Endocrine Abstracts

Background: Hypophosphatasia (HPP) is a rare autosomal recessive metabolic bone disease caused by mutations in the ALPL gene, which encodes tissue non-specific alkaline phosphatase (TNSALP). Reduced TNSALP activity disrupts mineral homeostasis, impairing bone and teeth mineralization. Heterozygous mutations may produce asymptomatic carriers or mild disease through a dominant negative effect. Clinical severity depends on the mutation type and whether it is mono- or biallelic. Perinatal and infantile forms are severe and often fatal. Childhood and adult forms are milder, with bone pain, fractures, bowed legs, premature loss of deciduous teeth, dental caries, muscle weakness, and fatigue. These forms respond to enzyme replacement therapy -Asfotase alfa. Mildest cases, as this case, features are limited to early tooth loss and severe dental caries. Diagnosis is challenging due to HPP’s rarity, non-specific symptoms, and limited clinician awareness.

Case: A 16-year-old female was referred for persistently low ALP noted over several years. Reported a three-year h/o knee, knuckle, lower back pain, and fatigue. Due to extensive dental caries and fillings unusual for her age, dentist suggested medical evaluation. No family history or fractures. Biochemistry showed consistently low ALP (24–26 U/l; ref 60–425) and elevated urinary phosphoethanolamine, with normal calcium, phosphate, vitamin D, and copper studies (excluding Wilson’s disease). Genetics revealed a heterozygous pathogenic ALPL variant (p.Q76R), confirming hypophosphatasia. Management involved multidisciplinary care with regular dental follow-up, optimal oral hygiene, pain control, and ongoing bone health surveillance with imaging as indicated.

Conclusion: HPP should be suspected in young individuals with low ALP, joint pain, and dental complications. Early recognition and multidisciplinary medical-dental care are essential for better long-term outcomes. Bisphosphonates and other antiresorptives should be avoided as these can further impair bone mineralization. Prompt diagnosis prevents misdiagnosis as osteoporosis later in life and avoids further harm to bone and dental health.