Year: 2025
Type: article
Abstract: Disclosure: S. Rajoo: None. N. Mohd Makhatar: None. S.D. Simanchalam: None. Hypophosphatasia (HPP) in adult is a rare genetic metabolic bone disorder. Detection of this disorder is low in adult population as its symptoms are nonspecific and often mistaken for other medical problems. For the first time, we encountered a 33 year old lady who had incidental osteoporosis on bone mineral density (BMD) on a medical check up (Z score femoral neck: -4.1 , Z score total lumbar: -2.9). Retrospective inquiry revealed that she has vague lower back pain on prolonged sitting position and multiple dental cavities requiring repeated filling. She is small built with low body mass index of 16 kg/m2 with regular menses. There were no signs of malnourishment and no history of fractures in the past. However, her alkaline phosphatase (ALP) was low at 24 U/L (normal range, 35-105 U/L) with normal calcium, phosphate, magnesium, total vitamin D, thyroid and parathyroid hormones. Bone turn over markers such as total procollagen type1 amino-terminal propeptide (P1NP), B-CrossLaps (B-CTx) and bone ALP were normal, inferring her bones were not excessively remodeling but rather demineralizing. Images of her spine failed to reveal any chondrocalcinosis. Entertaining the possible diagnosis of HPP, Pyridoxal-5’-phopsphate (natural substrates of tissue non-specific ALP - TNSALP) levels were also within normal range, 83 nmol/L (35-100). Finally, genetic testing was conclusive for heterozygous pathogenic variant c.984_986del (p.Phe328del) of ALPL gene. Adults with HPP maybe true adult-onset type HPP or survivors of milder forms of childhood-onset HPP. HPP may often be missed in adulthood as it’s not as debilitating and fatal as in infancy or childhood. Patients less often seek medical attention for mild myalgia. Reduced mineralization on basic radiograph imaging usually prelude to a BMD examination. The HPP International Working Group has proposed diagnostic criteria for adult HPP: major criteria include ALPL gene variant(s), elevation of natural substrates of TNSALP, atypical femur fractures, and recurrent metatarsal stress fractures, whereas minor criteria consist of poorly healing fractures, chronic musculoskeletal pain, early atraumatic loss of teeth, chondrocalcinosis and nephrocalcinosis. Persistently low ALP with 2 major, or 1 major and 2 minor criteria establishes the diagnosis of HPP. Our patient fulfills low ALP, musculoskeletal pain and poor dentation, and further supported with gene sequencing. The similar low BMD presentation of osteoporosis may be mistakenly treated with anti resorptives which will further hamper bone formation and bone healing. Treatment for HPP is with enzyme replacement, Asfotase Alpha. However, treatment and duration of treatment in asymptomatic adults or milder disease is not entirely established and requires further research especially in the reproductive female population. Presentation: Sunday, July 13, 2025
Source: Journal of the Endocrine Society
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,255
OpenAlex ID: W7093367688
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