RATE-DEPENDENT DISTAL RENAL TUBULAR-ACIDOSIS AND CARNITINE PALMITOYLTRANSFERASE-I DEFICIENCY

An infant girl presented with recurrent episodes of Reye-like syndrome associated with hypoketosis and plasma carnitine levels in the high-n ormal range. A liver biopsy revealed massive macrovesicular steatosis. Ketogenesis was absent after a long-chain triglyceride loading test; in contrast, the medium-chain triglyceride loading test resulted in a brisk rise in plasma ketone concentration. Carnitine palmitoyltransfer ase I deficiency was demonstrated in cultured skin fibroblasts. Hypogl ycemia was only found once in the neonatal period. Renal carnitine han dling was normal except for a higher renal threshold for free carnitin e. Mild, persistent metabolic acidosis was a constant feature, even du ring periods between metabolic decompensation. Evaluation of the renal acidification capacity showed a failure to acidify the urine during s pontaneous acidosis but increased acid excretion and a normal decrease of urinary pH after acid loading. Also, a small difference between ur ine and blood Pco(2) was found after bicarbonate administration. This acidification defect can best be explained as an abnormality in distal tubular H+ secretion: a rate-dependent distal tubular acidosis. It is speculated that long-chain acylcarnitines, substances that cannot be formed by carnitine palmitoyltransferase I-deficient patients, play an essential role in renal acid-base homeostasis.