Increased lifelong burden of comorbidities without increased early mortality in hereditary hypophosphatemia: a Danish register study.

Hereditary hypophosphatemia (HH) is a rare diseases characterized by excessive renal phosphate wasting. Hereditary hypophosphatemia presents as rickets and osteomalacia in children, and osteomalacia in adults. Previous studies have suggested an increased burden of comorbidities and higher risk of early death in individuals with HH compared with controls. This study investigates the comorbidities in HH throughout life and their association with survival compared with controls. Possible HH cases were initially identified from the Danish National Patient Register (DNPR) using diagnostic codes for rickets or hypophosphatemia between 1971 and 2019, and the diagnosis was verified by the review of medical files. A total of 120 individuals with verified HH (case population) were matched by gender, birth year, and month with 50 controls per individual with HH, totaling 6000 controls randomly selected from the Danish Civil Registration System. Comorbidity data related to HH were retrieved from the DNPR. The burden of investigated comorbidities was significantly higher in individuals with HH than controls, with multiple conditions diagnosed and at an earlier age. The lifelong risk of arthrosis was significantly higher and diagnosed earlier in individuals with HH (p < .001). By age 50, 31.9% of individuals with HH received their first diagnosis of arthrosis, compared with 4.4% of controls. The lifelong risk of hearing loss was elevated (p < .001), often diagnosed by school age, with a rapid increase by age 60. Additionally, risks of hyperparathyroidism and renal failure were higher (both p < .001), along with increased rates of hypertensive disease (p < .001) and obesity (p = .021), with diagnoses increasing from the third decade of life. However, there was no significant increase in ischemic heart disease risk or overall mortality in HH. Further analysis revealed that comorbidities in HH were not associated with a higher risk of death compared with controls with the same conditions.