016
    ....
  14. doi request reprint Genetic cause and prevalence of hydroxyprolinemia
    Christian Staufner
    Department of General Pediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, 69120, Heidelberg, Germany
    J Inherit Metab Dis 39:625-32. 2016
    ..In MS/MS newborn screening, the mass spectrum of hydroxyproline cannot be differentiated from isoleucine and leucine causing false positive newborn screening test results for maple syrup urine disease (MSUD)...
  15. doi request reprint Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders--review and meta-analysis of observational studies published over more than 35 years
    Peter Burgard
    Centre for Paediatric and Adolescent Medicine, Division for Neuropaediatrics and Metabolic Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, D 69120, Heidelberg, Germany
    J Inherit Metab Dis 39:219-29. 2016
    ..We aimed to integrate available evidence to create benchmarks for new diagnostic and therapeutic strategies...
  16. doi request reprint Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options
    Christian Staufner
    Department of General Pediatrics, Division of Pediatric Metabolic Medicine and Neuropediatrics, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
    J Inherit Metab Dis 39:273-83. 2016
    ..Adenosine kinase deficiency is a recently described defect affecting methionine metabolism with a severe clinical phenotype comprising mainly neurological and hepatic impairment and dysmorphism...
  17. doi request reprint Living with an inborn error of metabolism detected by newborn screening-parents' perspectives on child development and impact on family life
    Gwendolyn Gramer
    Department of General Paediatrics, Division of Metabolic Disorders, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
    J Inherit Metab Dis 37:189-95. 2014
    ..Newborn screening for inborn errors of metabolism is regarded as highly successful by health professionals. Little is known about parents' perspectives on child development and social impact on families...
  18. doi request reprint Complementary dietary treatment using lysine-free, arginine-fortified amino acid supplements in glutaric aciduria type I - A decade of experience
    Stefan Kölker
    Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Hospital Heidelberg, Heidelberg, Germany
    Mol Genet Metab 107:72-80. 2012
    ....
  19. doi request reprint Use of guidelines improves the neurological outcome in glutaric aciduria type I
    Jana Heringer
    Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Hospital Heidelberg, Heidelberg, Germany
    Ann Neurol 68:743-52. 2010
    ..To evaluate the effect of treatment according to current evidence-based recommendations on the neurological outcome of patients with glutaric aciduria type I (GA-I)...
  20. doi request reprint Impact of short- and medium-chain organic acids, acylcarnitines, and acyl-CoAs on mitochondrial energy metabolism
    Sven Wolfgang Sauer
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital, Heidelberg, Germany
    Biochim Biophys Acta 1777:1276-82. 2008
    ....
  21. ncbi request reprint Decline of acute encephalopathic crises in children with glutaryl-CoA dehydrogenase deficiency identified by newborn screening in Germany
    Stefan Kölker
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital Heidelberg, D 69120 Heidelberg, Germany
    Pediatr Res 62:357-63. 2007
    ..No patient was known to be missed by newborn screening from 1999 to 2005. In conclusion, this study confirms that newborn screening for GCDH deficiency in combination with intensive management is beneficial...
  22. ncbi request reprint Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA, cblB)
    Friederike Hörster
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital, D 69120 Heidelberg, Germany
    Pediatr Res 62:225-30. 2007
    ..In addition, long-term outcome was dependent on the age cohort and cobalamin responsiveness...
  23. ncbi request reprint Atypical case of Aicardi-Goutières syndrome with late-onset myoclonic status
    Andrea Berger
    Centre of Epileptology, Paediatric Neurology, Kehl Kork, Germany
    Epileptic Disord 9:140-4. 2007
    ..Clinical deterioration occurred later, and at the age of 17 years he experienced severe, generalized, myoclonic attacks lasting hours, which were partly controlled by the administration of piracetam.[Published with video sequences]...
  24. ncbi request reprint Feature construction can improve diagnostic criteria for high-dimensional metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency
    Sirikit Ho
    Division of Metabolic Diseases, Department of General Pediatrics, University Children s Hospital, Heidelberg, Germany
    Clin Chem 53:1330-7. 2007
    ..Published diagnostic criteria for these disorders normally incorporate a primary metabolic marker combined with secondary markers, often analyte ratios, for which the markers have been chosen to reflect metabolic pathway deviations...
  25. pmc Mevalonate kinase deficiencies: from mevalonic aciduria to hyperimmunoglobulinemia D syndrome
    Dorothea Haas
    Department of General Pediatrics, University Children s Hospital Heidelberg, Im Neuenheimer Feld 150, D 69120 Heidelberg, Germany
    Orphanet J Rare Dis 1:13. 2006
    ..Genetic counseling should be offered to families at risk. There is no established successful treatment for MVA. Simvastatin, an inhibitor of HMG-CoA reductase, and anakinra have been shown to have beneficial effect in HIDS...
