ESPE Abstracts (2022) 95 P1-456

1University Hospitals Bristol and Weston, Bristol, United Kingdom; 2University Hospitals Plymouth, Plymouth, United Kingdom

Background: The association between HNF1A-MODY and vascular complications including stroke has previously been identified in adults but to date there have been no reported paediatric cases published.

Description: We present the case of an Eritrean 13-year-old girl, who was admitted with an acute ischaemic stroke, on a background of Diabetes Mellitus (Presumed Type 1) diagnosed the previous year. Aside from being on multiple dose injections (MDI) of basal-bolus insulin at 0.9Units/kg/day, she had no other regular medications. There was a history of vitiligo (longstanding, with negative adrenal antibodies) with no history of acanthosis nigricans or clinical features of insulin resistance. On acute presentation, she was normoglycaemic (7.2mmol/L), normotensive (122/90mmHg) with normal body habitus (weight 46kg) and no other known cardiovascular risk factors (non-smoker, normal lipid profile). She was confirmed to have an anterior spinal artery infarct and multiple small cerebellar infarcts on MRI and underwent extensive investigations to identify the cause. In view of her acute presentation on a background of negative islet cell autoantibodies at diagnosis and first degree family history of diabetes, a broader screen for mitochondrial and monogenic diabetes was performed. This identified a missense mutation in the HNF1A gene, (Ch12:g.121432011G>A). Of note, her father was mosaic for the mutation with 7% of his cells affected. She was diagnosed with Maturity Onset Diabetes of the Young (MODY) HNF1A, and her diabetes treatment was altered accordingly, enabling her to be switched from MDI insulin to sulphonylureas.

Discussion: Glycaemic control correlates poorly with cardiovascular risk in HNF1A-MODY, instead the increased risk may be related to wider metabolic dysfunction. HNF1A variants have been associated with changes to cholesterol homeostasis, lipid profile and endothelial factor dysfunction. Populations of Black African Heritage have an increased risk of stroke from a younger age, and a recent study identified the HNF1A variant (rd55931441) as a significant stroke-associated locus in this population. This clinical case supports the current evidence that single nucleotide polymorphisms at the HNF1A locus may be implicated in metabolic dysregulation and cerebrovascular injury, particularly in young black patients. Further genomic research is needed in this patient cohort. Aggressive cardiovascular risk reduction and primary prevention from adolescence may be implicated.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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