Late diagnosis of SLC34A3-related hereditary hypophosphatemic osteomalacia following a low-energy proximal humeral 4-part fracture
Abstract
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare FGF23-independent renal phosphate-wasting disorder caused by biallelic variants in SLC34A3, typically diagnosed in childhood or early adulthood. Delayed recognition in elderly individuals is uncommon, and the clinical features leading to diagnosis in this population remain poorly characterized. We report a case of a 77-yr-old Japanese man with HHRH who remained undiagnosed until advanced age and was identified following a proximal humeral fracture sustained after a low-energy fall. The severity of the fracture, together with his history of multiple previous fractures, prompted biochemical evaluation for secondary causes of skeletal fragility. Biochemical assessment revealed hypophosphatemia with preserved renal function, elevated 1,25(OH)2D3 levels, hypercalciuria, and reduced renal phosphate reabsorption. Intact FGF23 was mildly above the assay reference limit and was not appropriately suppressed in the setting of hypophosphatemia. BMD was in the osteoporotic range at the FN, but it did not distinguish osteoporosis from an underlying mineralization disorder. Genetic analysis identified a homozygous synonymous variant in SLC34A3 (c.942G > C, p.Ala314=) in the context of a characteristic biochemical phenotype consistent with HHRH. Oral phosphate supplementation alone resulted in rapid normalization of serum phosphate levels, without deterioration in renal function or worsening hypercalciuria. This case…
How strong is the evidence?
Evidence Hub reads this as a case report, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Effectiveness of Bisphosphonates and Denosumab on Risk of Vertebral Fractures in Prostate Cancer Patients Under Androgen Deprivation Therapies: A Real-World Prospective Study
- Osteoporosis-related fractures after spinal cord injury: a retrospective study from Brazil
- Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men
- Lack of Association between Vitamin D Insufficiency and Cardiovascular or Fracture Risk: A UK Biobank Study
- Muscle strength and body composition are clinical indicators of osteoporosis
- Incidence of bone protection and associated fragility injuries in patients with proximal femur fractures
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.