Symptom Burden and Clinical Clues in Gitelman Syndrome and Pseudo-Gitelman Syndrome

Gitelman syndrome and pseudo-Gitelman syndrome share overlapping biochemical abnormalities, complicating clinical differentiation and genetic testing allocation. While Gitelman syndrome impairs health-related quality of life (QOL), the comparable burden in pseudo-Gitelman syndrome remains unclear. We compared QOL burden and symptom profiles between individuals with genetically confirmed Gitelman syndrome and those classified as pseudo-Gitelman syndrome.

We evaluated 128 participants aged ≥10 years referred for genetic testing due to suspected Gitelman syndrome (hypokalemia and metabolic alkalosis). Participants were divided into a Gitelman syndrome subgroup (genetically confirmed biallelic SLC12A3 variants; n=66) and a pseudo-Gitelman syndrome subgroup (no disease-causing variants; n=62). Seventy controls were frequency-matched to Gitelman syndrome by age and sex. QOL and clinical manifestations were assessed using a structured 21-item questionnaire covering taste, urinary, muscle, and nonspecific symptom domains. To limit false-positive findings from multiple comparisons, P values were adjusted using the Benjamini-Hochberg procedure; the resulting adjusted P values (q values) <0.05 were considered statistically significant.

Total QOL scores indicated significant and comparable impairment in both the Gitelman syndrome and pseudo-Gitelman syndrome subgroups versus controls (both q <0.001), with no significant difference between the affected groups (q = 0.33). Despite similar overall burdens, specific clinical features differed between the groups. Nocturnal enuresis scores were higher in Gitelman syndrome group than in pseudo-Gitelman syndrome group and controls (both q < 0.001); 50% of Gitelman syndrome participants reported persistence at least until elementary school entry. The taste-related domain was higher in Gitelman syndrome group than in pseudo-Gitelman syndrome group (q = 0.01), but no individual taste item differed after correction.

Individuals with pseudo-Gitelman syndrome experienced QOL impairment comparable to those with genetically confirmed Gitelman syndrome. However, the severity and duration of nocturnal enuresis and overall taste-related symptom burden were prominent descriptive features of Gitelman syndrome. Systematic symptom assessment may contribute to a more comprehensive clinical characterization of individuals with suspected Gitelman syndrome.