Wolcott-Rallison syndrome

Citation metadata

Authors: Cecile Julier and Marc Nicolino
Date: Nov. 4, 2010
From: Orphanet Journal of Rare Diseases(Vol. 5)
Publisher: BioMed Central Ltd.
Document Type: Disease/Disorder overview
Length: 7,611 words
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Authors: C├ęcile Julier (corresponding author) [1,2]; Marc Nicolino (corresponding author) [3,4]

Disease name and synonyms

Wolcott-Rallison syndrome (WRS) was named after Drs Wolcott and Rallison, who first described this syndrome in three affected siblings [1]. It is also known as multiple epiphyseal dysplasia and early-onset diabetes mellitus, according to the main clinical manifestations recognized initially.

Definition and diagnostic criteria

WRS is characterized by insulin-requiring diabetes that generally appears during the neonatal period or in the first six months of life, with a frequently acute presentation of severe diabetic ketoacidosis at disease onset [2, 3, 4]. Two patients with a later onset have been reported, at 14 months [4] and 30 months [2]. Hyperglycemia is initially the only manifestation of the disease, the rest of the biological assessment being normal. Anti-islet cell (ICA), anti-insulin, anti-glutamic acid decarboxylase (GAD) and anti-tyrosine phosphatase (IA2) antibodies are negative. With time, short stature and skeletal dysplasia with radiographic abnormalities progressively develop and are generally diagnosed after diabetes onset, although early signs, including delayed or difficult walking, osteoporosis, deficient mineralization or mild bone abnormalities may be present on close examination and radiography as early as the onset of diabetes. Additional clinical features, which vary between patients, are usually diagnosed after diabetes onset.

Epidemiology

This is a rare disease, with fewer than 60 cases described in the literature [3, 4]. In the large majority of cases, affected individuals are from populations in which consanguineous marriages are frequent, such as the Middle-East, North Africa, Pakistan and Turkey. Despite its recognition as a very rare disease, with very few cases reported in the literature before the first genetic study leading to gene identification, WRS now appears as the most frequent cause of Permanent Neonatal Diabetes Mellitus (PNDM) in consanguineous families ([4] and C. Julier, unpublished data). It is likely that the syndrome was rarely diagnosed before the identification of the responsible gene, and may still be underdiagnosed, as patients may die before expressing the minimum clinical features of neonatal/early-onset diabetes and epiphyseal dysplasia or because the association may not be recognized in younger patients.

Clinical characteristics

The two main clinical features are well described in the first publication of Wolcott and Rallison [1], and are represented by neonatal/early-onset diabetes and multiple epiphyseal dysplasia. Hepatic dysfunction, manifesting in the form of elevated hepatic enzymes, liver enlargement and recurrent acute liver failure, is the third most frequently observed manifestation, and now appears as a characteristic feature of this syndrome. This review is based on the clinical characteristics of patients in our own experience and on the description of cases reported in the literature, as well as two recent compilations of large series of WRS patients: a description of new cases and literature review of 38 patients from 23 families [3] and a recent study of 29 WRS patients from 25 families [4].

Diabetes

In the vast majority of cases the onset is observed during the first months of life (extreme ages at onset between 1 day and 30 months). In all...

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Source Citation

Source Citation
Julier, Cecile, and Marc Nicolino. "Wolcott-Rallison syndrome." Orphanet Journal of Rare Diseases, vol. 5, 2010, p. 29. Accessed 6 Aug. 2020.
  

Gale Document Number: GALE|A242777708