3-Hydroxy-3-methylglutaryl-CoA lyase deficiency, commonly known as HMG-CoA lyase deficiency, is a rare inborn error that affects ketogenesis and leucine catabolism. Symptoms usually appear in the first year of life and include metabolic acidosis with hypoketotic hypoglycemia, hyperammonemia, abnormal liver function tests, vomiting and hypotonia. Other signs are hepatomegaly, macrocephaly, and less frequently microcephaly, seizures, acute pancreatitis, dilated cardiomyopathy and arrhythmia. Abnormal cerebral white matter foci on MRI has also
been reported. Without treatment, rapid progression to coma and death or permanent neurological damage may occur. With treatment, many patients do well; however recurrent metabolic decompensation continues to occur especially with prolonged fasting or intercurrent illness. This disorder is fatal in approximately 20% of cases with the symptoms becoming milder after childhood.