Lysinuric protein intolerance exhibiting renal tubular acidosis/Fanconi syndrome in a Japanese woman.

Lysinuric protein intolerance (LPI), caused by pathogenic variants of SLC7A7, is characterized by protein aversion, failure to thrive, hyperammonemia, and hepatomegaly. Recent studies have reported that LPI can cause multiple organ dysfunctions, including kidney disease, autoimmune deficiency, pulmonary alveolar proteinosis, and osteoporosis. We report the case of a 47-year-old Japanese woman who was initially diagnosed with renal tubular acidosis (RTA), Fanconi syndrome, and rickets. At the age of 3 years, she demonstrated a failure to thrive. Urinary amino acid analysis revealed elevated lysine and arginine levels, which were masked by pan-amino aciduria. She was subsequently diagnosed with rickets at 5 years of age and RTA/Fanconi syndrome at 15 years of age. She was continuously treated with supplementation of vitamin D3, phosphate, and bicarbonate. A renal biopsy at 18 years of age demonstrated diffuse proximal and distal tubular damage with endocytosis-lysosome pathway abnormalities. Distinctive symptoms of LPI, such as protein aversion and postprandial hyperammonemia were not observed throughout the patient's clinical course. The patient underwent a panel-based comprehensive genetic testing and was diagnosed with LPI. As the complications of LPI involve many organs, patients lacking distinctive symptoms may develop various diseases, including RTA/Fanconi syndrome. Our case indicates that proximal and distal tubular damages are notable findings in patients with LPI. The possibility of LPI should be carefully considered in the management of RTA/Fanconi syndrome and/or incomprehensible pathological tubular damage, even in the absence of distinctive symptoms; furthermore, a comprehensive genetic analysis is useful for diagnosing LPI.

Efficacy of denosumab therapy for a 21-year-old woman with Prader-Willi syndrome, osteoporosis and history of fractures: a case report.

Appropriate management for osteoporosis in adult patients with Prader-Willi syndrome (PWS) has not been established. We report on a 21-year-old woman with PWS, who underwent denosumab treatment for osteoporosis. She presented with fractures and was shown to have very low bone mineral density (BMD), while she had been treated with supplementation of growth hormone for 7-14 years of age and estrogen from 15 years of age. BMD was monitored in the total hip region by dual-energy X-ray absorptiometry. Laboratory tests included bone-specific alkaline phosphatase, urinary type I collagen amino-terminal telopeptide, tartrate-resistant acid phosphatase 5b, 1-alpha, 25-dihydroxyvitamin D3, and parathyroid hormone. BMD and laboratory data were evaluated before and at 4, 8, and 13 months of treatment. After 13 months of denosumab therapy, BMD increased by 4.5%, and bone turnover markers notably improved. No fractures occurred. To the best of our knowledge, this is the first report to describe the clinical outcomes of denosumab treatment for osteoporosis in patients with PWS. Based on our findings, denosumab could represent an effective treatment option for osteoporosis in PWS patients.