Differential Diagnosis: Glutaric aciduria type 2 (GA2), also known as multiple acyl-CoA dehydrogenase deficiency (MADD); Ethylmalonic encephalopathy (EE).
Condition Description: GA2/MADD primarily affects fatty acid oxidation (FAO). FAO occurs during prolonged fasting and/or periods of increased energy demands (fever, stress) when energy production relies increasingly on fat metabolism. GA2/MADD results from ETF/ETF-QO enzyme defects and subsequent inhibition of the proper function of FAO enzymes. EE is a related disorder that seems to be due to a defective mitochondrial matrix protein, the precise function of which is yet unknown. In these conditions, potentially toxic derivatives accumulate.
YOU SHOULD TAKE THE FOLLOWING ACTIONS:
A specific diagnosis is established by plasma acylcarnitine, urine organic acid and acylglycine analysis. Plasma acylcarnitines will show multiple increased acylcarnitines with chain lengths of C4, C5 and higher. Urine organic acids will show a GA2 profile. GA2 can be confirmed with ETF/ETF-QO enzyme assay and gene sequencing. In Ethylmalonic encephalopathy (EE), elevated plasma acylcarnitines will only be C4 and/or C5 and urine organic acids will show increased ethylmalonic acid and isovalerylglycine. The diagnosis is confirmed by ETHE1 gene sequencing.
GA2/MADD often presents in the neonate with poor feeding, marked lethargy, and facial and renal dysmorphism. Laboratory tests will reveal hypoketotic hypoglycemia, metabolic acidosis and hyperammonemia. Milder forms may present in childhood or later. EMA encephalopathy presents in infancy with developmental delay, diarrhea and petechiae.