ESPE Abstracts (2018) 89 P-P2-073

A Novel Mutation in Phka2: Idiopathic Ketotic Hypoglycaemia May Represent Mild Gsdixa

Anne Benner Flejsborga,b, Klaus Brusgaardc, Carsten Pedersend, Anja L Frederiksenc & Henrik T Christesena,b,e


aDepartment of Clinical Research, Odense, Denmark; bHans Christian Andersen Children’s Hospital, Odense, Denmark; cDepartment of Clinical Genetics, Odense, Denmark; dDepartment of Paediatrics, Kolding, Denmark; eOPAC Odense Pancreas Centre, Odense, Denmark


Background: Idiopathic ketotic hypoglycaemia (IKH) is an exclusion diagnosis and the most common cause of hypoglycaemia in childhood. Glycogen Storage disease (GSD) type IX comprises one quarter of all GSD’s. GSDIXa, encoded by PHKA2, is the most frequent subtype.

Objective: To investigate whether IKH may be undiagnosed GSDIXa.

Methods: Hospital file review and next generation sequence 29 gene GSD-panel.

Results: From 8 month’s age, a 6 year-old Caucasian boy diagnosed with IKH had recurrent fasting hypoglycaemia down to 1.8 mmol/l; B-ketones 1.7 mmol/l. He had no dysmorphic features, height +0.4SD. Normal investigations included liver enzymes, hepatic ultrasound, synachten test, i.m. glucagon test, p-insulin suppression during hypoglycaemia, urine metabolic screening and p-carnitine profile. A subnormal peak GH at stimulation tests prompted GH treatment age 2.5–3 years with no effect on hypoglycaemia. Brain MRI showed white matter lesions in the right hemisphere possibly due to hypoglycaemia. Hypoglycaemia symptoms in childhood were reported in the mother, maternal grandmother and the mother’s two sisters and one of their daughters. The grandmother’s monozygotic twin died 3-month-old for unknown reason. The patient’s 4-year-old brother had hypoglycaemia down to 2.8 mmol/l. Family history prompted reevaluation of the IKH diagnosis on suspicion of X-linked hypoglycaemia. GSD panel identified a novel, maternal PHKA2 mutation, c.4C>G, p.(Arg2Gly), classified as a variance of unknown significance.

Conclusion: IKH and GSDIXa may clinically overlap, why GSDIXa may be under/un-diagnosed. We hypothesize that IKH may represent milder variants of GSD. GSD gene panel and family testing is encouraged in IKH to improve precision of treatment and prognosis, and to diagnose affected family members.

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