ESPE Abstracts (2019) 92 P3-29

Extreme Hypercalcaemia: Watch for Glycogen Storage Disease Type 1a with Hyperinsulinism

henrik christesen1, Rasmus G Nielsen1, Allan M Lund2, Arlen A Cananguez3, Anders J Schou1

1Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark. 2Center for Inherited Metabolic of Rare Diseases, Dept. of Clinical Genetics and Dept. of Paediatrics and Adolescent Medicine, Copenhagen, Denmark. 3Dept. Paediatrics, Southwest Jutland Hospital, Esbjerg, Denmark

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.

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