ESPE Abstracts

Background: HSH is a rare condition, first described by Paunier et al. (1968). It is an autosomal recessive disorder arising from impaired intestinal absorption of magnesium (Mg) together with renal Mg loss due to a re-absorption defect in the distal convoluted tubule. Mutations in the TRPM6 gene (Chr9q21) (OMIM #607009) have been identified as the underlying genetic defect. A review of 28 affected individuals (21 families) showed median age of diagnosis of 2 months, all but one presenting with seizures. Other modes of presentation include tetany, and associated clinical findings include mental retardation, cardiac arrhythmias, hyperactivity and failure to thrive. We report the only case known to our regional centre over a 20 year period.

Objective/hypotheses/method: Case report and literature review.

Results: A 2 month old Afro-Caribbean infant presented with history of apnoea, limb twitching, drooling of saliva, eye rolling and subsequent floppiness. He was thriving (weight 50th–75th centile) and fully established on formula feed. Examination revealed no dysmorphism, otherwise unremarkable. Initial bloods: Ca 1.59 mmol/l, Phos 2.82 mmol/l, Mg 0.13 mmol/l, ALP 324 IU/l, Vit D 23 μg/l (normal) with PTH 74 ng/l. A standard IV dose of Mg was given with two further repeats to achieve physiologic levels. Renal ultrasound normal; wrist X-ray showed no features of rickets. He was discharged on maintenance oral Mg glycerophosphate (Mg level >0.7 mmol/l). He is now 7 year old and has had five further inpatient admissions for HSH, arising from non-adherence to treatment, the longest interval between each being 30 months. Genetic studies on his TRPM6 gene identified a homozygous splice site mutation, consistent with clinical diagnosis of HSH.

Conclusion: The commonest differential for hypocalcaemia with seizures in an Afro-Caribbean infant in Northern Europe would be vitamin D deficiency. However, atypical biochemical profile, notably hypocalcaemia with severe hypomagnesaemia, should prompt early consideration of the alternative diagnosis of HSH.