Endocrine Abstracts

Background: Hypophosphatasia (HPP) is a rare metabolic, inherited disease of bone metabolism, caused by loss-of-function mutations within the gene coding for TNSALP, that result in a decrease in serum ALP concentrations and consequent accumulation of ALP substrates outside of the cell, including inorganic pyrophosphate which inhibits bone mineralization. HPP leads to a variety of clinical manifestations across all ages and its prognosis is conditioned principally by the skeletal complications, which generally reflect patient age at presentation.

Case report: We report the case of a 60-year-old woman presenting with chronic kidney disease stage 4 due to progressive nephrocalcinosis and recurrent renal calculi. Starting from the age of 37 yr, when a fracture of distal ulna occurred, the patient had experienced multiple fractures, including bilateral atypical subtrochanteric femoral fractures, and increasing pain, which had resulted in a decrease in her mobility from fully mobile to bed-bound. On physical examination the patient was 145 cm tall and weighed 45 kg. Examination of the lungs, heart and abdomen was unremarkable. ECG and EGA were normal. An ultrasonographic study of abdomen revealed kidneys reduced in volume with irregular profile; bilaterally absent hydronephrosi. Chest radiographs showed severe sclerosis with marked dysmorphism of the scapulae, the humerus and the clavicles. Laboratory evaluation revealed low serum ALP levels (11 UI/l; n.v. 40–150) and high values of Vitamin B6 (33.5 μg/dl; n.v.8.7–27.2), consistently with a diagnosis of HHP. Serum PTH was high (94.20 pg/ml; n.v. 8–76) and 25OH-vitamin D low (9.9 μg/dl; n.v. >30), with total calcium 10.2 mg/dl. Mutation analysis revealed a novel heterozygous mutation in the TNSALP gene (c.1415A>G, p.His472Arg). The mutation identified in this patient’s TNSALP gene have never been previously identified as causing HPP.

Conclusion: We report a novel missense mutation of TNSALP gene, causing late-onset HHP. Up to date over 300 mutations have been identified, which result in a variable loss of function in the enzyme and a consequent decrease in serum ALP concentrations. A clear correlation genotype-phenotype has not been recognized yet.