Endocrine Abstracts

Introduction: Hypophosphatasia (HPP) is a rare metabolic bone disorder characterized by deficient activity of alkaline phosphatase, resulting from pathogenic variants in the ALPL gene. The clinical spectrum can range from perinatal lethal forms to mild adult-onset presentations. Adult HPP is often underdiagnosed, as symptoms overlap with common musculoskeletal and rheumatological conditions. Early recognition is critical, as inappropriate use of anti-resorptive therapies can exacerbate disease and enzyme replacement therapy (asfotase alfa) may offer benefit in selected cases.

Case Presentation: A 31-year-old woman, an intensive care unit (ICU) nurse, was referred for evaluation of chronic musculoskeletal pain. She reported lower back pain with early morning stiffness since adolescence, worsening in 2016. HLA-B27 was positive, though MRI of the lumbar spine and sacroiliac joints (2020) revealed no evidence of inflammation. Non-steroidal anti-inflammatory drugs (ibuprofen, etoricoxib) provided minimal relief. She also described intermittent left shoulder pain since 2012, exacerbated during acute illness, and left knee pain with swelling after prolonged walking. Her past history included a finger fracture, loss of three adult teeth, and frequent dental chipping. She denied childhood skeletal deformities or gait abnormalities. Intermittent tinnitus was reported. Family history revealed rheumatoid arthritis in her mother and stomach cancer in her father. No known familial bone disease was reported. She was a non-smoker, non-drinker, and lived with her partner. During a COVID-19 infection in 2022, routine laboratory testing identified low alkaline phosphatase (ALP) at 6 U/l (reference range: 30–130 U/l). Review of past results confirmed persistently low ALP values (6–17 U/l) over the preceding five years. Serum calcium, magnesium, zinc, copper, liver and renal function, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were consistently normal. Genetic testing confirmed a pathogenic ALPL variant, establishing the diagnosis of hypophosphatasia. She was subsequently referred to a rare bone disease clinic. Management included a referral to pain team, physiotherapy and genetic counselling. She reported that a herbal preparation (Devil’s Claw) provided superior pain relief compared with pharmacological options.

Discussion: This underscores the importance of considering HPP in patients with chronic pain as treatment modalities could make a considerable difference, Enzyme replacement, alfa asfotase though primarily indicated in pediatric-onset disease, evidence suggests possible symptomatic and radiological improvement in adults. Antiresoptives, especially bisphosphonates, should be avoided due to increased risk of AFF. Genetic counselling is essential given AD inheritance. Options for family members and reproductive planning include non-invasive & invasive prenatal testing and pre-implantation genetic testing.