Dysregulation of calcium metabolism in type 1 myotonic dystrophy

Patients with type 1 myotonic dystrophy (DM1) have a higher incidence of hypercalcaemia compared with the general population. The nature and effects of dysregulated calcium metabolism underpinning this phenomenon have not been fully characterised.

To determine the characteristics of dysregulated calcium metabolism in patients with DM1 and its association with bone mineral density.

A retrospective review of medical records of patients with DM1 attending a DM clinic at Logan Hospital, Brisbane, Queensland, between 2005 and 2018 and who had concurrent serum assays performed of corrected serum calcium, 25 hydroxyvitamin D, parathyroid hormone (PTH) and phosphate and for whom results were available for estimated glomerular filtration rate, bone mineral densitometry tests and urinary calcium clearance to creatinine clearance ratio (UCCR).

Forty-four patients with DM1 (22 females, 22 males) were reviewed of whom 14 (32%) had elevated corrected serum calcium and inappropriate PTH. Another 10 patients (23%) had raised PTH with normocalcaemia. Eighteen of 19 (94.7%) patients with hypercalcaemia or high PTH level completed 24-h urinary calcium. All had UCCR ≤0.02. Twelve patients had UCCR <0.01. Seven of 44 (16%) had low 25 hydroxy vitamin D. All patients had normal estimated glomerular filtration rate. None was osteoporotic.

One in three patients with DM1 was hypercalcaemic with unsuppressed PTH. Their clinical features and biochemical pictures resemble those of familial hypocalciuric hypercalcaemia (FHH) and raises the possibility that impaired activity of calcium-sensing receptors, due to abnormal splicing of the calcium-sensing receptor messenger RNA in DM1, causes a FHH-like syndrome ('pseudo-FHH of DM1').