  26. ncbi request reprint Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency
    Stefan Kölker
    Department of General Pediatric, University of Children s Hospital Heidelberg, D 69120 Heidelberg, Germany
    Pediatr Res 59:840-7. 2006
    ..Notably, the biochemical phenotype did not predict the clinical phenotype. Our study proves GCDH deficiency to be a treatable disorder and a good candidate for neonatal screening...
  27. ncbi request reprint Comprehensive detection of disorders of purine and pyrimidine metabolism by HPLC with electrospray ionization tandem mass spectrometry
    Susen Hartmann
    Division of Metabolic Diseases, Department of General Pediatrics, University Children s Hospital Heidelberg, Heidelberg, Germany
    Clin Chem 52:1127-37. 2006
    ..We present a method that allows comprehensive, sensitive, and specific diagnosis of the entire spectrum of abnormalities in purine and pyrimidine metabolism in 1 analytical run...
  28. ncbi request reprint Phenylalanine reduces synaptic density in mixed cortical cultures from mice
    Friederike Hörster
    Department of General Pediatrics, University of Children s Hospital, Heidelberg, Germany
    Pediatr Res 59:544-8. 2006
    ....
  29. ncbi request reprint Plasma and thrombocyte levels of coenzyme Q10 in children with Smith-Lemli-Opitz syndrome (SLOS) and the influence of HMG-CoA reductase inhibitors
    Dorothea Haas
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Hospital Heidelberg, Heidelberg, Germany
    Biofactors 32:191-7. 2008
    ..The aim of this study was to analyse plasma and intracellular CoQ10 levels in SLOS patients and to determine the influence of HMG-CoA reductase inhibitors...
  30. doi request reprint One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects
    Jochen Meyburg
    Department of General Pediatrics, University Children s Hospital, Heidelberg, Germany
    Transplantation 87:636-41. 2009
    ..They are promising target diseases for liver cell transplantation (LCT), which may be a less invasive alternative or supplementation to orthotopic liver transplantation...
  31. doi request reprint Initial evaluation of a biochemical cystic fibrosis newborn screening by sequential analysis of immunoreactive trypsinogen and pancreatitis-associated protein (IRT/PAP) as a strategy that does not involve DNA testing in a Northern European population
    Olaf Sommerburg
    Division of Paediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Paediatrics III, University of Heidelberg, Im Neuenheimer Feld 430, Heidelberg, Germany
    J Inherit Metab Dis 33:S263-71. 2010
    ....
  32. doi request reprint Phenylalanine loading in pediatric patients with dopa-responsive dystonia: revised test protocol and pediatric cutoff values
    Thomas Opladen
    Division of Inherited Metabolic Diseases, University Children s Hospital Heidelberg, Heidelberg, Germany
    J Inherit Metab Dis 33:697-703. 2010
    ..The objectives of this study were to determine the value of phenylalanine (Phe) loading for diagnosing dopa-responsive dystonia (DRD) in children...
  33. doi request reprint Newborn screening for disorders of fatty-acid oxidation: experience and recommendations from an expert meeting
    Martin Lindner
    University Children s Hospital, Heidelberg, Germany
    J Inherit Metab Dis 33:521-6. 2010
    ..As a final conclusion, the accumulated evidence suggests all FAOD should to be included into tandem mass spectrometry (MS/MS)-based NBS programs provided sufficient laboratory performance is guaranteed...
  34. doi request reprint Liver, liver cell and stem cell transplantation for the treatment of urea cycle defects
    Jochen Meyburg
    Department of General Pediatrics, University Children s Hospital, Heidelberg, Germany
    Mol Genet Metab 100:S77-83. 2010
    ..However, a clear proof of principle in animal models of human metabolic disease is still missing, which is the prerequisite for clinical application in humans...
  35. doi request reprint Monitoring of intraportal liver cell application in children
    Jochen Meyburg
    Department of General Pediatrics, University Children s Hospital, Heidelberg, Germany
    Cell Transplant 19:629-38. 2010
    ..Time courses for changes in PVF, PVP, and liver enzymes were obtained. Thorough monitoring of portal vein pressure and duplex sonography according to a defined protocol is likely to increase safety of cell application in pediatric LCT...
