Antenatal diagnosis of a fetal glucokinase gene mutation determines if maternal hyperglycaemia requires treatment during pregnancy — ASN Events
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Antenatal diagnosis of a fetal glucokinase gene mutation determines if maternal hyperglycaemia requires treatment during pregnancy (#97)

Victoria L Carleton 1 2 , Ali J Chakera 3 4 , Sian Ellard 3 4 , Jencia Wong 1 2 , Dennis K Yue 1 2 , Jason Pinner 2 , Andrew T Hattersley 3 4 , Glynis P Ross 2
  1. The University of Sydney, Sydney, NSW, Australia
  2. Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  3. University of Exeter, Exeter, UK
  4. Royal Devon and Exeter Hospital, Exeter, UK

Background: A heterozygous mutation in the glucokinase (GCK) gene causes a mild, asymptomatic form of monogenic diabetes, known as Maturity Onset Diabetes of the Young (GCK-MODY or MODY2) [1]. Women with GCK mutations are often first identified during pregnancy and are, therefore, almost invariably diagnosed as having gestational diabetes (GDM). However, the standard management of GDM, particularly the implementation of intensive glycaemic control, can adversely affect the fetus of a woman with a GCK mutation [2]. Identification of GCK mutations in the GDM population is therefore extremely important.

In pregnancy, treatment of maternal hyperglycaemia due to a GCK mutation is primarily influenced by fetal genotype. An affected fetus, in the setting of untreated maternal hyperglycaemia, will have a normal birth weight. However, birth weight is increased by 550-700g if the fetus is unaffected [2,3]. Insulin is indicated if the fetus is unaffected. However, if the fetus has inherited a GCK mutation, fetal growth will potentially be reduced if maternal euglycaemia is achieved, so insulin is not recommended [2,4]. Fetal genotype is usually not known antenatally.

We describe two cases of maternal hyperglycaemia in pregnancy due to GCK mutations and demonstrate how knowledge of the fetal genotype guides management of maternal hyperglycaemia.

Cases: We present two pregnant women with heterozygous GCK mutations causing hyperglycaemia sufficient to warrant treatment (Case 1: c.1340G>A,p.Arg447Gln; Case 2: c.370G>A,p.Asp124Asn). In both women, DNA from chorionic villus sampling, performed following high-risk aneuploidy screening, revealed the fetus had inherited the GCK mutation. Thus, maternal hyperglycaemia was not treated. Both offspring had normal birth weights and no peri-partum complications.

Conclusions: We report two pregnant women with GCK mutations, for whom, knowledge of fetal genotype directly changed management of maternal hyperglycaemia. Given that universal genetic testing is not currently practicable, pregnancy-specific screening criteria for GCK testing in GDM is required.

  1. Byrne MM, Sturis J, Clement K, Vionnet N, Pyeyo ME, Stoffel M, Takeda J, Passa P, Cohen D, Bell GI, Velho G, Froguel P, Polonsky KS. Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. J Clin Invest 1994;93:1120-
  2. Spyer G, Macleod KM, Shepherd M, Ellard S, Hattersley AT. Pregnancy outcome in patients with raised blood glucose due to a heterozygous glucokinase gene mutation. Diabet Med 2009;26:14-18.
  3. Hattersley AT, Beards F, Ballantyne E, Appleton M, Harvey R and Ellard S. Mutations in the glucokinase gene of the fetus results in reduced birth weight. Nat Genet 1998;19:268-270.
  4. Spyer G, Hattersley AT, Sykes JE, Sturley RH and Macleod KM. Influence of maternal and fetal glucokinase mutations in gestational diabetes. Am J Obstet Gynecol 2001;185:240-241.