Morbidity and mortality in the Wolfram syndrome.

OBJECTIVE: To determine the major causes of morbidity and mortality in the autosomal recessive Wolfram syndrome, which is defined by diabetes and bilateral progressive optic atrophy with onset in childhood or adolescence. RESEARCH DESIGN AND METHODS: We abstracted and reviewed the medical records of 68 confirmed cases of Wolfram syndrome identified through a nationwide survey of endocrinologists, ophthalmologists, institutes, and homes for the blind. We also reviewed all available autopsy records. RESULTS: The most common causes of morbidity and mortality were the neurological manifestations of this syndrome and the complications of urinary tract atony. There was a lower frequency of diabetic ketoacidosis, no histologically proven diabetic glomerulosclerosis, and less severe, more slowly progressive, diabetic retinopathy than in classic type I diabetic patients. Mortality in Wolfram syndrome is much higher than in type I diabetes; 60% of Wolfram syndrome patients die by age 35. Recognition of these clinical differences from classic type I diabetes is important for the proper management of Wolfram syndrome patients. CONCLUSIONS: Identification of Wolfram syndrome patients among all diabetic patients presenting in childhood or adolescence is important because the management of patients with this syndrome is different from that of patients with classic type I diabetes.

Psychosocial predictors of acute complications of diabetes in youth.

In this paper we determine whether individual and family psychosocial functioning predicts the risk for recurrent acute diabetic complications. An onset-cohort of 61 children and adolescents with Type 1 diabetes received conventional diabetes care. Episodes of ketoacidosis and of severe hypoglycemia were recorded for 8 years, and glycaemic control was measured by glycohaemoglobin. Measures of psychosocial functioning of the patient and parents were obtained during the first year. Over 8 years, 28% of subjects had at least one episode of ketoacidosis, and 21% had at least one episode of hypoglycaemia. The odds of observing recurrent hypoglycaemia versus recurrent ketoacidosis was 14 times greater in boys than in girls (Fisher's exact test p < 0.05). Girls with recurrent ketoacidosis had more behaviour problems and lower social competence, they reported higher levels of family conflict, and their parents reported lower levels of family cohesion, expressiveness and organization in year one. These relationships were independent of any association with poor glycaemic control. Recurrent hypoglycaemia in boys was generally unrelated to individual and family functioning or glycohaemoglobin. Despite our small sample size, our findings are suggestive of relationships that may lead to early identification of patients who are prone to recurrent ketoacidosis, and to the development of early intervention strategies.

Family environment and glycemic control: a four-year prospective study of children and adolescents with insulin-dependent diabetes mellitus.

An onset cohort of children and adolescents with insulin-dependent diabetes mellitus (IDDM) and their parents were studied. Aspects of family environment were evaluated at study inception, and their influence on the initial level of, and change in, glycemic control over 4 years was examined. Family measures of expressiveness, cohesiveness, and conflict were linked to differences in the longitudinal pattern of glycemic control. In particular, the encouragement to act openly and express feelings directly (expressiveness) seemed to ameliorate deterioration of glycemic control over time in both boys and girls. Boys were especially sensitive to variations in family cohesiveness and conflict; those from more cohesive and less conflicted families showed less deterioration in glycemic control. This study demonstrated the important influence of family psychosocial factors present at diabetes onset on glycemic control in children and adolescents over the first 4 years of IDDM.