  36. pmc Principles of pediatric emergency care
    Jochen Meyburg
    Abteilung Allgemeine Pädiatrie, Zentrum für Kinder und Jugendmedizin, Universitatsklinikum Heidelberg, Germany
    Dtsch Arztebl Int 106:739-47; quiz 748. 2009
    ..Children account for only a small percentage of pre-hospital emergency patients but are a special challenge for the treating physician...
  37. doi request reprint Liver cell transplantation in children
    Jochen Meyburg
    Department of General Paediatrics, University Children s Hospital, Heidelberg, Germany
    Clin Transplant 23:75-82. 2009
    ..Nevertheless, these individual therapeutic attempts of LCT yielded encouraging results, and prospective studies should be initiated...
  38. doi request reprint Relevance of allosteric conformations and homocarnosine concentration on carnosinase activity
    Verena Peters
    Division of Metabolic Diseases, University Children s Hospital, Heidelberg, Germany
    Amino Acids 38:1607-15. 2010
    ..Homocarnosine treatment can be expected to reduce CN1 activity toward carnosine, resulting in higher carnosine levels...
  39. doi request reprint Liver cell transplantation: basic investigations for safe application in infants and small children
    Jochen Meyburg
    Department of General Pediatrics, University Children s Hospital, 69120 Heidelberg, Germany
    Cell Transplant 18:777-86. 2009
    ..We conclude that especially with the use of small catheters, human LCT should be safe and efficient even in small infants and neonates...
  40. doi request reprint A new pediatric liver transplantation program in Southern Germany. The Heidelberg experience
    Guido Engelmann
    Department of Pediatrics, University Hospital, Heidelberg, Germany
    Pediatr Transplant 14:12-8. 2010
    ..In the pilot phase, small children and infants have to be referred and transplanted in an established center. An interdisciplinary team of specialists closely working together is the key for sustained success...
  41. doi request reprint Therapeutic modulation of cerebral L-lysine metabolism in a mouse model for glutaric aciduria type I
    Sven W Sauer
    Department of General Paediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital, Im Neuenheimer Feld 430, D 69120 Heidelberg, Germany
    Brain 134:157-70. 2011
    ....
  42. ncbi request reprint Evaluation of 6-year application of the enzymatic colorimetric phenylalanine assay in the setting of neonatal screening for phenylketonuria
    Andreas Schulze
    Division of Metabolic and Endocrine Diseases, University Children s Hospital, Im Neuenheimer Feld 150, 69120, Heidelberg, Germany
    Clin Chim Acta 317:27-37. 2002
    ..The aim of this study was to evaluate an enzymatic phenylalanine (Phe) determination in the whole context spanning from the initial investigation over the recall period, up to the confirmation or exclusion of the disease...
  43. ncbi request reprint Pathomechanisms of neurodegeneration in glutaryl-CoA dehydrogenase deficiency
    Stefan Kölker
    Division of Metabolic and Endocrine Diseases, University Children s Hospital, Heidelberg, Germany
    Ann Neurol 55:7-12. 2004
    ..Finally, maturation-dependent changes in the expression of neuronal glutamate receptors may affect the vulnerability to 3-hydroxyglutaric and glutaric acid toxicity...
  44. ncbi request reprint Methylmalonic acid, a biochemical hallmark of methylmalonic acidurias but no inhibitor of mitochondrial respiratory chain
    Stefan Kölker
    Department of General Pediatrics, Division of Metabolic and Endocrine Diseases, University Children s Hospital Heidelberg, D 69120 Heidelberg, Germany
    J Biol Chem 278:47388-93. 2003
    ..Inhibition of respiratory chain and tricarboxylic acid cycle is most likely induced by synergistically acting alternative metabolites, in particular 2-methylcitric acid, malonic acid, and propionyl-CoA...
  45. ncbi request reprint Optimized spectrophotometric assay for the completely activated pyruvate dehydrogenase complex in fibroblasts
    Marina A Schwab
    Division of Metabolic and Endocrine Diseases, University Children s Hospital Heidelberg, 69120 Heidelberg, Germany
    Clin Chem 51:151-60. 2005
    ..The most commonly used radiochemical method detects the formation of (14)CO(2), an endproduct of the E1 component of PDHc, from [1-(14)C]pyruvate...
  46. ncbi request reprint Accurate measurement of free carnitine in dried blood spots by isotope-dilution electrospray tandem mass spectrometry without butylation
    Andreas Schulze
    Division of Metabolic and Endocrine Diseases, Department of General Pediatrics, University Children s Hospital, Im Neuenheimer Feld 153, D 69120 Heidelberg, Germany
    Clin Chim Acta 335:137-45. 2003
    ..To test the feasibility of free carnitine (FC) determination in dried blood spot specimens (DBS) by stable isotope-dilution electrospray-ionisation tandem mass spectrometry (MS/MS)...
