1196 PLASMA AND MUSCLE CARNITINE DEFICIENCY IN RENAL FANCONI SYNDROME

Abstract

Children with renal Fanconi syndrome (FS) fail to reabsorb water, amino acids, glucose, electrolytes, and other small molecules including carnitine. In 21 FS patients (18 with cystinosis, the most common identifiable cause of FS in children), the mean urinary fractional excretions of free and acyl carnitines were 32% and 27%, resp., compared with control values of 3% and 5%, resp. (N=6). Plasma free carnitine was 11.6±4.0 (SD) nmol/ml in FS and 42.0±9.0 in controls (p<0.001). The plasma carnitine deficiency in FS was independent of age, cysteamine therapy, and renal glomerular function. The liver did not appear functionally carnitine-deficient in FS, since 2 patients exhibited a normal, 5 to 10-fold increase in β-hydroxybutyrate and acetoacetate after a 24-hour fast. In 2 other patients with cystinosis and plasma carnitine deficiency, muscle free carnitines were 8.5 and 13.1 nmol/mg noncollagen protein (4 controls 19.2±2.5); total muscle carnitines were 11.8 and 13.3 (controls 24.8±7.5). The greatest relative decrease in muscle carnitine was in the short chain acyl carnitine fraction. One muscle biopsy in a cystinosis patient revealed an increase in lipid droplets. A muscle biopsy in another patient showed a large increase in lipid droplets, small vacuoles, occasional “ragged-red” fibers, a slight increase in connective tissue, and variation in muscle fiber size. These myopathic changes, consistent with carnitine deficiency, may be amenable to therapy with L-carnitine replacement.