MON-494 Infantile Hypophosphatasia Diagnosed in Adulthood: A Case Report

Abstract

Background: Hypophosphatasia (HPP) is a result of loss of function mutations within ALPL gene that encodes for the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). It is characterized by low serum alkaline phosphatase (ALP) activity. To date, HPP was recognized in 500-600 individuals in the United States. Clinical presentation and severity is broad, which can be explained by variable mutations in the TNSALP gene. Elevation of serum pyridoxal-5’-phosphate (vitamin B6), elevation of urinary of phosphoethanolamine (PEA) and finding of a mutation in the ALPL gene support the diagnosis. Asfotase alfa is a recombinant human alkaline phsosphatase that was approved in 2015 for treatment of patients, including adults, with pediatric-onset HPP. Case report: A 56 year old physician presented with a long history of low serum ALP on routine laboratory testing since childhood. During infancy he was diagnosed with craniosynostosis. He had delayed motor milestones and a waddling gait. He was never able to run as a child and he attended high school in a wheelchair. He had severe periodontal disease, lost his first tooth at age 4 and continued to lose his teeth despite excellent dental hygiene care. He has an extensive bone fractures history. He had his first fracture at the elbow at age 6 after he was pulled up by his hands. He developed metatarsal fractures around that time after a fall. He had a metacarpal fracture as an adult with bumping of his hand against the wall. At age 12 he developed hip pain and uveitis. He was diagnosed with ankylosing spondylitis (AS) at age 16 year with a positive HLA B 27. His most recent fracture was at age 45 after he slipped in the shower and sustained a hip fracture. At that time he had a BMD that showed osteoporosis. A bisphosphonate was offered but the patient refused medication as he was worried of the side effects. He has a family history of musculoskeletal disorders. His late mother had a history of low ALP, dental problems, metatarsal fractures and osteopenia. His sister has low ALP and had a low impact radial fracture. His sister’s son who is 18 years old was found to have low serum ALP and was found to have a Z score of -1.5 on BMD. When the patient presented to our clinic, his serum ALP was 22 U/L (n 40-115) and vitamin B 6 was 253 ng/ml (n 2.1-21.7). Genetic testing revealed heterozygous variant in the ALPL gene c.1251T>G (p.Asn417Lys). The patient’s sister and her son were found to have similar mutation of the ALPL gene. The patient was started on treatment with Asfotase alfa. After three months of treatment, the patient reported increased strength and reduced fatigue. Conclusion: We present a rare diagnosis of a 56 year old gentleman who was diagnosed with infantile HPP as an adult. The disease manifested as craniosynostosis, recurrent fractures and periodontal disease. He was started on Asfotase alfa with improvement of symptoms. .