Lysinuric protein intolerance with thymic hypoplasia

Abstract

Lysinuric protein intolerance (LPI; McKusick 222700) is a rare hereditary condition characterized by impaired transport of dibasic amino acids in renal tubuli, intestine, and liver. The increased renal clearance and poor intestinal absorption of these amino acids lead to low plasma levels (Rajantie et al 1980). The patients complain of vomiting, diarrhoea and aversion to protein-rich foods. Hepatosplenomegaly, failure to thrive and hypotonia are the most frequent findings at physical examination. Disturbance of dibasic amino acids uptake by liver cells, and reduced urea-cycle intermediates, arginine and ornithine lead to periodic hyperammonaemia that is responsible for most of the clinical symptoms. Postprandial hyperammonaemia, usually associated with coma, increased urinary excretion of lysine, ornithine and arginine, and low plasma concentrations of these dibasic amino acids, reveals the diagnosis of LPI (Simell 1995).A 35-day-old girl was a normal delivery at term following a normal pregnancy to a 23-year-old woman. The parents are first-degree cousins. Birth weight was 3000g. She had feeding difficulty and generalized convulsions. The previous child died at 24 days from sepsis. Clinical examination revealed hypotonia, depressed newborn reflexes, oral moniliasis and hepatomegaly but no other abnormality.Complete blood count was Hb 8.2g/dl, Hct 28%, white blood cells 5800/ram 3. Urine was negative for ketones and glucose and showed trace proteinuria. Serum electrolyte determinations and liver and renal function tests were normal. C-reactive protein and all cultures were negative. Cranial computed tomographic scan revealed hyperlucent areas of periventricular white matter and increased pericerebral distance. The plasma ammonia level was 255 umol/L (normal range 50-67). Plasma amino acid analysis showed decreased levels of arginine (8 #mol/L, control t01), lysine (2t6 u mol/L, control 309) and omithine (80 g mot/L, control 128). Urine amino acid analysis revealed increased excretion of arginine (7.2/~mol/24h, control 0.1), tysine (81.7,umol/24h, control 8.3) and ornithine (3.4pmol/24h, control 0.8).Daily protein intake was restricted. Double-volume exchange transfusion was carried out seven times and peritoneal dialysis was performed in order to reduce high plasma ammonia levels. She died at 55 days. At autopsy, grossly the thymus was replaced by fibroadipose tissues. Several sections were performed and thymic lobules in fibroadipous tissues were seen in a few. Thus the thymus was markedly reduced in size (hypoplasia). However, its microscopic appearance was normal.About 80 patients with LPI have been reported worldwide, almost half of them in Finland. Nagata and colleagues (1987) reported an 8-year-old girl with LPI with immuno-372