Endocrine Abstracts

Background: Hypophosphatemic rickets, mostly of the X-linked dominant form caused by pathogenic variants of the PHEX gene, poses therapeutic challenges with consequences for growth and bone development and portends a high risk of fractions and poor bone healing, dental problems and nephrolithiasis/nephrocalcinosis (1). Children with hypophosphatemic rickets present poor growth, deformities of weight-bearing limbs such as genu varum or valgus, a ‘rachitic rosary’ involving the costochondral junctions, or enlargement of wrist, knees, or ankles among other symptoms. Family history may lead to detection of genetic forms prior to demonstration of rickets. (2)

Case report: 14-year-old woman, referred from pediatrics due to growth retardation since early childhood. Family history of mother with pathological short stature of unstudied origin. Analyzes show persistently low phosphorus with low 25 OH vitamin D and elevated alkaline phosphatase, normal IGF1 and IGFP3. Karyotype 46XX. Bone age delayed 2 and a half years for chronological age. On physical examination, discrete genu varus, with short stature of 143 cms (-2.87 SD). Given the suspicion of hypophosphatemic rickets, a genetic study is requested: The patient is a heterozygous carrier of the variant c.1843A>C (p.Thr615Pro) in the PHEX gene, which is later confirmed in her mother. Currently undergoing treatment with oral phosphorus and cholecalciferol, she remains asymptomatic, with normalization of analytical parameters and with good clinical evolution.

Conclusions: Hypophosphatemic rickets/osteomalacia represent a set of rare disorders with many genetic and acquired causes and potential in long-term complications for children and adults, and diminishing physical function and quality of life. Conventional treatment with phosphate supplements and pharmacologic doses of active vitamin D may require the addition of growth hormone and calcimimetics. New biological therapeutics, including FGF23 targeting monoclonal antibodies or recombinant receptor blockers, are being developed and becoming available. Lastly, identification of genetic mutations associated with hypophosphatemia syndromes has contributed to our understanding of the pathogenesis and potential treatment of hypercalciuria, nephrocalcinosis, and renal stones disease.