Background: Lysinuric protein intolerance (LPI) is a rare autosomal recessive multisystemic metabolic disorder, caused by defective transport of cationic amino acids at the basolateral membrane of epithelial cells.
Presenting problem: A 14-year-old boy was referred to our clinic for short stature. He was the second child of consanguineous healthy parents. He had previously suffered for 4 fractures occurred secondary to minimal trauma in the upper limbs. He reported that he did not like to eat meat and dairy products. His weight was 30 kg (<3.p), height 135 cm (<3.p), height SDS -3.28, Tanner 2 pubertal stage, bone age 11.5 years, target height 171.5 cm, 1 cm hepatomegaly, no splenomegaly On laboratory; his hemogram, hepatic and renal function tests, serum calcium, phosphorus, and parathormone were normal. His serum alkaline phosphotase was 461 U/l, 25(OH)D 15.7 ng/ml, trigliseride 156 mg/dl, ferritin 336 ng/ml, and LDH 499 U/L, and levels of ammonia were variable. Hypercalciuria or proteinuria was not detected. Lumbar spine DXA Z-score was −3.6 and X-ray revealed vertebral compression fracture. His nutrition patern with osteoporosis causing us to suspect LPI, but plasma and urine concentrations of cationic amino-acids were found normal twice.
Clinical management: His osteoporosis was treated with intravenous pamidronate infusion cycles, vitamin D and calcium supplements. After two years, repeated amino-acid analysis revealed high urinary concentrations of lysine, arginine and ornithine and low blood concentration of lysine compatible with the diagnosis of LPI. The blood was separated for genetic testing and treatment with a low-protein diet and supplementation with citrulline and nitrogen-scavenging drugs was started.
Discussion: The diagnosis of LPI is difficult due to nonspecific clinical features. Classic symptoms of protein intolerance may remain unnoticed because of subconscious avoidance of dietary protein. Over time, patients may present delayed growth, osteoporosis, hepatosplenomegaly, and life-threatening complications such as alveolar proteinosis, haemophagocytic lymphohistiocytosis and macrophage activation syndrome. SLC7A7 is the only gene in which mutation is currently known to cause LPI.
Disclosure: The authors declared no competing interests.