  47. ncbi request reprint Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications
    Andreas Schulze
    Division of Metabolic and Endocrine Diseases, Department of General Pediatrics, University Children s Hospital, Heidelberg, Germany
    Pediatrics 111:1399-406. 2003
    ....
  48. ncbi request reprint Chronic treatment with glutaric acid induces partial tolerance to excitotoxicity in neuronal cultures from chick embryo telencephalons
    Stefan Kölker
    Division of Metabolic and Endocrine Diseases, University Children s Hospital, Heidelberg, Germany
    J Neurosci Res 68:424-31. 2002
    ....
  49. ncbi request reprint Lack of creatine in muscle and brain in an adult with GAMT deficiency
    Andreas Schulze
    Division of Metabolic and Endocrine Diseases, Department of General Pediatrics, University Children s Hospital, Heidelberg, Germany
    Ann Neurol 53:248-51. 2003
    ....
  50. ncbi request reprint Acylcarnitine profiles of preterm infants over the first four weeks of life
    Jochen Meyburg
    Department of Neonatology, Division of Metabolic and Endocrine Diseases, University Children s Hospital, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany
    Pediatr Res 52:720-3. 2002
    ..However, the commonly used metabolite ratios should still allow the detection of inborn errors of metabolism...
  51. ncbi request reprint A method for quantitative acylcarnitine profiling in human skin fibroblasts using unlabelled palmitic acid: diagnosis of fatty acid oxidation disorders and differentiation between biochemical phenotypes of MCAD deficiency
    Jürgen G Okun
    Division of Metabolic and Endocrine Diseases, Department of General Pediatrics, University Children s Hospital, Im Neuenheimer Feld 150, D 69120 Heidelberg, Germany
    Biochim Biophys Acta 1584:91-8. 2002
    ..In conclusion, this novel technique is a powerful tool for the investigation of fatty acid oxidation disorders under standardized conditions in fibroblasts...
  52. ncbi request reprint Ca(2+) and Na(+) dependence of 3-hydroxyglutarate-induced excitotoxicity in primary neuronal cultures from chick embryo telencephalons
    Stefan Kölker
    Division of Metabolic and Endocrine Diseases, University Children s Hospital, Heidelberg, Germany
    Pediatr Res 52:199-206. 2002
    ..In conclusion, the present study revealed that NMDA receptor activation and subsequent disturbance of Ca(2+) homeostasis contribute to 3-OH-GA-induced cell damage...
  53. ncbi request reprint Neurodegeneration in methylmalonic aciduria involves inhibition of complex II and the tricarboxylic acid cycle, and synergistically acting excitotoxicity
    Jürgen G Okun
    Department of Pediatrics, Division of Metabolic and Endocrine Diseases, Im Neuenheimer Feld 150, Federal Republic of Germany
    J Biol Chem 277:14674-80. 2002
    ..We propose that neuropathogenesis of methylmalonic aciduria may involve an inhibition of complex II and the tricarboxylic acid cycle by accumulating toxic organic acids, and synergistic secondary excitotoxic mechanisms...
  54. ncbi request reprint Liver transplantation for inborn errors of metabolism
    Jochen Meyburg
    Department of General Pediatrics, Division of Metabolic and Endocrine Diseases, University Children s Hospital, Heidelberg, Germany
    Transplantation 80:S135-7. 2005
    ..In most hepatic-based metabolic disorders, restoration of only about 10% of the original enzyme activity is sufficient to warrant sufficient metabolic control...
  55. doi request reprint Significant prevalence of sickle cell disease in Southwest Germany: results from a birth cohort study indicate the necessity for newborn screening
    Joachim B Kunz
    Department of Pediatric Oncology, Hematology, Oncology and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, D 69120, Heidelberg, Germany
    Ann Hematol 95:397-402. 2016
    ..Together with previously published even higher results from exclusively urban populations in Berlin and Hamburg, our data provide the basis for the decision on a newborn screening program for SCD in Germany. ..
  56. doi request reprint Co-expression of phenylalanine hydroxylase variants and effects of interallelic complementation on in vitro enzyme activity and genotype-phenotype correlation
    Nan Shen
    Dietmar Hopp Metabolic Center, University Children s Hospital, Department of General Pediatrics, Heidelberg, Germany
    Mol Genet Metab 117:328-35. 2016
    ....
