Dr Annabel Jones1, Dr I-Lynn Lee1,2, A/Prof Christopher Yates1,3, Dr Dev Kevat1,3,4
1Western Health, Melbourne, Australia, 2Department of Medicine, University of Melbourne, St Albans, Australia, 3Department of Medicine, University of Melbourne, Parkville, Australia, 4Women's and Children's Division, Western Health, St Albans, Australia
Biography:
Annabel Jones is a final year Endocrinology trainee at Western Health with research interests in Obstetric Endocrinology.
Abstract:
Introduction: Glucokinase-maturity-onset diabetes of the young (GCK-MODY) is an autosomal dominant condition whereby inactivating mutations in the GCK gene lead to glucose regulation to a higher set-point (1-2). Outside of pregnancy, treatment is not required and complications are rare. (3-4) In pregnancy, fetal growth in pregnancy and need for glucose-lowering treatment is guided by fetal genotype (5). However, the challenge in managing pregnancies affected by GCK-MODY is that the fetal genotype is rarely known, the uncertainty of which carries both a healthcare and personal psychological burden.
Case: 42F G8P1 presents for management of GCK-MODY diagnosed following previous pregnancy in the setting of personal and family history of early onset ‘T2DM’, frequent severe hypoglycaemic episodes and small for gestational age with insulin treatment. Her daughter and father are subsequently diagnosed with the same variant. This pregnancy, amniocentesis is declined and non-invasive cell free DNA testing (NIPT) is undertaken at 19 weeks (Exeter University, UK) with fetus confirmed to have inherited GCK-MODY. Glycaemic targets are relaxed and fetal growth remains stable with baby born at 25-50th centile with no neonatal hypoglycaemia.
Discussion: Traditionally, fetal genotype is estimated by ultrasound, with accelerating fetal abdominal circumference (>75th percentile) assumed to suggest the fetus has not inherited the maternal mutation (2-3). Ultrasound estimation has poor diagnostic accuracy (sensitivity 53%, specificity 61%) (6) and is burdensome for clinicians and patients. Non-invasive prenatal testing of fetal GCK genotype has recently been developed and has higher diagnostic accuracy (sensitivity 100%, specificity 96%) (6). Additionally, it allows fetal genotype to be inferred earlier in pregnancy (from 13 weeks gestation).
Conclusion: NIPT testing could dramatically improve diagnostic uncertainty associated with the management of GCK-MODY in pregnancy, guide glycemic targets, reduced the economic and personal burden of intensive fetal monitoring and improve perinatal outcomes. Testing availability would be beneficial in Australia.
Keywords
GCK-Mody, Non-Invasive Prenatal Testing, Diabetes in Pregnancy
References
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3. Rudland VL, Price SAL, Hughes R, Barrett HL, Lagstrom J, Porter C, Britten FL, Glastras S, Fulcher I, Wein P, Simmons D, McIntyre HD, Callaway L. ADIPS 2020 guideline for pre-existing diabetes and pregnancy. Aust N Z J Obstet Gynaecol. 2020 Dec;60(6):E18-E52. doi: 10.1111/ajo.13265. Epub 2020 Nov 16. PMID: 33200400
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6. Hughes AE, Houghton JAL, Bunce B, Chakera AJ, Spyer G, Shepherd MH, Flanagan SE, Hattersley AT. Bringing precision medicine to the management of pregnancy in women with glucokinase-MODY: a study of diagnostic accuracy and feasibility of non-invasive prenatal testing. Diabetologia. 2023 Aug 31. doi: 10.1007/s00125-023-05982-9. Epub ahead of print. PMID: 37653058.