Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients.

Alice Clerc,Christine Poitou,Christine Poitou,Christine Poitou,Christine Poitou,Gwenaëlle Diene,Maithé Tauber,Christine Merrien,Christine Merrien,Graziella Pinto,Graziella Pinto,Héléna Mosbah,Héléna Mosbah,Virginie Laurier,Virginie Laurier,Muriel Coupaye,Muriel Coupaye,Fabien Mourre,Fabien Mourre

doi:10.3390/jcm10225310

Abstract

Type 2 diabetes mellitus (T2DM) affects 20% of patients with Prader-Willi syndrome (PWS), with many cases diagnosed during the transition period. Our aim was to describe the natural history of T2DM in patients with PWS before the age of 25 years and to develop screening and preventive strategies. Thirty-nine patients followed in the French PWS Reference Center were included (median age 25.6 years [23.7; 31.7]). Twenty-one had been treated with growth hormone (GH), fifteen had not, and three had an unknown status. The median age at T2DM diagnosis was 16.8 years (11–24) and the median BMI was 39 kg/m2 [34.6; 45], with 34/35 patients living with obesity. The patients displayed frequent psychiatric (48.3% hospitalization,) and metabolic (56.4% hypertriglyceridemia,) comorbidities and a parental history of T2DM (35.7%) or overweight (53.6%) compared to the PWS general population. There was no difference in BMI and metabolic complications between the GH-treated and non-GH-treated groups at T2DM diagnosis. Patients with PWS who develop early T2DM have severe obesity, a high frequency of psychiatric and metabolic disorders, and a family history of T2DM and overweight. These results underline the need for early identification of patients at risk, prevention of obesity, and repeated blood glucose monitoring during the transition period.

Highlights

Prader-Willi syndrome (PWS) is a rare genetic disorder with an incidence of 1 in21,000 births [1]
The diagnosis of PWS was made at a median age of 29 months [3.75; 157] and 59% of patients had a deletion
We found that 33.3% of our patients were born Small for gestational age (SGA), which is comparable to the 30% observed in the general PWS population [8]

Summary

Introduction

Prader-Willi syndrome (PWS) is a rare genetic disorder with an incidence of 1 in. It is usually caused by the loss of paternally inherited imprinted genes at 15q11.2-q13. In about 60–65% of cases, the cause is a paternal 15q11-q13 deletion (DEL). In the remaining cases, the cause is a maternal uniparental disomy of chromosome. Infants display severe hypotonia and sucking-swallowing deficits that interfere with feeding and decrease weight gain. They develop excessive weight gain, hyperphagia, and obsession towards food that leads to severe early obesity in the absence of strict control of food access in a firm and caring environment [3].

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