Liver disease and other comorbidities in Wolcott-Rallison syndrome: different
phenotype and variable associations in a large cohort
#MMPMID25659842
Habeb AM
; Deeb A
; Johnson M
; Abdullah M
; Abdulrasoul M
; Al-Awneh H
; Al-Maghamsi MS
; Al-Murshedi F
; Al-Saif R
; Al-Sinani S
; Ramadan D
; Tfayli H
; Flanagan SE
; Ellard S
Horm Res Paediatr
2015[]; 83
(3
): 190-7
PMID25659842
show ga
BACKGROUND: Wolcott-Rallison syndrome (WRS) is caused by recessive EIF2AK3
mutations and characterized by early-onset diabetes and skeletal dysplasia.
Hepatic dysfunction has been reported in 60% of patients. AIMS: To describe a
cohort of WRS patients and discuss the pattern and management of their liver
disease. METHODS: Detailed phenotyping and direct sequencing of EIF2AK3 gene were
conducted in all patients. RESULTS: Twenty-eight genetically confirmed patients
(67% male; mean age 4.6 years) were identified. 17 different EIF2AK3 mutations
were detected, of which 2 were novel. The p.S991N mutation was associated with
prolonged survival and p.I650T with delayed onset. All patients presented before
25 months with diabetes with variation in the frequency and severity of 10 other
features. Liver disease, first manifested as non-autoimmune hepatitis, was the
commonest extra-pancreatic feature identified in 85.7% (24/28). 22/24 had at
least one episode of acute hepatic failure which was the cause of death in all
deceased patients (13/28). One child was treated by liver transplantation and had
no liver disease and better diabetes control for the following 6 years.
CONCLUSIONS: Liver disease in WRS is more frequent than previously described and
carries high mortality. The first experience with liver transplantation in WRS is
encouraging.
|*Diabetes Mellitus, Type 1/genetics/mortality/surgery
[MESH]
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