  57. ncbi request reprint Mutations in the AUH gene cause 3-methylglutaconic aciduria type I
    T B Nga Ly
    Department of General Paediatrics, Ruprecht Karls University, Heidelberg, Germany
    Hum Mutat 21:401-7. 2003
    ..Further work is required to identify external or genetic factors associated with development of clinical problems in patients with MGA1...
  58. ncbi request reprint Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany
    Georg F Hoffmann
    Department of Paediatrics, University of Heidelberg, Germany
    Eur J Pediatr 163:76-80. 2004
    ..These conditions were related to considerable morbidity and mortality. Considerations for their inclusion in expanded newborn screening programmes might be warranted...
  59. ncbi request reprint Analysis of the functional muscle-bone unit of the forearm in patients with phenylketonuria by peripheral quantitative computed tomography
    Daniela Choukair
    Department of Pediatrics I, University Children s Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
    J Inherit Metab Dis . 2016
    ..These alterations indicate a mixed bone defect in PKU, both of which are due to primary alterations of bone metabolism and to secondary alterations in response to neuromuscular abnormalities...
  60. doi request reprint Defining the hidden evidence in autism research. Forty per cent of rigorously designed clinical trials remain unpublished - a cross-sectional analysis
    Konstantin Mechler
    Paediatric Psychopharmacology, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
    Int J Methods Psychiatr Res . 2016
    ..The results emphasize the serious issue of publication bias. The large proportion of unpublished results precludes valuable information and has the potential to distort evidence for treatment approaches in ASD...
  61. pmc CRISPR RNA-guided FokI nucleases repair a PAH variant in a phenylketonuria model
    Yi Pan
    Division of Functional Genome Analysis, German Cancer Research Center DKFZ, Heidelberg, Germany
    Sci Rep 6:35794. 2016
    ..This proof-of-concept indicates the potential of the FokI-dCas9 system for precision medicine, in particular for targeting PKU and other monogenic metabolic diseases...
  62. pmc Novel treatments for rare rheumatologic disorders: analysis of the impact of 30 years of the US orphan drug act
    Thomas Lutz
    Center for Pediatric and Adolescent Medicine Pediatric Rheumatology, and Center for Rare Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
    Orphanet J Rare Dis 11:60. 2016
    ..As a whole group, rare rheumatologic diseases afflict millions of people demanding for effective therapies. Therefore, we analyzed the impact of the US Orphan Drug Act on the development of anti-rheumatic orphan drugs...
  63. pmc Novel Treatments for Rare Cancers: The U.S. Orphan Drug Act Is Delivering-A Cross-Sectional Analysis
    Clemens Stockklausner
    Department of Pediatric Hematology, Oncology, and Immunology, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany
    Oncologist 21:487-93. 2016
    ..Therefore, we systematically analyzed the impact of the U.S. Orphan Drug Act of 1983 on delivery of novel treatments for rare cancers...
  64. doi request reprint Congenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism
    Darius Ebrahimi-Fakhari
    1 The F M Kirby Neurobiology Centre, Department of Neurology, Boston Children s Hospital, Harvard Medical School, Boston, MA, USA 2 Division of Paediatric Neurology and Inherited Metabolic Diseases, Department of Paediatrics, Heidelberg University Hospital, Ruprecht Karls University Heidelberg, Heidelberg, Germany
    Brain 139:317-37. 2016
    ....
  65. doi request reprint Aspartylglucosaminuria: unusual neonatal presentation in Qatari twins with a novel aspartylglucosaminidase gene mutation and 3 new cases in a Turkish family
    Thomas Opladen
    1Department of Pediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital, Heidelberg, Germany
    J Child Neurol 29:36-42. 2014
    ..These 5 cases emphasize that aspartylglucosaminuria is panethnic and may possibly present with prenatal manifestation. Screening for aspartylglucosaminuria should be done in all patients with unexplained psychomotor retardation. ..
  66. doi request reprint Prenatal presentation and diagnostic evaluation of suspected Smith-Lemli-Opitz (RSH) syndrome
    Dorothea Haas
    Division of Inborn Metabolic Diseases, Department of General Pediatrics, University Children s Hospital, Heidelberg, Germany
    Am J Med Genet A 161:1008-11. 2013
    ..For safety reasons and for cost-effectiveness we recommend careful evaluation of history, MSuE3, and clinical presentation before determining sterols in AF...
  67. doi request reprint Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 2. From screening laboratory results to treatment, follow-up and quality assurance
    Peter Burgard
    Department of Paediatrics, University Hospital Heidelberg DE, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
    J Inherit Metab Dis 35:613-25. 2012
    ..g. geneticists, clinical nurse specialists, psychologists). Registry-based evaluation of long-term outcome is as yet almost nonexistent (3 %)...
