(Syndrome DIDMOAD [Diabetes Insipidus, Diabetes Mellitus, Ociwp Atrophy, Deafness])

Very rare, autosomal recessive transmission. Association of a juvenile insulin-dependent diabetes and an optic atrophy. Once considered as a mitochondrial disease, it is actually known as a functional abnormality of the endoplasmic reticulum one function of which is the deployment of secreted  proteins (such as insulin) and receptors located at the cell surface. The accumulation of malformed proteins in the endoplasmic reticulum  causes a 'stress' on this structure which can be decreased by the activation of a process that restores its homeostasis. This response also maintains the function and survival of pancreatic β cells. In this syndrome, the endoplasmic stress response is exaggerated and causes early apoptosis of pancreatic β cells.

There are two types:

-        Wolfram type 1 syndrome [MIM 606 201] caused by the loss of function of the WFS1 gene (on 4p16.1), which codes for the wolframin, a transmembrane protein located in the endoplasmic reticulum; difficult diagnosis as all the signs do not develop at the same time: juvenile diabetes (start from 3 weeks to 16 years), optic atrophy (average age 11 years) with decrease of visual acuity and loss of color vision); central origin diabetes insipidus (average age 14 years) responding to  nasal or oral desmopressin; progressive hearing loss (average age 16 years) and neurological abnormalities that appear around 30 years: truncal ataxia, loss of the vomiting reflex, epilepsy, central apnea that are the usual cause of death (average age: 30 years). Sometimes: gastroparesis (29%), hypogonadism, cardiac abnormalities, neurogenic urinary bladder with dilation of the urinary tract. Partial hypopituitarism of hypothalamic origin has been described in a group of patients.

-        Wolfram type 2 syndrome [MIM 604 928] caused by the mutation of the CISD2 gene (on 4q22), which would cause a mitochondrial impairment linked to the anomaly of the endoplasmic reticulum: juvenile diabetes with deafness, optic atrophy, dilation of the urinary tract with renal function impairment, hypogonadism, tendency to peptic ulcers but absence of diabetes insipidus. Tendency to bleeding following a deficit of platelet aggregation (in certain ethnic groups)

Anesthetic implications:

-        diabetes mellitus

-        diabetes insipidus; check the pituitary function: a supplement of hydrocortisone may be necessary in case of stress.

-        deafness and blindness;

-        monitor renal function (hyper or hypoactive urinary bladder, megabladder)

-        risk of apnea and aspiration

-        if type 2: seek specialized advice for the hemostasis evaluation

References : 

-         Rigoli L, Di Bella C. 
Wolfram syndrome 1 and Wolfram syndrome 2. 
Curr Opin Pediatr 2012; 24: 512-7.

-        Wragg R, Dias RP, Barrett T, McCarthy L.
Bladder dysfunction in Wolfram syndrome is highly prevalent and progresses to megacystis.
J Pediatr Surg 2018 ; 53 : 321-5

Updated: March 2018