Long-term outcome of isobutyryl-CoA dehydrogenase deficiency diagnosed following an episode of ketotic hypoglycaemia

摘要

Isobutyryl-CoA Dehydrogenase Deficiency (IBDD) is an inherited disorder of valine metabolism caused by mutations in ACAD8 . Most reported patients have been diagnosed through newborn screening programmes due to elevated C4-carnitine levels and appear clinically asymptomatic. One reported non-screened patient had dilated cardiomyopathy and anaemia at the age of two years. We report a 13?month old girl diagnosed with IBDD after developing hypoglycaemic encephalopathy (blood glucose 1.9?mmol/l) during an episode of rotavirus-induced gastroenteritis. Metabolic investigations demonstrated an appropriate ketotic response (free fatty acids 2594?μmol/l, 3-hydroxybutyrate 3415?μmol/l), mildly elevated plasma lactate (3.4?mmol/l), increased C4-carnitine on blood spot and plasma acylcarnitine analysis and other metabolic abnormalities secondary to ketosis. After recovery, C4-carnitine remained increased and isobutyrylglycine was detected on urine organic acid analysis. Free carnitine was normal in all acylcarnitine samples. IBDD was confirmed by finding a homozygous c.845C?>?T substitution in ACAD8 . The patient was given, but has not used, a glucose polymer emergency regimen and after ten years' follow-up has had no further episodes of hypoglycaemia nor has she developed cardiomyopathy or anaemia. Psychomotor development has been normal to date. Though we suspect IBDD did not contribute to hypoglycaemia in this patient, patients should be followed-up carefully and glucose polymer emergency regimens may be indicated if recurrent episodes of hypoglycaemia occur.