LAUSR

A 5-month-old girl presented to the Emergency Department (ED) because of two self-remitting episodes of loss of consciousness and generalised jerking that lasted 2 min each, separated by a 15-min interval. On admission the baby was afebrile, pale and slightly hyporeactive, but made adequate eye interaction. No vomiting or diarrhoea was reported. Physical examination was unremarkable, and non-dysmorphic, skeletal abnormalities or focal neurological signs were not noted. Her past medical history was unremarkable: Her parents were non-consanguineous and she was delivered after a full-term pregnancy, no perinatal issues were reported. She had been both breast and bottle fed and she had begun her weaning 2 weeks earlier. Her immunisation state was up-todate and she had been assuming daily supplementary vitamin D (400 IU). After her arrival, she presented another generalised seizure; intravenous midazolam (0.1 mg/kg) was administered and the seizure resolved. The baby gained full consciousness but looked unwell. Empirical treatment with intravenous ceftriaxone (100 mg/kg) and acyclovir (1500 mg/m) was started. The interictal electroencephalography did not show epileptic anomalies. Brain computed tomography and magnetic resonance imaging scans were normal. Blood tests, instead, revealed an extremely severe hypomagnesaemia (0.16 mmol/L, normal range 0.75–0.95 mmol/L) associated with a mild hypocalcaemia (HSH) (1.85 mmol/L, normal range 2.18–2.58 mmol/L). Intravenous magnesium sulphate supplementation was started (10 mg/kg/h) and the patient was admitted to the Pediatric Intensive Care Unit (PICU). In the meanwhile, three further seizures occurred. Magnesium blood levels increased to the normal range in 48 h and the girl had no further crisis. Renal magnesium loss was excluded based on the magnesium excretion fraction (1%). No hypercalciuria or nephrocalcinosis was found. An intestinal malabsorption was ruled out by the absence of steatorrhea and by the normal levels of faecal elastases. Magnesium supplementation was eventually shifted from the intravenous to the oral route. Several dose adjustments had been necessary to obtain a stable magnesium level. The final therapeutic schedule consisted of six daily doses of magnesium pidolate (0.75 mg/dose, 0.9 mg/kg/day). Because the clinical picture and blood tests suggested primary hypomagnesaemia, a genetic analysis was performed and showed two mutations in the TRMP6 gene. The former is the known mutation c.2922delA (p.Ala975Glnfs*7), which she inherited from her mother, and the latter, c.5735A>G (p.Tyr1912Cys), is a novel variant, not previously reported in affected or healthy people. This mutation was inherited from her father. Moreover, the c.2922delA (p.Ala975Glnfs*7) involves an amino acid conserved across the species and it is predicted to be pathogenic by different webtools (Mutation Taste, PolyPhen2, PROVEAN, SIFT; J. Craig Venter Institute, La Jolla, CA, USA). Primary hypomagnesaemia with secondary HSH was subsequently diagnosed. One year after, the girl was healthy with a normal psychomotor development and has not presented any further seizure, even if some episodes of tremors and irritability have been reported, all of them concurrent with the detection of low magnesium blood levels.