  68. ncbi request reprint Mevalonate kinase deficiency and autoinflammatory disorders
    Dorothea Haas
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Hospital for Pediatric and Adolescent Medicine, Heidelberg, Germany
    N Engl J Med 356:2671-3. 2007
  69. pmc A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival
    Katharina Rauschenberger
    Institute of Human Genetics, Heidelberg University, Heidelberg, Germany
    EMBO Mol Med 2:51-62. 2010
    ..Therefore alternative therapeutic approaches to an isoleucine-restricted diet are required...
  70. doi request reprint A product of immunoreactive trypsinogen and pancreatitis-associated protein as second-tier strategy in cystic fibrosis newborn screening
    Sophia Weidler
    Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universitat Dresden, Fetscherstraße 74, 01307 Dresden, Germany
    J Cyst Fibros 15:752-758. 2016
    ..We evaluated the IRT×PAP product as second-tier parameter in CFNBS in newborns with elevated IRT...
  71. pmc An Assessment of Publication Status of Pediatric Liver Transplantation Studies
    Thomas Breil
    Pediatric Gastroenterology and Hepatology, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany
    PLoS ONE 11:e0168251. 2016
    ..We therefore assessed the public availability of completed clinical trials in pediatric liver transplantation...
  72. pmc Clinical Research in Vulnerable Populations: Variability and Focus of Institutional Review Boards' Responses
    Bärbel Kästner
    Coordination Center for Clinical Trials KKS, University Hospital Heidelberg, Heidelberg, Germany
    PLoS ONE 10:e0135997. 2015
    ..e., "miscellaneous clinical studies", have no legally mandated timelines for institutional review boards' (IRB) decisions...
  73. pmc Ten Years after the International Committee of Medical Journal Editors' Clinical Trial Registration Initiative, One Quarter of Phase 3 Pediatric Epilepsy Clinical Trials Still Remain Unpublished: A Cross Sectional Analysis
    Anette Lampert
    Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany
    PLoS ONE 11:e0144973. 2016
    ....
  74. doi request reprint Ultra-orphan diseases: a quantitative analysis of the natural history of molybdenum cofactor deficiency
    Konstantin Mechler
    Pediatric Psychopharmacology, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
    Genet Med 17:965-70. 2015
    ..The objective of this study was to quantitate the yet undefined natural history in untreated patients to ultimately benefit knowledge in experimental treatments in the future...
  75. doi request reprint Recurrent acute liver failure due to NBAS deficiency: phenotypic spectrum, disease mechanisms, and therapeutic concepts
    Christian Staufner
    Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, 69120, Heidelberg, Germany
    J Inherit Metab Dis 39:3-16. 2016
    ..Recently biallelic mutations in NBAS were identified as a new molecular cause of ALF with onset in infancy, leading to recurrent acute liver failure (RALF)...
  76. doi request reprint Understanding cerebral L-lysine metabolism: the role of L-pipecolate metabolism in Gcdh-deficient mice as a model for glutaric aciduria type I
    Roland Posset
    Division of Inherited Metabolic Diseases, University Children s Hospital, Heidelberg, Germany
    J Inherit Metab Dis 38:265-72. 2015
    ..In conclusion, L-pipecolate is a major degradation product from L-lysine in murine brain generated by α-deamination of this amino acid...
  77. doi request reprint Emerging role of autophagy in pediatric neurodegenerative and neurometabolic diseases
    Darius Ebrahimi-Fakhari
    1 Division of Inherited Metabolic Diseases, Department of General Pediatrics, Heidelberg Children s Hospital, University Hospital Heidelberg, Ruprecht Karls University Heidelberg, Heidelberg, Germany 2 Institute of Anatomy and Cell Biology, Ruprecht Karls University Heidelberg, Heidelberg, Germany
    Pediatr Res 75:217-26. 2014
    ..To this end, an outlook on novel therapeutic approaches targeting autophagy concludes this review. ..
  78. doi request reprint An international survey of patients with tetrahydrobiopterin deficiencies presenting with hyperphenylalaninaemia
    Thomas Opladen
    Division of Inborn Metabolic Diseases, University Childrens Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
    J Inherit Metab Dis 35:963-73. 2012
    ..The present study summarizes clinical and biochemical findings, current treatment strategies and follow-up in patients with tetrahydrobiopterin (BH(4)) deficiencies...
