Differential Diagnosis: Short-chain acyl CoA dehydrogenase (SCAD) deficiency; Isobutyryl-CoA dehydrogenase (IBDH) deficiency (also referred to as isobutyrylglycinuria (IBG)); Ethylmalonic encephalopathy (EE).
Condition Description: SCAD deficiency is a fatty acid oxidation (FAO) disorder. FAO occurs during prolonged fasting and/or periods of increased energy demands (fever, stress) when energy production relies increasingly on fat metabolism. IBG results from IBDH deficiency. IBDH is an enzyme involved in the degradation of the branched chain amino acid valine. 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 all three conditions, potentially toxic metabolites accumulate.
YOU SHOULD TAKE THE FOLLOWING ACTIONS:
Plasma amino acid analysis which shows increased phenylalanine without increased tyrosine (increased phenylalanine:tyrosine ratio). Urine pterin analysis and red blood cell DHPR assay will identify pterin defects. Consider PAH mutation testing.
Asymptomatic in the neonate. If untreated PKU will cause irreversible mental retardation, hyperactivity, autistic-like features, and seizures. Treatment will usually prevent these symptoms. Pterin defects cause early severe neurologic disease (developmental delay/seizures) and require specific therapy.