Two cases of hereditary hypomagnesaemia with secondary hypocalcaemia and 4 novel mutations on TRPM6 gene / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the clinical,biochemical and genetic features of hereditary hypomagnesaemia with secondary hypocalcaemia.Methods Two boys came from different Chinese families.They were hospitalized at the Peking University First Hospital between 2014 and 2016 at the age of 9 years and 1 year and 2 months because of epilepsy and psychomotor retardation.Clinical investigation,laboratory examination,and medical imaging were performed for the etiological study.Whole-genome sequencing was used for the genetic analysis of the patients.Mutations of TRPM6 gene were confirmed by means of Sanger sequencing.Results Patient 1 presented with recurrent seizures and psychomotor retardation from the age of 3 months.Vision loss and psychomotor regression were noticed from the age of 9 years,accompanied with hypertension.Serum magnesium and total calcium were significandy decreased to 0.13-0.15 mmol/L and 1.43-2.00 mmol/L,respectively in patient 1.Serum potassium was reduced to 1.85-3.25 mmol/L.Blood parathyroid hormone was also decreased.On the TRPM6 gene of patient 1,2 novel non-sense mutations,c.2771G ＞ A (p.Trp924Ter) and c.115C ＞ T (p.Gln39Ter) were identified.Patient 2 presented with seizures and psychomotor retardation at the age of 2 weeks.Both of his serum magnesium (0.17-0.35 mmol/L) and serum total calcium (1.32-1.34 mmol/L) were significantly decreased.Blood parathyroid hormone was decreased.Two novel mutations (c.1239G ＞ A,p.W413X and c.146G ＞ A,p.C49Y) were found in the TRPM6 gene of patient 2.Severe hypomagnesaemia,hypocalcaemia and TRPM6 gene mutations confirmed the diagnosis of hereditary hypomagnesaemia with secondary hypocalcaemia in the 2 patients.After the large-dose supplement of magnesium sulfate,progressive clinical improvements were observed in the 2 patients.However,because of the severe brain damage,patient 1 still had psychomotor retardation.Patient 2 completely recovered.Conclusions Hereditary hypomagnesaemia with secondary hypocalcaemia is a severe inherited metabolic disease.Early diagnosis and large-dose magnesium supplement are the key to the good prognosis of the patients.In this study,2 Chinese children with the clinical onset of epilepsy and psychomotor retardation are reported.The diagnosis is made by way of blood biochemical assay and gene analysis.Four novel mutations on their TRPM6 gene are identified.