  79. pmc Efficacy and outcome of expanded newborn screening for metabolic diseases--report of 10 years from South-West Germany
    Martin Lindner
    Centre for Paediatric and Adolescent Medicine, University Heidelberg, Heidelberg, Germany
    Orphanet J Rare Dis 6:44. 2011
    ..However, systematic evaluations of newborn screening programmes are rare, most often only describing parts of the whole process from taking blood samples to long-term evaluation of outcome...
  80. doi request reprint Dynamic changes of striatal and extrastriatal abnormalities in glutaric aciduria type I
    Inga Harting
    Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany
    Brain 132:1764-82. 2009
    ..This may have widespread consequences for the pathophysiological understanding of this disease, long-term outcomes and therapeutic considerations...
  81. ncbi request reprint The molecular basis of phenylalanine hydroxylase deficiency in Croatia
    Johannes Zschocke
    Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany
    Hum Mutat 21:399. 2003
    ..This is the first comprehensive report on PKU mutations in southeastern Europe, adding to the growing bulk of molecular data for population genetic investigations...
  82. ncbi request reprint The diagnosis of mitochondrial HMG-CoA synthase deficiency
    Johannes Zschocke
    Division of Metabolic and Endocrine Diseases, University Children s Hospital, Heidelberg, Germany
    J Pediatr 140:778-80. 2002
    ..We report that the diagnosis can be made by typical laboratory findings (hypoketosis, elevated free fatty acids, normal acylcarnitines, specific urinary organic acids) during acute episodes...
  83. ncbi request reprint Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency: observation of 6 patients in 4 families
    Katharina Mouchegh
    Department of Pediatrics, Klinikum Neukölln, Berlin, Germany
    J Pediatr 150:57-61.e2. 2007
    ..To characterize a new lethal fetal and early postnatal variant of adenylosuccinate lyase (ADSL) deficiency...
  84. doi request reprint Newborn population screening for classic homocystinuria by determination of total homocysteine from Guthrie cards
    Hongying Gan-Schreier
    Department of Pediatrics, Ruprecht Karls University, Heidelberg, Germany
    J Pediatr 156:427-32. 2010
    ..To allow early recognition of cystathionine beta-synthase by newborn screening...
  85. ncbi request reprint Beta-carotene cleavage products after oxidation mediated by hypochlorous acid--a model for neutrophil-derived degradation
    Olaf Sommerburg
    Department of Pediatrics, University of Ulm, Ulm, Germany
    Free Radic Biol Med 35:1480-90. 2003
    ..Our findings may be of biological relevance because beta-carotene CPs are highly reactive and, therefore, potentially toxic...
  86. doi request reprint Molecular neonatal screening for homocystinuria in the Qatari population
    Johannes Zschocke
    Institute of Human Genetics, Ruprecht Karls University, Heidelberg, Germany
    Hum Mutat 30:1021-2. 2009
    ..However, sensitivity for the diagnosis of disorders caused by various mutations is limited even in a homogeneous population such as Qatar...
  87. ncbi request reprint Mevalonate kinase deficiency: enlarging the clinical and biochemical spectrum
    Viola Prietsch
    General Pediatrics, University of Heidelberg, Federal Republic of Germany
    Pediatrics 111:258-61. 2003
    ..Our aim was to describe the clinical picture of adolescent patients with mevalonate kinase deficiency and to expand the clinical and biochemical spectrum of mevalonate kinase deficiency, particularly with regard to HIDS...
  88. ncbi request reprint Biochemical characterization of human 3-methylglutaconyl-CoA hydratase and its role in leucine metabolism
    Matthias Mack
    Institut für Technische Mikrobiologie der Hochschule Mannheim, Germany
    FEBS J 273:2012-22. 2006
    ..The only missense mutation found in MGA1 phenotypes, c.719C>T, leading to the amino acid exchange A240V, produces an enzyme with only 9% of the wild-type 3-MG-CoA hydratase activity...
  89. ncbi request reprint Selective decrease in central nervous system serotonin turnover in children with dopa-nonresponsive dystonia
    Birgit Assmann
    Institute of Child Health, University College London, London WC1N 1EH, UK
    Pediatr Res 52:91-4. 2002
    ..001). We conclude that a significant number of children with DND have reduced CNS serotonin turnover. Treatment with drugs that increase serotonin concentration in the synaptic cleft should be considered in this group of patients...
  90. ncbi request reprint Sepiapterin reductase deficiency: clinical presentation and evaluation of long-term therapy
    Bernard Echenne
    Service de Neuropediatrie, CHU Montpellier, France
    Pediatr Neurol 35:308-13. 2006
    ..Such a widened approach to the diagnostic efforts in early-onset encephalopathy with motor delay during childhood is important, as we have at our disposal a simple and effective treatment...
