ABSTRACT
3-Hydroxy-3-methylglutaric (HMG) aciduria is a disorder of leucine metabolism that leads to life-threatening illness early in life. Once diagnosed, management, particularly the avoidance of fasting, can be very rewarding. The classic presentation is with a Reye-syndrome-like episode in late infancy (from six months to two years), usually following an intercurrent infection which leads to vomiting or failure to eat. Recurrent episodes of acute illness have been observed particularly in those who presented in the neonatal period. Hepatomegaly is a regular occurrence, and there may be elevation of levels of transaminases in the blood. However, hepatomegaly may be absent especially in the neonatal presentation. Prenatal diagnosis has been accomplished by the analysis of metabolites in maternal urine at 23 weeks of gestation. The enzyme is active in amniocytes. Prenatal diagnosis should be possible by direct measurement of HMG by stable isotope dilution gas chromatography/mass spectrometry of the amniotic fluid.
