Mitochondrial carnitine-acylcarnitine translocase deficiency presenting as sudden neonatal death: Postmortem diagnosis, prenatal exclusion in subsequent pregnancies, and biochemical specificity of the mitochondrial translocase

Abstract

A breast-fed female infant died suddenly in the neonatal period at 31 hours of age with profound macrovesicular fatty infiltration of liver, kidney, and muscle on postmortem examination, suggestive of a defect in fatty acid β-oxidation. Fatty acid and palmitoylcarnitine oxidation studies and direct enzyme study of cultured skin fibroblasts suggested a deficiency in the oxidation of long-chain fatty acids distal to carnitine palmitoyltransferase I and before long-chain acyl–coenzyme A dehydrogenases. Deficient activity of carnitine-acylcarnitine translocase was demonstrated with intermediate levels of activity in the infant’s parents, consistent with autosomal recessive inheritance. Fatty acid oxidation studies showed deficient oxidation of fatty acids at all chain lengths from C 10:0 to C 24:0 , with partially reduced oxidation of C 26:0 fatty acid, indicating the occurrence of a single mitochondrial carnitine-acylcarnitine translocase and demonstrating the requirement in vivo for l -carnitine for mitochondrial transport of all medium- and long-chain fatty acyl moieties. The disorder may have been precipitated in this breast-fed infant by poor initial feeding, fasting stress, and the long-chain triglycerides of human milk. The severity of the disorder prompted prenatal diagnosis, and affected siblings were excluded in two subsequent pregnancies by fatty acid oxidation in cultured chorionic villus cells and amniocytes. (J Pediatr 1997;131:220-5)