%0 Journal Article
%T Diabetic Dead-in-Bed Syndrome: A Possible Link to a Cardiac Ion Channelopathy
%A Jonathan R. Skinner
%A Renate Marquis-Nicholson
%A Alix Luangpraseuth
%A Rick Cutfield
%A Jackie Crawford
%A Donald R. Love
%J Case Reports in Medicine
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/647252
%X Sudden unexpected nocturnal death among patients with diabetes occurs approximately ten times more commonly than in the general population. Malignant ventricular arrhythmia due to Brugada syndrome has been postulated as a cause, since a glucose-insulin bolus can unmask the Brugada electrocardiographic signature in genetically predisposed individuals. In this report we present a 16-year-old male with insulin-dependent diabetes who died suddenly at night. His diabetes had been well controlled, without significant hypoglycaemia. At autopsy, he had a full stomach and a glucose level of 7£żmmol/L in vitreous humor, excluding hypoglycaemia. Genetic analysis of autopsy DNA revealed a missense mutation, c.370A>G (p.Ile124Val), in the GPD1L gene. A parent carried the same mutation and has QT prolongation. Mutations in this gene have been linked to Brugada syndrome and sudden infant death. The patient may have died from a ventricular arrhythmia, secondary to occult Brugada syndrome, triggered by a full stomach and insulin. The data suggest that molecular autopsies are warranted to investigate other cases of the diabetic dead-in-bed syndrome. 1. Introduction Sudden unexpected nocturnal death among patients with diabetes is greatly feared and poorly understood, occurring approximately ten times more commonly than in the general population [1]. The Ħ°dead-in-bedĦħ syndrome, by definition, has a negative autopsy and accounts for up to 6% of all deaths in type I diabetics under the age of 40 years [2]. Hypoglycaemia has been put forward as the most likely explanation but has been excluded in some cases [2¨C4]. The possibility that a cardiac ion channelopathy such as long QT syndrome or Brugada syndrome may cause death through a malignant arrhythmia in individuals with diabetes has been considered but never proven [5]. We report the postmortem molecular genetic investigation of a 16-year-old boy with type 1 diabetes who died in his sleep. His blood glucose had been well-controlled; he had a full stomach at autopsy and a glucose level in vitreous humor of 7£żmmol/L. These features argue strongly against hypoglycaemia. Molecular genetic investigation revealed a missense mutation (p.Ile124Val) in the GPD1L gene. GPD1-L catalyses the conversion of sn-glycerol 3-phosphate to glycerone phosphate and binds to the SCN5A ion channel protein; mutations in the GPD1L gene have been linked to Brugada syndrome and to sudden infant death syndrome [6¨C8]. 2. Case History The boy was diagnosed as having type 1 diabetes at the age of 15 years (nine months prior to his death) presenting with
%U http://www.hindawi.com/journals/crim/2014/647252/