Diabetes management in Wolcott-Rallison syndrome: analysis from the German/Austrian DPV database

Abstract

Background: Wolcott-Rallison syndrome (WRS) is characterized by permanent early-onset diabetes, skeletal dysplasia and several additional features, e.g. recurrent liver failure. This is the first multicentre approach that focuses on diabetes management in WRS. We searched the German/Austrian Diabetes-Patienten-Verlaufsdokumentation (DPV) registry and studied anthropometric characteristics, diabetes treatment, glycaemic control and occurrence of severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) in 11 patients with WRS. Furthermore, all local treatment centres were personally contacted to retrieve additional information on genetic characteristics, migration background and rate of consanguinity. Results: Data were analysed at diabetes onset and after a median follow-up period of 3 (1.5-9.0) years (time from diagnosis to latest follow-up). Median age at diabetes onset was 0.2 (0.1-0.3) years, while onset was delayed in one patient (aged 16 months). Seventy percent of patients manifested with DKA. At follow-up, 90% of patients were on insulin pump therapy requiring 0.7 [0.5-1.0] IU of insulin/kg/d. More than two third of patients had HbA1c level ≥ 8%, 40% experienced at least one episode of SH in the course of the disease. Three patients died at 0.6, 5 and 9 years of age, respectively. To the best of our knowledge three patients carried novel mutations in EIF2AK3. Conclusion: Insulin requirements of individuals with WRS registered in DPV appear to be comparable to those of preschool children with well-controlled type 1 diabetes, while glycaemic control tends to be worse and episodes of SH tend to be more common. The majority of individuals with WRS in the DPV registry does not reach glycaemic target for HbA1c as defined for preschool children (< 7.5%). International multicentre studies are required to further improve our knowledge on the care of children with WRS.

Identification of Two Novel Compound Heterozygous EIF2AK3 Mutations Underlying Wolcott–Rallison Syndrome in a Chinese Family

“…Because the variable of the clinical phenotype and the difference in gene penetrance except PNDM of the patients with WRS, the diagnosis of WRS was difficult. As the most common gene causing PNDM are ABCC8 gene and KCNJ11 gene ( 9 ), the analysis of EIF2AK3 gene is always ignored in molecular diagnosis. It seems that WRS should be considered in the molecular diagnose of PNDM even when the incidence of WRS is very low.…”

“…Long-term regular insulin therapy has been demonstrated to improve the survival rates of WRS patients. Organ transplantation is a treatment for WRS; so far, three cases with organ transplantation have been reported (7)(8)(9), and these three patients were fully physically and socially rehabilitated.…”

ISPAD Clinical Practice Consensus Guidelines 2022: Insulin treatment in children and adolescents with diabetes

“…Rapid‐acting insulin can be diluted to 1/10 (U10) or U50 with sterile NPH diluent and stored for 1 month 67 for use in pumps for infants or very young children. Insulin diluted in a 1/5 ratio (U20 insulin; 20 units/ml) has been used successfully during automated insulin treatment in young children (3–6 years old) with T1D 68–72 . Dosing errors with unconventional insulin concentrations can be serious.…”

“…for infants or very young children. Insulin diluted in a 1/5 ratio (U20 insulin; 20 units/ml) has been used successfully during automated insulin treatment in young children (3-6 years old) with T1D [68][69][70][71][72]. Dosing errors with unconventional insulin concentrations can be serious.…”

Genetic spectrum of neonatal diabetes

“…If mutated, it causes endoplasmic stress and initiates apoptosis in many tissues including β-cells. About 20 different mutations have so far been reported, children present with ketoacidosis and insulin therapy is mandatory [24,91,92].…”