  91. pmc eIF2B-related disorders: antenatal onset and involvement of multiple organs
    Marjo S van der Knaap
    Department of Child Neurology, Free University Medical Center, Amsterdam, The Netherlands
    Am J Hum Genet 73:1199-207. 2003
    ....
  92. ncbi request reprint Pathophysiology, diagnosis, and treatment of methylmalonic aciduria-recent advances and new challenges
    Friederike Hörster
    Pediatr Nephrol 19:1071-4. 2004
    ..Interdisciplinary research efforts in this field should reveal new pathophysiological links and hopefully provide additional therapeutic approaches...
  93. ncbi request reprint Quantitative acylcarnitine profiling in peripheral blood mononuclear cells using in vitro loading with palmitic and 2-oxoadipic acids: biochemical confirmation of fatty acid oxidation and organic acid disorders
    Andrea Schulze-Bergkamen
    Department of General Pediatrics, University Children s Hospital Heidelberg, 69120 Heidelberg, Germany
    Pediatr Res 58:873-80. 2005
    ..In conclusion, our assay allows biochemical confirmation of a number of FAOD and OAD and could easily be implemented into the confirmatory diagnostic work-up...
  94. ncbi request reprint Evidence that 3-hydroxyglutaric acid interacts with NMDA receptors in synaptic plasma membranes from cerebral cortex of young rats
    Rafael B Rosa
    Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, UFRGS, Rua Ramiro Barcellos, 2600 Anexo, CEP 90035 003, Porto Alegre, RS, Brazil
    Neurochem Int 45:1087-94. 2004
    ..The present study therefore, demonstrates at the molecular level that 3-HGA modulates glutamatergic neurotransmission and may explain previous findings relating the neurotoxic actions of this organic acid with excitotoxicity...
  95. ncbi request reprint Mutations in the cyclic adenosine monophosphate response element of the tyrosine hydroxylase gene
    Marcel M Verbeek
    Department of Neurology and Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Ann Neurol 62:422-6. 2007
    ..Our data suggest that, if no mutations are found in the coding regions of the gene in patients strongly suspected of TH deficiency, the search for pathogenic mutations should be extended to regulatory promotor elements...
  96. ncbi request reprint Bioenergetics in glutaryl-coenzyme A dehydrogenase deficiency: a role for glutaryl-coenzyme A
    Sven W Sauer
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital of Heidelberg, Im Neuenheimer Feld 150, D 69120 Heidelberg, Germany
    J Biol Chem 280:21830-6. 2005
    ..In conclusion, our results demonstrate that bioenergetic impairment may play an important role in the pathomechanisms underlying neurodegenerative changes in glutaryl-CoA dehydrogenase deficiency...
  97. ncbi request reprint Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterozygous MVK carrier possibly influences the phenot
    Silvia Stojanov
    Department of Infectious Diseases Immunology, Children s Hospital, University of Munich, Munich, Germany
    Arthritis Rheum 50:1951-8. 2004
    ....
  98. pmc Secondary mitochondrial dysfunction in propionic aciduria: a pathogenic role for endogenous mitochondrial toxins
    Marina A Schwab
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital Heidelberg, Im Neuenheimer Feld 150, D 69120 Heidelberg, Germany
    Biochem J 398:107-12. 2006
    ....
  99. ncbi request reprint NMDA receptor activation and respiratory chain complex V inhibition contribute to neurodegeneration in d-2-hydroxyglutaric aciduria
    Stefan Kölker
    Division of Metabolic and Endocrine Diseases, University Children s Hospital, Im Neuenheimer Feld 150, D 69120 Heidelberg, Germany
    Eur J Neurosci 16:21-8. 2002
    ..In conclusion, excitotoxicity contributes to the neuropathology of d-2-hydroxyglutaric aciduria, highlighting new neuroprotective strategies...
  100. pmc Isolated 3-methylcrotonyl-CoA carboxylase deficiency: evidence for an allele-specific dominant negative effect and responsiveness to biotin therapy
    Matthias R Baumgartner
    Division of Metabolism and Molecular Pediatrics, University Children s Hospital, Zurich, Switzerland
    Am J Hum Genet 75:790-800. 2004
    ..We show that MCCA-R385S, but not other MCCA missense alleles, reduces the MCC activity of cotransfected MCCA-wild-type allele. Our results suggest that MCCA-R385S is a dominant negative allele and is biotin responsive in vivo...
  101. ncbi request reprint Congenital glutamine deficiency with glutamine synthetase mutations
    Stefan Kölker
    N Engl J Med 354:1093-4; author reply 1093-4. 2006