FAMILIAL SUDDEN CHILD DEATH IN A FAMILY WITH PSEUDO-DOMINANT DICARBOXYLIC ACIDURIA AND HYPOKETOTIC HYPOGLYCEMIA

Abstract

A family is described in which the father and three (and probably all four) children had a decreased capacity for the oxidation of medium-chain fatty acids resulting in a defective ketogenesis. The 4th child died at the age of 16 months during an episode of hypoketotic hypoglycemia (plasma glucose 0.7 mmole/l; 3-hydroxybutyrate 1.7 mmoles/1). Previously the child had always been in good health. Medium-chain fatty acids accumulated in the patient's plasma; the urinary organic acid profile showed large amounts of dicarboxylic acids and fatty acid conjugates such as hexanoylglycine, octanoylcarnitine, and octanoylglucuronide. The activity of medium-chain acyl-CoA dehydrogenase in an autopsy liver sample was only 15% of the mean control. The first child had died at the age of 19 months under similar conditions. When subjected to a 17 h fast the father and the 2nd and 3rd child, but not the mother, accumulated octanoic, decanoic and cis-4-decenoic acids in their plasma.Their urinary organic acid profile resembled that of the deceased 4th child, but excretions were at a lower level. Measurement of [14-C]-octanoate degradation in cultured fibroblasts revealed low values for the father and the two ‘healthy’ children as compared to the controls. It is suggested that a -partial- deficiency of medium-chain acyl-CoA dehydrogenase may lead to life-threatening illness when gastrointestinal abnormalities eventually lead to a severe depletion of the glycogen stores. Careful monitoring of at-risk patients is indicated under these circumstances.