ESPE Abstracts (2021) 94 P1-20

ESPE2021 ePoster Category 1 Bone A (10 abstracts)

A novel TRPM6 variant (c.3179T>A) causing familial hypomagnesemia with secondary hypocalcemia

Meghna Chawla 1 , Girish Bhardwaj 2 & Atul Patil 3

1Ruby Hall Clinic Group of Hospitals, Pune, India; 2Base Hospital, Delhi, India; 3Ruby Hall Clinic, Pune, India

Familial hypomagnesemia with secondary hypocalcemia (FHSH) is a rare autosomal recessive disorder (OMIM# 602014) caused by mutations in the gene encoding TRPM6 (Transient receptor potential melastatin 6) on chromosome 9q22. This channel causes epithelial absorption of magnesium in the colon and renal distal convoluted tubule. Fewer than 100 cases have been reported in literature. A four year old girl had presented to us with tetany lasting for 30 minutes. Detailed history revealed that she had repeated episodes of convulsions, the first being when she was 3 days old, which was a generalized tonic - clonic convulsion lasting for around 2 minutes. Tetany like episodes consequently were observed at the age of 1 yr and 3 yrs. All the previous episodes subsided with intravenous calcium gluconate. She was developmentaly normal and there was no family history of similar episodes or consangunity. A basic workup revealed hypocalcemia 7.1 mg/dl (8.8 -10.8 mg/dl) and hypomagnesemia 0.5 mg/dl (1.7-2.3 mg/dl). Fractional excretion of magnesium was <1.4% (NR: 2-4%). Serum PTH was normal 54.2 (12.0 – 65.0 pg/ml). Complete blood count, C- reactive protein, Serum electrolytes, arterial blood gases and renal function test were normal. In view of the severe hypomagnesemia, magnesium sulphate infusion and intravenous calcium gluconate was started. On Day 2 of treatment serum magnesium levels increased to 1.4 mg/dl and serum calcim levels normalized. Genetic evaluation: Clinical Exome Sequencing was done which revealed a homozygous nonsense variation in exon 17 of the TRPM6 gene that results in a stop codon and premature truncation of the protein at codon 717. Our case revealed a novel TRPM6 gene variant c.3179T>A (p.Arg717Ter). As far as we know this homozygous variant has not been reported in the 1000 genomes database and has a minor allele frequency of 0.0007% in the gnomAD database. The in silico prediction of the variant is damaging by MutationTaster2. We considered the variant found in the patient to be pathogenic, especially associated with the clinical manifestations at presentation. She was discharged on 20mg/kg per day of oral magnesium supplements and at the end of a six month follow up maintains a magnesium level at the lower end of normal range. She remains normal clinically and developmentally. Thus, although rare, FHSH should be considered in any child presenting with refractory hypocalcemic seizures and severe hypomagnesemia, as early diagnosis and treatment can result in a normal physical and neurological development.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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