NEWBORN SCREENING

[Elevated C5-DC Acylcarnitine]

Glutaryl-CoA Dehydrogenase Deficiency (GA-1)

 

Differential Diagnosis: Glutaric Acidemia (GA-1). 

Condition Description: GA-1 is caused by a defect of glutaryl-CoA dehydrogenase which limits metabolism of glutaryl-CoA, resulting in increased glutaric acid (toxic) and its metabolites. 

MEDICAL EMERGENCY - TAKE THE FOLLOWING IMMEDIATE ACTIONS:

  • Contact family  IMMEDIATELY to inform them of the newborn screening result
  • Consult with pediatric metabolic specialist
  • Evaluate the newborn for macrocephaly and muscle hypotonia, initiate confirmatory/diagnostic testing as recommended by metabolic specialist
  • Refer to metabolic specialist to be seen as soon as possible, but not later than three (3) weeks
  • Educate family about diagnostic possibilities, complexity of diagnostic work-up and the possibility of neurodegenerative crisis with an intercurrent infectious illness
  • IMMEDIATE treatment with IV glucose is needed for intercurrent infectious illness
  • Report findings to state newborn screening program (Carleigh Soule at 307-777-6297) 

Diagnostic Evaluation: Urine organic acid analysis will reveal elevated glutaric acid and 3-hydroxyglutaric acid which should be ordered promptly and is often diagnostic. If urine organic acids don’t confirm the diagnosis, the metabolic specialist will consider analyzing glutarylcartinine in urine and 3-hydroxyglutaric acid in blood and CSF, enzyme assay in fibroblasts, and molecular analysis of the GCDH gene. 

Clinical Expectations: The neonate with Glutaric Acidemia Type I is usually macrocephalic but otherwise asymptomatic. Later signs include metabolic ketoacidosis, failure to thrive, and sudden onset of dystonia and athetosis due to irreversible striatal damage. With appropriate treatment, 60-70% of patients will not suffer neurodegenerative disease. 

Additional Information: (Click on the name to take you to the website) 

Genetic Home Reference                                Wyoming Department of Health
http://ghr.nlm.nih.gov                                    http://www.health.wyo.gov  

Gene Tests                                                   Colorado Newborn Screening
http://www.genetests.org/                             http://www.cdphe.state.co.us  

New England Consortium                                 American Academy of Pediatrics
http://www.childrenshospital.org/                     http://pediatrics.aappublications.org/

 

 
www.acmg.net
 

For Algorithm: http://www.acmg.net/resources/policies/ACT/Visio-C5-DC(4-29-06).pdf