Hypomagnesemia is underestimated in children with HNF1B mutations

Background Hypomagnesemia in patients with congenital anomalies of the kidneys and urinary tract or autosomal dominant tubulointerstitial kidney disease is highly suggestive of HNF1B -associated disease. Intriguingly, the frequency of low serum Mg 2+ (sMg) level varies and is lower in children than in adults with HNF1B mutations that could be partially due to application of inaccurate normal limit of sMg, irrespective of age and gender. We aimed to re-assess cross-sectionally and longitudinally the frequency of hypomagnesemia in HNF1B disease by using locally derived reference values of sMg. Methods Fourteen children with HNF1B -associated kidney disease were included. Control group comprising 110 subjects served to generate 2.5th percentiles of sMg as the lower limits of normal. Results In both controls and patients, sMg correlated with age, gender, and fractional excretion of Mg 2+ . In girls, sMg concentration was higher than in boys when analyzed in the entire age spectrum ( p < 0.05). In HNF1B patients, mean sMg was lower than in controls as compared with respective gender- and age-specific interval ( p < 0.001). Low sMg levels (< 0.7 mmol/l) were found in 21.4% of patients at diagnosis and 36.4% at last visit, which rose to 85.7% and 72.7% respectively when using the age- and gender-adjusted reference data. Similarly, in the longitudinal observation, 23% of sMg measurements were < 0.7 mmol/l versus 79.7% when applying respective references. Conclusions Hypomagnesemia is underdiagnosed in children with HNF1B disease. sMg levels are age- and gender-dependent; thus, the use of appropriate reference data is crucial to hypomagnesemia in children.