TRPM6 is predominantly expressed in the kidney and colon and encodes a protein containing an ion channel domain and a protein kinase domain. It is crucial for magnesium homeostasis and plays important roles in epithelial magnesium transport and the active magnesium absorption. In this study, we present a 70-day-old Iranian female patient from consanguineous parents with hypomagnesemia and secondary hypocalcemia. She presented with seizures 19 days after birth and refractory watery non-bloody diarrhea. She consequently had failure to thrive. Other features included hypotonia, wide anterior fontanel, ventriculomegaly, and pseudotumor cerebri following administration of nalidixic acid. She had severe hypomagnesemia and hypocalcemia which were treated with magnesium and calcium supplementation. Despite initial unstable response to supplemental magnesium, she eventually improved and the diarrhea discontinued. The patient was discharged by magnesium and calcium therapy. At the last follow-up at age 2.5 years, the patient remained well without any recurrence or complication. Genetic testing by whole-exome sequencing revealed a novel homozygous frameshift insertion-deletion (indel) variant in exon 26 of the TRPM6 gene, c.3693-3699del GCAAGAG ins CTGCTGTTGACATCTGCT, p.L1231Ffs*36. Segregation analysis revealed the TRPM6 heterozygous variant in both parents. Patients with biallelic TRPM6 pathogenic variants typically exhibit hypomagnesemia with secondary hypocalcemia and present with neurologic manifestations including seizures. In some patients, this is also complicated by chronic diarrhea and failure to thrive. Long-term complications are rare and most of the patients show a good prognosis with supplemental magnesium therapy.
© 2023. The Author(s) under exclusive licence to The Japan Society of Nephrology.