ESPE Abstracts

Background: Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a are autosomal recessive disorder which presents in early infancy with generalized convulsions, or other symptoms related to increased neuromuscular excitability. Several mutations in the TRPM6 gene have been described. Early diagnosis is an effective means of preventing the inevitable neurocognitive sequelae which occur in the absence of appropriate treatment.

Objective: We report on three cases of HSH from one family, with different diagnostic circumstances and neurodevelopmental outcomes.

Family study: The proband is a girl, born to consanguineous parents, who presented aged 4 months with psychomotor delay and convulsions. Investigations (reference range) showed serum calcium 1.6 (2.2-2.6) mmol/l, phosphate 1.45 (1.2-2.6) mmol/l, alkaline phosphatase 270 (70-450) IU/l, parathormone (PTH) 18 (10-65) pg/m, 25 (OH) Vit D 24 (30-80) ng/ml Initial diagnosis was of dietary vitamin D deficiency, given the absence of prophylaxis and the low serum vitamin D level. She was hospitalized again at 6 months with generalize convulsions with fever, and was found to have pneumococcal meningitis, which was successfully treated with antibiotics. The infant was put on Sodium Valproate 30mg/kg/day but her developmental delay progressed and the convulsions persisted, despite addition of a second anticonvulsant. At one year, further investigations showed PTH 18 ng/L), calcium 1.69 mmol/l, phosphate 1.54 mmol/l, and severe hypomagnesemia at 0.22 (0.7-1.1) mmol/l with reduction in fractional magnesium excretion at 0.7 (2-4)%. After administration of intravenous magnesium and calcium followed by high-dose oral magnesium at 45 mg/kg/day (2.28 mg/kg/day) the convulsions ceased. Genetic studies confirmed a missense mutation in the TRPM6 gene. Now aged 10 years, the girl is not attending school, and suffers from a severe movement disorder with learning difficulties. The second child was diagnosed antenatally as an affected homozygote on chorionic villous sampling and was treated with magnesium supplementation immediately after birth. Aged 8 years he is attending normal school, with normal growth and development. The third and fourth children, twins, were unscreened but clinically unaffected. The fifth child, also unscreened, presented at one month with an afebrile convulsion, serum magnesium 0.3 mmol/l and received treatment. Aged 3 years he is not displaying any developmental problems.

Conclusions: Hypomagnesemia should always be considered in infants with persistent and refractory hypocalcemia. Early diagnosis of HSH avoids neurological sequelae and immediate magnesium measurement is recommended in symptomatic hypocalcemia when parents are consanguineous.