7154 Adult Hypophosphatasia With Heterozygous Missense Mutations In ALPL Gene

Abstract Disclosure: A.S. Chaugule: None. Y. Cervelo: None. S. Dhillon: None. D. Tuncay: None. We present a case of a male in his third decade of life discovered to be a carrier of the genetic mutation associated with hypophosphatasia during routine pre-conception genetic screening. Genetic analysis revealed a heterozygous pathogenic missense variant which is c.979TC, p.F327L in the ALPL gene. A retrospective chart review after genetic diagnosis revealed that he had an alkaline phosphatase (ALP) level at 35 Units/Liter (U/L) which was considered normal as the reference range of the lab test was 31-120 U/L in 2019. The patient also had a childhood history of severely weakened enamel, dental cavities, and renal stones. After the genetic diagnosis, he was referred for a bone density scan which revealed osteoporosis of the lumbar spine. On review of symptoms, he complained of diffuse musculoskeletal pain. Current investigations revealed a low alkaline phosphatase level of 32 (U/L) and high 24-urine calcium excretion. He was started on vitamin D3 supplements and hydrochlorothiazide which led to improvement in his 24-urine calcium excretion. As an adopted individual, no family history was available. Based on laboratory and clinical findings he qualified for starting therapy with Asfotase Alfa. Hypophosphatasia is a rare and highly heterogeneous disease condition with varied mutations in the ALPL gene resulting in multiple phenotypes. Numerous studies have studied the importance of diagnosing hypophosphatasia based on clinical features, laboratory testing, radiographic findings, and family history. Fragility fractures along with age and sex-adjusted serum total ALP levels are important clinical and laboratory features respectively, promptly leading to a clue in the diagnosis of adult hypophosphatasia. ALP levels should always be corrected to the age and sex of the patient and levels less than 40 U/L should prompt a workup for hypophosphatasia. The diagnosis of hypophosphatasia for our patient was delayed due to the absence of a history of fractures, a previously recorded normal ALP and an unknown family medical history. Diagnostic criteria have been formulated to help aid the diagnosis of hypophosphatasia in childhood and include various childhood clinical manifestations and laboratory features. Diagnosis can often be missed given the wide range of clinical features. This case underscores the importance of genetic screening in symptomatic children with frequent dental problems for identifying carriers of hypophosphatasia, especially in the case of an unknown family history. Timely diagnosis and management can help improve a patient’s quality of life. Presentation: 6/2/2024