Systemic triglyceride storage disease with normal carnitine: a putative defect in long-chain fatty acid metabolism

A 45-year-old Japanese man presented with lipid storage myopathy, fatty liver, cardiomyopathy, vacuolated leukocytes (Jordans' anomaly) and perceptive deafness. His parents were consanguineous and his younger sister was also affected. Histopathological and biochemical studies revealed an abnormal accumulation of triglyceride in muscle, liver, leukocytes, gastrointestinal endothelial cells and cultured skin fibroblasts. On electron microscopy, the vacuoles lacked limiting membranes and were adjacent to the mitochondria. Total and free carnitines in muscle were normal levels. Production rate of 14CO2 or acid-soluble [14C]metabolites from [1-14C]palmitate in the patient's cells was decreased to about 50% of that in control cells, whereas that from [1-14C]butyrate was normal. Long-chain fatty acyl esterase activities in the patient's leukocytes were normal at both pH 4.0 and pH 8.0. Despite the strong suggestion of an impaired metabolism of long-chain fatty acids, there were no evidences of abnormalities in carnitine metabolism or uptake of fatty acids into cells. The disorder is clinically different from defects in carnitine metabolism, defects in the carnitine-acylcarnitine translocase system or in mitochondrial beta-oxidation enzymes. Although the underlying metabolic defect has not been elucidated, this disease seems to be an autosomal-recessively inherited disorder of systemic triglyceride storage, probably due to an impaired regulation of lipolysis and triacylglycerol synthesis.