ESPE Abstracts

Background: Hypercalcaemia in infants may reach extreme levels due to hyperparathyroidism, subcutaneous fat necrosis, or vitamin D intoxication. Normal values for p-parathyroid hormone and p-calcitriol prompt search for other causes.

Methods: Hospital file evaluation, case report.

Results: A 5½-months-old Caucasian girl of non-consanguineous healthy parents was referred due to weight loss with escalating total p-calcium to 3.86 mmol/L, p-ionized calcium 1.85 mmol/L (pH corrected). P-parathyroid hormone was <0.4 pmol/L, p-25-hydroxyvitamin D₃ 93 nmol/L, calcitriol 60 pmol/L, urine calcium/creatinine ratio >6/0.9. Mild hypercalcaemia and transient elevation of ALT was noted months before. Emergency treatment included i.v. fluids, bisphosphonate, steroids, calcitonin and potassium citrate.

A rapidly increasing p-lactate to 21 mmol/L led to severe acidosis with respiratory exhaustion and intubation. Blood glucose was 3.9 mmol/l upon arrival, but non-ketotic severe hypoglycaemia (p-glucose 0.1 mmol/L) occurred the following day, promptly treated with i.v. glucose. Oral feeding was discontinued. Further evaluation showed severely enlarged, hyperechoic liver, increased p-ALT (127 U/L), GGT ( 202 U/L), p-triglycerides (10.4 mmol/L), LDL cholesterol (1.8 mmol/L) and p-pyruvate (230 mcmol/L at p-lactate 2.0 mmol/L); mildly enlarged kidneys with nephrocalcinosis grade 1-2; and urinary loss of potassium, magnesium, phosphate and albumin in addition to calcium, all requiring i.v. and/or oral substitution.

P-growth hormone and cortisol did not suggest hormone insufficiency. Urine metabolic screening showed severe ketosis; p-amino acids and acylcarnitine profile were normal for the dietary circumstances. A rapid trio whole exome scan identified compound heterozygous mutations (c.508C>T, p.Arg170Ter and c.562G>C, p.Gly188Arg) in G6PC, confirming the diagnosis of glycogen storage disease type 1a (GSD1a).

The i.v. glucose demand increased to 17.5 mg/kg/min at 12 days after admission, where a hypoglycaemia test showed inappropriately elevated p-insulin of 41 (ref. 18-173) pmol/L at p-glucose 3.0 mmol/L, p-C-peptide 1234 (ref. 400-1600) pmol/L, confirming hyperinsulinaemic hypoglycaemia.

The patient was referred to the national centre for GSDs. Dietary treatment with continuous tube feeding with soy-based formula, dextrose and i.v. glucose to keep p-glucose in the range of 5-7 mmol/L succeeded to control the hyperlactataemia. The i.v. glucose demand gradually decreased and bolus meals could be initiated.

Conclusion: GSD1a with metabolic crisis can lead to severe hypercalcaemia despite suppressed p-parathyroid hormone and normal p-calcitriol. Hyperinsulinaemic hypoglycaemia can complicate the treatment during the metabolic crisis.