The Diagnostic Odyssey in Children and Adolescents With X-linked Hypophosphatemia: Population-Based, Case-Control...

X-linked hypophosphatemia (XLH) is a rare genetic disorder causing renal phosphate wasting, which predicates musculoskeletal manifestations such as rickets. Diagnosis is often delayed.

To explore the recording of clinical features, and the diagnostic odyssey of children and adolescents with XLH in primary care electronic healthcare records (EHRs) in the United Kingdom.

Using the Optimum Patient Care Research Database, individuals aged 20 years or younger after January 1, 2000, at date of recorded XLH diagnosis were identified using Systematized Nomenclature of Medicine Clinical Terms (SNOMED)/Read codes and age-matched to 100 controls. Recording of XLH-related clinical features was summarized then compared between cases and controls using chi-squared or Fisher's exact test.

In total, 261 XLH cases were identified; 99 met the inclusion criteria. Of these, 84/99 had at least 1 XLH-related clinical feature recorded in their primary care EHR. Clinical codes for rickets, genu varum, and low phosphate were recorded prior to XLH diagnosis in under 20% of cases (median of 1, 1, and 3 years prior, respectively). Rickets, genu varum, low phosphate, nephrocalcinosis, and growth delay were significantly more likely to be recorded in cases.

This characterization of the EHR phenotypes of children and adolescents with XLH may inform future case-finding approaches to expedite diagnosis in primary care.