Multiple acyl-CoA dehydrogenase deficiency (MADD / Glutaric aciduria type II)

AR; ETFA, ETFB, or ETFDH. The electron transfer flavoprotein (ETF) and ETF-dehydrogenase shuttle electrons from all acyl-CoA dehydrogenases (FAO + branched-chain amino acid catabolism + lysine/tryptophan catabolism) to coenzyme Q. When ETF fails, every dehydrogenase downstream effectively fails too.

Three classical presentations:

• Severe neonatal with congenital anomalies: hypotonia, hepatomegaly, cardiomyopathy, "sweaty feet" odor, polycystic kidneys, facial dysmorphism (high forehead, hypertelorism). Often fatal in the first weeks.
• Severe neonatal without anomalies: metabolic crisis with hypoketotic hypoglycemia and acidosis.
• Late-onset (RR-MADD): lipid-storage myopathy, exercise intolerance, episodic vomiting and weakness. Often riboflavin-responsive (riboflavin is the precursor to FAD, the cofactor for ETF).

Biochemistry:

• Acylcarnitines: pan-elevation (C4 through C18), reflecting blockade of all chain-length dehydrogenases at once
• Urine organic acids: glutaric, ethylmalonic, 2-hydroxyglutaric, and multiple dicarboxylic acids
• "Sweaty feet" odor is shared with isovaleric acidemia (both accumulate short-chain volatile acids)

• Newborn screening acylcarnitine profile shows pan-elevation across short-, medium-, and long-chain species (C4 through C18), the distinguishing pattern
• Urine organic acids: glutaric, ethylmalonic, 2-hydroxyglutaric, and multiple dicarboxylic acids
• Confirmation: molecular testing of ETFA, ETFB, or ETFDH

• Avoid fasting; emergency IV glucose during illness
• Low-fat, low-protein diet with carbohydrate emphasis
• Riboflavin trial in any suspected MADD: dramatic responses in late-onset ETFDH disease
• Carnitine and CoQ10 supplementation are commonly used