Objective: Familial hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive disease caused by mutation on transient receptor potential melastatin 6 (TRPM6) gene and characterized by selective magnesium malabsorption. Affected cases are usually diagnosed at infancy with seizures due to hypocalcemia and hypomagnesemia. Irreversible neurological deficits and arrhythmias can be observed without appropriate treatment. We aimed to evaluate the long-term follow-up of six patients with genetically confirmed HSH.
Methods: A total of six patients with HSH, two of whom were siblings, were included in the study. Age at diagnosis, clinical, laboratory and follow-up data on admission were recorded. All the 39 exons of TRPM6 gene and flanking exon-intron junctions from genomic DNA were amplified and sequenced in all cases.
Results: The median follow-up duration was 12.1 years (minimum 7.6, maximum 21.7 years). All cases were diagnosed in infancy. Four different mutations, three of which were not previously identified, were detected in TRPM6 gene. The treatment compliance was good and there was no severe complication in the long-term follow-up of cases. We observed mental retardation, specific learning difficulty and attention deficit / hyperactive disorder as comorbidities.
Conclusion: We identified four different TRPM6 mutations and three of these mutations were newly identified. The long-term prognosis of HSH is good with an early diagnosis and good treatment compliance in our case series. The given long-term follow-up data, prognosis and recently identified mutations in HSH cases will contribute to the increase of knowledge about this rare disease and to prevent negative outcomes.
Keywords: Hypocalsemia; Hypomagnesemia; TRPM6 mutation.