SUN-LB089 Mild Form of Childhood Hypophosphatasia: A Novel Mutation

Abstract

Introduction: Hypophosphatasia (HPP) is a rare inherited metabolic bone disorder, caused by loss-of-function mutations within the gene that encodes the tissue nonspecific alkaline phosphatase (TNSALP). Extracellular accumulation of TNSALP natural substrates leads to inhibition of teeth and bone mineralization. Based on age of presentation and presence of skeletal disease, the clinical forms of HPP are perinatal, infantile, childhood, adult and odonto-HPP. The use of enzyme replacement therapy has shown to be highly beneficial specially in the most severe forms. Objective: Report a novel mutation. Clinical Case: A seven-year-old boy with short stature, postnatal growth retardation, development delay and learning disabilities. Background: normal delivery, BW: 2860 g, BL: 47 cm. GA: 39 weeks. Mother: short stature 143.0 cm (-2.9 SDS), bone pain and ALP: 26 UI/L (NR: 40-150) PLP (Pyridoxal 5ˊphosphate): 40 µg/L (NR: 5-50). Physical exam: weight: 15.3 kg (-2.64 SDS), height: 100.5 cm (-3.99 SDS), head circumference: 49.0 cm (-2 SDS), upper segment: 56.2 cm (pc 25). His midparental target height: 162.2cm (-1.55 SDS). Cleft palate, micrognathia, low set ears, wide spaced nipples, mild hyperlaxity, short and wide fingers, clinodactyly of the 5th finger. Tanner stage 1. Laboratory tests showed low serum ALP: 62 UI/L (NR: 135-537 for age and sex), PLP/vitamin B6: 41 µg/L (NR: 5-50), 4 Pyridoxic acid: < 3 µg/L (NR: 3-30). Radiological imaging: hypomineralization in proximal ulna, radius and distal humerus, widening of the first metacarpals with radiolucent zones in all metacarpals and widened metaphysis in lower long bones. Analysis ALPL gene: exon 5 heterozygous variation c.317A>Gp. (Gln106Arg), sequencing Sanger. No ALPL gene deletion or duplication was found. Mother carries the same mutation. Conclusion: This is a novel heterozygous mutation with dominant effect that probably generates a mild form of hypophosphatasia. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.