Multicystic dysplastic kidney: a new association of Wolcott–Rallison syndrome

Abstract

Wolcott–Rallison syndrome (WRS) is a rare autosomal recessive disorder due to mutations in the EIF2AK3 gene. It is characterized by permanent neonatal diabetes mellitus, skeletal dysplasia, liver impairment, neutropenia and renal dysfunction. Liver is the most commonly affected organ and liver failure is the commonest cause of death in this syndrome. The EIF2AK3 gene encodes a transmembrane protein PERK, which is important for the cellular response to endoplasmic reticulum (ER) stress. The absence of PERK activity reduces the ER’s abilities to deal with stress, leading to cell death by apoptosis. On acquiring febrile illness, affected patients suffer from liver injury, which may progress into liver failure and death. Renal involvement is less common and is mainly in the form of functional renal impairment at the advanced stage of the disease. Structural renal anomalies have not been reported in WRS. We report a 6-month-old girl who presented with neonatal diabetes on day 1 of life. Her genetic testing confirmed WRS due to missense mutation in the EIF2AK3 gene (c.2867G > A, p.Gly956Glu). Parents are first-degree cousins and both are heterozygous carriers to the mutation. 2 paternal uncles had the same mutation and died of liver disease at 1 and 14 years of age. Neither had a renal disease. She presented with hematuria during a febrile illness at the age of 5 months. Ultrasound scan showed right ectopic multicystic dysplastic kidney (MCDK). To the best of our knowledge, this is the first patient with WRS who is reported to have an MCDK disease.Learning points:Neonatal diabetes should be considered in babies presenting with early hyperglycemia particularly if there is a family history.Genetic diagnosis in neonatal diabetes enables disease confirmation, genetic counseling and anticipation of potential complications during concomitant situations such as acute illness, trauma or major surgery.There is lack of phenotype–genotype correlation in Wolcott–Rallison syndrome.Structural kidney abnormality, in our case MCDK, can be seen in WRS.

Natural history of Wolcott‐Rallison syndrome: A systematic review and follow‐up study

“…The study cohort comprises 159 individuals identified through a systematic literature search from 62 studies 4,5,7,17–75 (Figure 1) and an additional 30 individuals who were collected via contacting physicians and study authors (Supplemental Table S1). Additional follow‐up data were acquired on 11 individuals already reported 7,24–26,28,45 via direct contact with the original study authors.…”

Kidney biopsy findings in children with diabetes mellitus

“…In this syndrome, the most usual way in which the kidneys are affected is by episodes of acute, reversible kidney dysfunction when there is liver dysfunction [13]. Permanent structural changes in the kidney have only rarely been reported [14,29], and in particular, diabetic glomerulopathy seems not to have been reported.…”