Work

Heritable metabolic bone disorders: a guide to current genetic testing and clinical management for adult endocrinologists

Year: 2025

Type: article

Abstract: Heritable metabolic bone disorders [including X-linked hypophosphataemia (XLH), hypophosphatasia and osteogenesis imperfecta (OI)] are rare skeletal conditions often presenting in childhood and requiring lifelong multidisciplinary care. Adult endocrinologists frequently find themselves as part of the caring team in an area of medicine experiencing dramatic changes over the past two decades; both diagnostically and therapeutically. Optimal management of skeletal dysplasia requires in-depth understanding of molecular aetiology, genetic testing strategies, and result interpretation; and state-of-the-art management approaches including newer targeted therapies that address fundamental molecular mechanisms. Together, these factors are expanding the reach of genetic testing into mainstream clinical practice. This review will discuss the aetiopathogenesis and clinical burden across the lifespan of three of the more common heritable metabolic bone disorders, outline a modern approach to genetic testing, and discuss current and future therapeutic landscapes informed by recent genomic progress-with the explicit aim of providing practising physicians with a workable and up-to-date approach to the care of individuals with XLH, hypophosphatasia, and OI.

Source: Pathology

DOI: 10.1016/j.pathol.2025.12.001

Authors: Shejil Kumar, Emma L. Duncan, Lisa Hayes, Yemima Berman, Roderick J. Clifton-Bligh, Sunita M.C. De Sousa