Journal of Inherited Metabolic Disease

, Volume 30, Issue 1, pp 5–22

Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I)

  • S. Kölker
  • E. Christensen
  • J. V. Leonard
  • C. R. Greenberg
  • A. B. Burlina
  • A. P. Burlina
  • M. Dixon
  • M. Duran
  • S. I. Goodman
  • D. M. Koeller
  • E. Müller
  • E. R. Naughten
  • E. Neumaier-Probst
  • J. G. Okun
  • M. Kyllerman
  • R. A. Surtees
  • B. Wilcken
  • G. F. Hoffmann
  • P. Burgard


Glutaryl-CoA dehydrogenase (GCDH) deficiency is an autosomal recessive disease with an estimated overall prevalence of 1 in 100 000 newborns. Biochemically, the disease is characterized by accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine, which can be detected by gas chromatography–mass spectrometry of organic acids or tandem mass spectrometry of acylcarnitines. Clinically, the disease course is usually determined by acute encephalopathic crises precipitated by infectious diseases, immunizations, and surgery during infancy or childhood. The characteristic neurological sequel is acute striatal injury and, subsequently, dystonia. During the last three decades attempts have been made to establish and optimize therapy for GCDH deficiency. Maintenance treatment consisting of a diet combined with oral supplementation of L-carnitine, and an intensified emergency treatment during acute episodes of intercurrent illness have been applied to the majority of patients. This treatment strategy has significantly reduced the frequency of acute encephalopathic crises in early-diagnosed patients. Therefore, GCDH deficiency is now considered to be a treatable condition. However, significant differences exist in the diagnostic procedure and management of affected patients so that there is a wide variation of the outcome, in particular of pre-symptomatically diagnosed patients. At this time of rapid expansion of neonatal screening for GCDH deficiency, the major aim of this guideline is to re-assess the common practice and to formulate recommendations for diagnosis and management of GCDH deficiency based on the best available evidence.



3-hydroxyglutaric acid


amino acid(s)


apparent diffusion coefficient


Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften


botulinum toxin A




cranial computed tomography


dried blood spots


echo-planar imaging spin-echo


glutaric acid


glutaryl-CoA dehydrogenase


good clinical practice


gas chromatography–mass spectrometry


guideline developmental group


high-performance liquid chromatography




magnetic resonance


magnetic resonance imaging


tandem mass spectrometry


Scottish Intercollegiate Guidelines Network


echo time


repetition time




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Supplementary material

Suppl_Note_Competing_interests.doc (21 kb)
Supplementry Material (21 KB)
Suppl_Note_Contributions_of_authors.doc (22 kb)
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Suppl_Table_10_International_dietary_recommendations.doc (192 kb)
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Suppl_Table_11_Amino_acid_requirements.doc (50 kb)
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Suppl_Table_12_Estimation_of_lysine_intake.doc (44 kb)
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Suppl_Table_13_Preventive_care_Emergency_treatment.doc (32 kb)
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Suppl_Table_14_MRI_standard_protocol.doc (26 kb)
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Suppl_Table_15_Guideline_short_version.xls (29 kb)
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Suppl_Table_1_Evidence_levels.doc (26 kb)
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Suppl_Table_2_Grades_of_recommendations.doc (26 kb)
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Suppl_Table_3_Systematic_literature_review.doc (298 kb)
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Suppl_Table_4_Evidence_base_of_recommendations.doc (249 kb)
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Suppl_Table_5_Incidence_by_NBS.doc (38 kb)
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Suppl_Table_6_C5DC.doc (29 kb)
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Suppl_Table_7_Neuroradiology.doc (27 kb)
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Suppl_Table_8_Probability_estimation.doc (40 kb)
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Suppl_Table_9_False_positive_results_GA_3-OH-GA.doc (28 kb)
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Suppl_Text_1_Encephalopathic_crisis.doc (33 kb)
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Copyright information

© SSIEM and Springer 2007

Authors and Affiliations

  • S. Kölker
    • 1
  • E. Christensen
    • 2
  • J. V. Leonard
    • 3
  • C. R. Greenberg
    • 4
  • A. B. Burlina
    • 5
  • A. P. Burlina
    • 6
  • M. Dixon
    • 7
  • M. Duran
    • 8
  • S. I. Goodman
    • 9
  • D. M. Koeller
    • 10
  • E. Müller
    • 1
  • E. R. Naughten
    • 11
  • E. Neumaier-Probst
    • 12
  • J. G. Okun
    • 1
  • M. Kyllerman
    • 13
  • R. A. Surtees
    • 14
  • B. Wilcken
    • 15
  • G. F. Hoffmann
    • 1
  • P. Burgard
    • 1
  1. 1.Department of General Pediatrics, Division of Inborn Metabolic DiseasesUniversity Children’s HospitalHeidelbergGermany
  2. 2.Department of Clinical Genetics, RigshospitaletCopenhagenDenmark
  3. 3.Biochemistry, Endocrinology and Metabolism, and Neurosciences UnitsInstitute of Child HealthLondonUK
  4. 4.Department of Biochemical and Medical Genetics, Winnipeg Children’s HospitalUniversity of ManitobaWinnipegCanada
  5. 5.Metabolic Unit, Department of PediatricsUniversity Hospital of PadovaPaduaItaly
  6. 6.Department of Neuroscience, Neurological ClinicUniversity HospitalPaduaItaly
  7. 7.Dietetic Department, Great Ormond Street Hospital for Children NHS TrustLondonUK
  8. 8.Academic Medical Centre, Laboratory of Genetic Metabolic Diseases FO-224AmsterdamThe Netherlands
  9. 9.Department of PediatricsUniversity of Colorado Health Sciences CenterDenverUSA
  10. 10.Departments of Pediatrics, Molecular and Medical Genetics, Doernbecher Children’s HospitalOregon Health and Science University, Portland OregonUSA
  11. 11.The National Centre of Inherited Metabolic DisordersChildren’s University HospitalDublinIreland
  12. 12.Department of Neuroradiology, University Hospital MannheimUniversity of Heidelberg Medical SchoolMannheimGermany
  13. 13.Department of Paediatric NeurologyQueen Silvia Children’s HospitalGöteborgSweden
  14. 14.Department of NeurologyGreat Ormond Street Hospital for Children NHS TrustLondonUK
  15. 15.Biochemical Genetics and Newborn Screening Service, The Children’s Hospital at WestmeadUniversity of SydneyWestmeadAustralia

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