SUN-754 Unveiling a Rare Case of Pediatric Hypophosphatasia: Discovery of a Novel ALPL Gene Variant

Abstract Disclosure: M.I. Chiamolera: Consultant of Fleury Group. G.M. Spolador: Fleury Group. J.V. Lima: Consultant of Fleury Group. P. Saddi-Rosa: Fleury Group. R.M. Biscolla: Consultant of Fleury Group. S.S. Maeda: None. Background: Hypophosphatasia (HPP) is a rare disorder caused by variants in the ALPL gene, that encodes the tissue-nonspecific alkaline phosphatase protein (TNSALP), an enzyme involved in the dephosphorylation of a wide range of substrates. Mild HPP is caused by a functional loss of one of the copies of the ALPL gene, leading to autosomal dominant inheritance. Clinical Case: A 8-year-old male patient referred for evaluation of growth delay and low body weight. Initial tests were consistent with HPP: low alkaline phosphatase (ALP) level of 88 U/L (reference range: 142-355 U/L), elevated B6 levels of 75.7 ng/mL (reference range: 8.7 – 27.2 ng/mL). However, the patient showed no signs of rickets. Cranial tomography and skull radiographs suggest a beaten copper appearance. The patient´s father, paternal grandmother and paternal aunt also presented low ALP levels, and the paternal aunt also had short stature. Notably, none of the family members exhibited dental loss. Given the clinical presentation and family history, a genetic panel was requested for further investigation into potential bone fragility disorders. Next-generation sequencing (NGS) identified a novel probably pathogenic variant in the ALPL gene (c.944_946del: p.Val315del) in heterozygous form. Interestingly, the same variant was found in the patient´s father, grandmother and aunt suggesting a possible autosomal dominant inheritance pattern. Conclusion: Further clinical follow-up, including radiographic and biochemical monitoring, along with genetic counseling, is warranted. This case highlights the importance of considering HPP in the differential diagnosis of pediatric patients with growth delay, low stature, and low alkaline phosphatase levels, even in the absence of classic features such as rickets or dental abnormalities. Presentation: Sunday, July 13, 2025