Hyperammonemia, Hypocarnitinemia, Rhabdomyolysis, and Pancreatitis in a Patient with Undiagnosed 3-Methylcrotonyl-CoA Carboxylase Deficiency

[Introduction] 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC) is an autosomal recessive disorder of leucine metabolism. The incidence is approximately 1:40,000 and is often diagnosed by newborn screening. 3-MCC deficiency is thought to be a benign condition since most cases are asymptomatic although metabolic decompensation, including hypoglycemia and hyperammonemia associated with hypocarnitinemia, is reported in rare cases. [Case Report] We report a case of a 24-year-old previously healthy male who was hospitalized following a 13-mile hiking trip in harsh conditions due to dehydration, acute onset of emesis, weakness, altered consciousness due to hyperammonemia (217uM), respiratory failure requiring assisted ventilation, rhabdomyolysis with creatine kinase (CK) level of 2,977 units/L and renal failure. High plasma amylase and lipase levels suggesting pancreatitis were noted on admission. Throughout his clinical course, hypocarnitinemia was diagnosed. The patient was treated with carnitine (50mg/kg/d). Plasma acylcarnitine profile and urine organic acids analysis resulted after discharge showing increased plasma C5OH, urine 3-methylcrotonylglycine, and 3-hydroxyisovalerate to establish the diagnosis of 3-MCC deficiency. A low plasma acetylcarnitine was also noted. A homozygous pathogenic variant was identified in the MCCC2 gene (c.994C>T). [Conclusion] While 3-MCC deficiency is considered a benign condition, those not treated with carnitine may have more significant health risks than previously thought. Our case developed hyperammonemia causing altered consciousness as a symptom of 3-MCC deficiency, a previously under-reported complication of this disorder. We also found the patient to have rhabdomyolysis and pancreatitis, which have not been reported to the best of our knowledge. Unexpected life-threatening episodes observed in our case may indicate the need for carnitine supplementation even for asymptomatic individuals with 3MCC deficiency.