ESPE Abstracts (2022) 95 P1-236

ESPE2022 Poster Category 1 Diabetes and Insulin (86 abstracts)

A novel homozygous mutation in the Glycerol-3-Phosphate Dehydrogenase 1 gene combined with a heterozygous mutation in the Glucokinase Regulator gene associated with hyperglycaemia, hypertriglyceridaemia and non-alcoholic fatty liver in a 17 year old woman

Georgia Avrami 1 , Mojgan Drasdo 2 , Steffen Neuber 2 , Norbert Jorch 1 & Eckard Hamelmann 1


1Department of Paediatric Endocrinology, Children’s Center Bethel, University Hospital OWl, University Bielefeld, Bielefeld, Germany; 2Bioscientia, Department of Human Genetics, Ingelheim, Germany

Background: Hyperglycaemia combined with hypertriglyceridaemia and non-alcoholic fatty liver, not directly related to Type 1 diabetes mellitus (T1DM,) is a rather uncommon metabolic disorder in children, which often evades early and accurate diagnosis. Even though considerable progress has been made in identifying some of the genes involved, the molecular basis of conditions presenting with hypertriglyceridaemia, deranged liver function and insulin resistance remains undefined.

Case presentation: We present a case report of a 17-year-old female with initial findings of hyperglycaemia, hypertriglycaemia and non-alcoholic fatty liver. An elevated glycosylated haemoglobin (HbA1c) was documented. Due to the absence of T1DM autoantibodies in repeated blood assays, the diagnosis of maturity-onset diabetes of the young (MODY) was suspected. Nevertheless, all relevant genetic tests conducted to verify this assumption remained inconclusive. The patient was subsequently placed on metformin without sufficient improvement. Aiming to at least achieve normalization of blood glucose, adjuvant diet and lifestyle changes were advised. Further testing using next-generation sequencing analysis (NGS) for familiar hypertriglyceridemia and hypercholesterolemia revealed the presence of the missense variant c.895G>A in the Glycerol-3-Phosphate Dehydrogenase 1 gene (GPD1), resulting in the amino acid substitution p.(Gly299Arg). Furthermore, the heterozygous variant c.307G>A in the Glucokinase Regulator gene (GCKR) was detected, resulting in the amino acid substitution p.(Val103Met). To the best of our knowledge and following extensive research of online databases, this constitutes the first case of an adolescent patient with a homozygous c895G>A mutation in the GPD1 gene presenting with hypertriglyceridaemia, hyperglycaemia and insulin resistance. The heterozygous mutation c.307G>A in the GCKR gene represents the second such reported case.

Discussion: The presence of hyperglycaemia and hypertriglyceridaemia combined with non-alcoholic fatty liver in paediatric patients, in the absence of T1DM antibodies, should raise suspicion of GPD1 and GCKR mutations. Early detection of such patients through genetic screening allows prompt disease recognition and specific treatment, whilst minimizing disease progression.

Keywords: Type 1 diabetes mellitus, hyperglycaemia, hypertriglyceridaemia, non-alcoholic fatty liver, MODY, GPD1, GCKR.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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