• Nuria Puente-Ruiz, Pablo Docio, María T García Unzueta, Bernardo A Lavín, Ainhoa Maiztegi, Ana Isabel Vega, María Piedra, Leyre Riancho-Zarrabeitia, Fátima Mateos, Domingo Gonzalez-Lamuño, Carmen Valero, and José A Riancho.
• Servicio de Medicina Interna, Hospital U M Valdecilla, Universidad de Cantabria, Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain; Programa post-residencia López-Albo Hospital U M Valdecilla, Servicio Cántabro de Salud, Spain; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Spain.
• J. Intern. Med. 2023 Jun 1; 293 (6): 753762753-762.

BackgroundChronic hypophosphatemia can result from a variety of acquired disorders, such as malnutrition, intestinal malabsorption, hyperparathyroidism, vitamin D deficiency, excess alcohol intake, some drugs, or organ transplantation. Genetic disorders can be a cause of persistent hypophosphatemia, although they are less recognized. We aimed to better understand the prevalence of genetic hypophosphatemia in the population.MethodsBy combining retrospective and prospective strategies, we searched the laboratory database of 815,828 phosphorus analyses and included patients 17-55 years old with low serum phosphorus. We reviewed the charts of 1287 outpatients with at least 1 phosphorus result ≤2.2 mg/dL. After ruling out clear secondary causes, 109 patients underwent further clinical and analytical studies. Among them, we confirmed hypophosphatemia in 39 patients. After excluding other evident secondary causes, such as primary hyperparathyroidism and vitamin D deficiency, we performed a molecular analysis in 42 patients by sequencing the exonic and flanking intronic regions of a panel of genes related to rickets or hypophosphatemia (CLCN5, CYP27B1, dentin matrix acidic phosphoprotein 1, ENPP1, FAM20C, FGFR1, FGF23, GNAS, PHEX, SLC34A3, and VDR).ResultsWe identified 14 index patients with hypophosphatemia and variants in genes related to phosphate metabolism. The phenotype of most patients was mild, but two patients with X-linked hypophosphatemia (XLH) due to novel PHEX mutations had marked skeletal abnormalities.ConclusionGenetic causes should be considered in children, but also in adult patients with hypophosphatemia of unknown origin. Our data are consistent with the conception that XLH is the most common cause of genetic hypophosphatemia with an overt musculoskeletal phenotype.© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

18 keywords...

hide…