GeneDx :: Tests :: Glutaric Aciduria II (GAII) or Multiple Acyl-CoA Dehydrogenase Deficiency (MADD)

301-519-2100 • FAX 301-519-2892 • 207 PERRY PARKWAY GAITHERSBURG, MD 20877

Glutaric Aciduria II (GAII) or Multiple Acyl-CoA Dehydrogenase Deficiency (MADD)

ETFA, ETFB and ETFDH genes

Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) or Glutaric Aciduria II (GAII) is an extremely rare autosomal recessive disorder that can result from deficiency of the alpha or beta subunits of electron transfer flavoprotein or its dehydrgenase ETF:ubiqinone oxidoreductase (ETF-DH or ETF:QO). Defects in any of these genes may lead to a range of clinical phenotypes from mild to severe, depending upon the mutation. Three clinical phenotypes for GAII have been described. Type I presents as a life-threatening disorder during the neonatal period with tachypnea, dyspnea, profound acidosis, severe hypotonia and convulsions. Hepatomegaly, hypoketotic hypoglycaemia, hyperammonemia, sweaty-sock like odor and congenital anomalies including renal cystic dysplasia, heart abnormalities, central nervous system malformations, facial dysmorphism, rocker bottom feet, and abnormalities of the external genitalia may also be present. Type II presentation is similar to Type I without the congenital anomalies, while a Type III presentation occurs later with intermittent episodes of vomiting, hypoglycemia, and metabolic acidosis during infancy or episodic muscular weakness and pain during adulthood along with progressive myopathy. Recurrent panceatitis has also been reported with abdominal symptoms. Sequence analysis of the ETFA, ETFB and ETFDH genes has identified 2 mutations in approximately 75-87% of patients with GAII.

Mutation analysis of the ETFDH, ETFB and ETFA genes is performed on genomic DNA from the submitted specimen using bi-directional sequence analysis of the coding exons and the corresponding intron/exon boundaries. If clinically indicated, for patients who have a single mutation identified after full sequencing of all three genes, or when otherwise appropriate, GeneDx will perform reflex deletion/duplication testing (ExonArrayDx) at no additional charge. Mutations found in the first person of a family to be tested are confirmed by repeat analysis using sequencing, restriction fragment analysis, or another appropriate method. Testing for the ETFDH, ETFB and ETFA genes can be ordered sequentially, if specifically requested, or all 3 genes can be analyzed simultaneously if a more rapid turnaround time is needed. If other studies have determined which subunit of the genes is defective, sequencing of the appropriate gene should be ordered. Carrier testing and prenatal diagnosis is available once the mutation in the family has been defined.

Information Sheet, including prices and CPT codes
Consent Document
Genetic Test Sample Submission Form (Test Requisition Form) including Payment Options

Ethylmalonic-Adipicaciduria, EMA, Glutaric Aciduria IIA, ETFA Deficiency, Glutaric Aciduria IIB, ETFB Deficiency, Glutaric Aciduria IIC, ETFDH Deficiency, electron transfer flavoprotein, ETF, electron transfer flavoprotein dehydrogenase, ETF-DH, respiratory chain, urine organics, acylcarnitine profile, newborn screening.