Endocrine Abstracts

Introduction: Ornithine transcarbamylase deficiency (OTCD) is a urea cycle disorder that causes the accumulation of ammonia, which can lead to neurocognitive problems in patients¹. Here we report a 21-year-old man who was diagnosed with OTCD during investigation for secondary osteoporosis.

Case: The patient applied to the Endocrinology department complaining of widespread muscle-joint pain, shortening in height, nausea/vomiting attacks followed by protein-rich nutrition and weight loss (8 kilograms in 5 months). His personal history was otherwise unremarkable. He had a brother with osteoporosis diagnosed of 17 while being investigated for avascular necrosis of the hip. Bone mineral density measured with dual X ray absorptiometry showed a lumbar Z score-3.4 and a femur neck Z score of -2.2 concluded. Scoliosis was observed on X ray and no fracture is detected computed tomography. No hypogonadism was detected in laboratory tests performed for secondary osteoporosis. 1 mg dexamethasone suppression test was normal. Celiac markers, ANA and the enzymatic test for Gaucher’s disease were negative. Serum calcium, phosphorus, magnesium and alkaline phosphatase, 24-hour urinary calcium, parathormone, and 25OH vit-D values and anterior pituitary hormones, were found to be within the normal limits as well as abdominal ultrasonography. The patient had suffered learning difficulties since childhood, protein intolerance and the development of nausea and vomiting attacks after consuming foods rich in protein. Serum ammonia test revealed hyperammonemia. Genetic tests showed hemizygote c.206A>G (p.Gln69Arg) mutation in OTC gene. The patient is given a protein poor diet which resulted in significant improvement with clinical symptoms and a decrease in nausea and vomiting.

Discussion: Osteoporosis was reported previously in lysinuric protein intolerance which is a member of the family of urea cycle defects². In the present case, OTCD may be a possible cause of osteoporosis. Although the mechanism is not fully understood the low-protein content in diet, the decrease in amino acid activity can cause decreased collagen synthesis, leading to a decrease in bone density³.

References: 1. Gropman AL, Summar M, Leonard JV. Neurological implications of urea cycle disorders. J Inherit Metab Dis. 2007 Nov;30(6):865-79. doi: 10.1007/s10545-007-0709-5. Epub 2007 Nov 23.

2. Posey JE, Burrage LC, Miller MJ, Liu P, Hardison MT, Elsea SH, et al. Lysinuric protein intolerance presenting with multiple fractures. Mol Genet Metab Rep. 2014;1:176–83. https://doi.org/10.1016/j.ymgmr.2014.03.0048.

3. Parto K, Penttinen R, Paronen I, Pelliniemi L, Simell O. Osteoporosis in lysinuric protein intolerance. J Inherit Metab Dis. 1993;16(2):441–50.