OSTEOPOROSIS IN LYSINURIC PROTEIN INTOLERANCE

Lysinuric protein intolerance (LPI) is an autosomal recessive disease characterized by defective transport of cationic amino acids. Patients have an increased incidence of fractures and their skeletal radiographs show osteoporosis. The aim of the study was to characterize the osteopenia in LPI. Twenty-nine Finnish LPI patients (age range 3.7-44.4 years) were screened for parameters of bone metabolism. Morphometric analysis of bone was carried out in specimens of 9 patients. Collagen synthesis was studied with cultured skin fibroblasts (4 patients) and collagen fibril sizes (3 patients) were measured using electron microscopy. Most histological bone specimens (8/9) showed osteoporosis. Osteomalacia was excluded. Routine clinical laboratory tests were unrevealing. The concentrations of free hydroxyproline and type Ill procollagen N-propeptide in serum and the urinary excretion of hydroxyproline were increased in almost all patients during their growth and in about half of adult patients. Collagen synthesis in LPI fibroblast cultures was significantly decreased compared with that in age-matched controls at 5 (p < 0.01), 14 (p < 0.01) and still at 30 years (p < 0.01), whereas no difference was observed at the age of 44 years (p = N.S.). Osteoporosis in LPI might reflect defective matrix protein synthesis caused by protein deprivation and deficiency of cationic amino acids. Increased collagen turnover can also contribute to the osteoporosis.