Endocrine Abstracts

A 29y female presented with an 8y history of hypomagnesaemia. It was noted incidentally when hospitalised with mumps-related pancreatitis. Subsequently symptomatic hypomagnesaemia, with headaches and lethargy, was treated with magnesium glycerol phosphate 4 mg TDS, but she remained symptomatic with occasional need of IV Mg²⁺. It was thought that she was poorly compliant with her oral Mg²⁺ supplements. At presentation to our department for follow-up of her hypomagnesaemia, SeMg²⁺ was low (0.51 mmol/l) despite Mg²⁺ glycerol phosphate 4 mg TDS. Other biochemistry was normal including creatinine, vitamin D, total protein, PTH and cCa²⁺. Urinary Na&K were normal and glucose negative. Urinary Ca²⁺ was low at 1 mmol/24 h (3–5 mmol/24 h). Urinary Mg²⁺ was (inappropriately) normal at 4 mmol/24 h (3–5 mmol/24 h). As the patient appeared to be losing Mg²⁺ from the renal tract, renal imaging with US and CT was performed, showing one large 2.8 cm and four 1.5 cm cysts in the left kidney, while the right was normal. The patient had a bicornate uterus. There was no significant family history. Referral to a geneticist lead to identification of a heterozygous whole gene deletion of HNF1-Beta (renal-cysts-and-diabetes syndrome: RCAD). Neither parent shared this mutation. HNF1b loss-of-function mutations are associated with MODY5, pancreatic insufficiency, renal cysts, hyperuricaemic nephropathy, single functioning kidney, gout, pancreatic atrophy and urogenital deformities (including bicornate uterus). In a paediatric population abnormal antenatal renal US is frequent with Mg²⁺-wasting. HNF1B is important for the expression of FXYD2, which regulates ion transport in the distal convoluted tubule and inactivating mutations in FXYD2 also lead to hypocalciuria and hypomagnesaemia. The differential diagnosis of hypomagnesaemia includes diabetes mellitus, diuretics, platinum-containing chemotherapy, PPIs, EGF-antibodies, alcohol, hypercalcaemia and mutations in paracellin-1 (Mg²⁺-wasting with hypercalciuria due to loss of tight junction, hinders Mg²⁺-reabsorption in ascending loop of Henle), KCNA1 (K⁺-channel which potentiates Mg²⁺-reabsorption via transmembrane electrical potential) and EGF (stimulates Mg²⁺-reabsorption of).