Wolcott-Rallison syndrome

(MIM 226980)

(Precocious diabetes and multiple epiphyseal dysplasia)

Rare. Autosomal recessive (frequent inbreeding) transmission of mutations of the EIF2AK3 gene which codes for the PERK protein which plays a major role in the endoplasmic reticulum to eliminate malformed proteins, including at the level of the pancreatic β cells and the bone tissue.

Association of:

-        diabetes mellitus starting in the neonatal period or in the first 6 months of life; it is associated with hypoplasia of the pancreas but there are no autoantibodies.

-        multiple epiphyseal dysplasia associated with short stature: important osteopenia (frequent fractures), epiphyseal dysplasia of long bones, vertebrae (platyspondyly, kyphosis, exaggerated lumbar lordosis) and pelvic bones (coxa vara, femoral head); sometimes, instability of the cervical spine (hypoplasia of the atlas).

-        liver disease: recurrent episodes of cytolysis with hepatomegaly with or without cholestasis, triggered by intercurrent infections; histology: progressive fibrosis with steatosis and intrahepatic cholestasis.

Sometimes: neutropenia, exocrine pancreatic insufficiency, hypothyroidism, kidney failure. Highly variable evolution but frequent death in childhood from acute hepatic or multisystem failure. 


Anesthetic implications: 

Check blood glucose, liver and kidney function. Bone fragility. Caution during mobilization of the neck. Poorly documented notion of increased sensitivity to anesthetic agents. Avoid hepatotoxic drugs.


References:

-         Julier C, Nicolino M. 
       Wolcott-Rallison syndrome. 
       Orphanet Journal of Rare Diseases 2010 ; 5 : 29

-         Senéée V, Vattem KM, Delépine M et al. 
Wolcott-Rallison syndrome. 
Diabetes ; 2004 : 53 : 1876-83.

-         Engelmann G, Meyburg J, Shahbek N, Al-Ali M et al. 
Recurrent acute liver failure and mitochondriopathy in a case of Wolcott-Rallison syndrome. 
J Inherit Metab Dis 2008; 31: 540-6.

-        Uroic AS, Kotori VM, Putarek NR, Kusec V, Dumic M. 
Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome. 
Eur J Pediatr 2014; 173: 529-31.

-         Romera ACR, Hervias M, Lopez-Gill MT, Tranche I. 
Anaesthesia and orphan disease: a child with Wolcott-Rallison syndrome. 
Eur J Anaesthesiol 2015 ; 32 : 217-8


Updated: August 2018