Identification of mtDNA Mutation in a Pedigree with Gestational Diabetes, Deafness, Wolff-Parkinson-White Syndrome and Placenta accreta

Abstract

Mitochondrial DNA (mtDNA) defects are associated with a number of human disorders. Although many occur sporadically, maternal transmission is the hallmark of diseases due to mtDNA point mutations. The same mutation may manifest strikingly different phenotypes; for example, the A to G substitution at np 3243 was first reported in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (the MELAS syndrome), but is also found in patients with diabetes and deafness. Here we present a case of gestational diabetes, deafness, premature greying, placenta accreta and Wolff-Parkinson-White (WPW) syndrome associated with a mtDNA mutation. Although this is the first report of such an association, study of 27 other patients with WPW syndrome failed to confirm that this mtDNA mutation is a common cause of such pre-excitation disorders.

Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation

“…Reduced heart rate variability, a predictor of cardiovascular death in patients with diabetes [90] and myocardial infarction [91], is frequently seen in MIDD patients without coronary artery disease [86,89]. Other cardiac conduction abnormalities seen in MIDD include Wolff–Parkinson–White syndrome, frequent ventricular extrasystoles and atrial fibrillation [10,51,86,87,92,93]. Although not common [94], m.3243A>G has been identified in subjects previously diagnosed with idiopathic cardiomyopathy [83,84].…”

Diabetes and Mitochondrial Encephalomyopathy

“…9 Women have a higher incidence of pregnancy-related complications such as premature labor and placenta accreta 16 as probably occurred in our patient's maternal grandmother who died of unspecified complications during labor. Metformin, in addition to being less effective, is contraindicated by the high risk of lactic acidosis that these patients have.…”

Diabetes Mellitus with Mitochondrial Gene Mutations in Japan

“…Recent case reports have described cardiomyopathy6 or WPW syndrome8 in diabetic patients with the 3243 mutation. Our study demonstrated a relatively high incidence of cardiomyopathy, WPW syndrome, and sick sinus syndrome in Japanese patients.…”

“…The mitochondrial DNA 3243(A‐G) mutation in the tRNA Leu (UUR) gene originally was reported as a pathological mutation of mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS),1 but is also known to be a major mitochondrial DNA mutation in diabetes mellitus 2–4. The 3243 mutation is also associated with neurosensory deafness,5 cardiomyopathy,6 Alport‐like glomerulopathy,7 and cardiac conduction disturbances 8. Diabetes mellitus with the 3243 mutation is a subtype of diabetes mellitus, referred to as mitochondrial diabetes mellitus9 or maternal‐inherited diabetes mellitus with deafness 10…”