ESPE Abstracts

Introduction: Lysineuric protein intolerance (LPI) is a rare autosomal recessive disorder caused by mutations in the SLC7A7 gene, which impairs the intestinal, renal and hepatic absorption of basic amino acids (lysine, arginine, ornithine). Children with LPI may present with protein avoidance, growth retardation, hepatosplenomegaly and osteoporosis. Here, we present two cases diagnosed with LPI due to short stature, with one case involving growth hormone (GH) treatment experience.

Case 1: A 2-year-9-month-old boy was evaluated for short stature. Physical examination revealed a height of 72.5 cm (-4.5 SD), weight of 9 kg (-4.6 SD) and testicular volume of 2/2 ml. The patient was born weighing 3 kg, with consanguineous parents. Screening for chronic diseases was negative. Karyotype was 46,XY and genetic tests for SHOX, Russell-Silver, 3M, and Short Syndrome were normal. Growth hormone stimulation tests (GHST) showed insufficient peak GH responses (clonidine: 7.7 mcg/L, L-dopa: 9.1 mcg/L). Bone age was 2 years and GH therapy was initiated. In the first year of treatment, the patient experienced a growth velocity (GV) of 7.2 cm (0.6 SDS). However, due to elevated ferritin and LDH levels and hepatosplenomegaly, GH therapy was discontinued. Genetic analysis revealed a homozygous c.536G>A variant in the SLC7A7 gene, confirming a diagnosis of lysinuric protein intolerance (LPI). Consequently, a protein-restricted diet and citrulline supplementation were initiated. GH therapy was retried to address the patient's short stature, but it failed to achieve a sufficient growth velocity. The discontinuation of follow-up by the patient contributed to this outcome, though the treatment is still ongoing.

Case 2: A 7-month-old boy was referred for short stature. Following a viral infection, elevated transaminase and ferritin levels and hepatosplenomegaly were noted. Urine organic acid analysis and genetic testing (SLC7A7 gene c.1098dupT homozygous) confirmed LPI. He was started on a protein-restricted diet, citrulline, and arginine. The patient was born at 36 weeks, weighing 3200 grams, with third-degree consanguinity between parents. Physical examination revealed a height of 78 cm (-1.34 SD), weight of 9.2 kg (-1.77 SD), and O-bain deformity. At 5 years, the patient's height was 100.5 cm(-2.2 SD) and weight 15 kg (-1.71 SD), with sufficient GHST response.

Conclusion: In cases of unexplained severe short stature with elevated ferritin and LDH levels and hepatosplenomegaly, LPI should be considered. There are reports of both sufficient and insufficient GHST responses in LPI patients in the literature. GH therapy has been attempted alongside disease-specific treatments in these cases.

Keywords: Lysineuric Protein Intolerance, Short Stature, Growth Hormone Therapy