Wolfram syndrome

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Description from OMIM

Wolfram syndrome-1 is a rare and severe autosomal recessive neurodegenerative disease characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and deafness (DIDMOAD). Additional clinical features may include renal abnormalities, ataxia, dementia or mental retardation, and diverse psychiatric illnesses. The minimal diagnostic criteria for Wolfram syndrome are optic atrophy and diabetes mellitus of juvenile onset. Hearing impairment in Wolfram syndrome is typically progressive and mainly affects the higher frequencies, but a small fraction of affected individuals have congenital deafness (summary by Rendtorff et al., 2011). Autosomal dominant mutations in the WFS1 gene have been found to cause low-frequency nonsyndromic deafness (600965) as well as a Wolfram syndrome-like phenotype (614296) in which affected individuals have hearing impairment with diabetes mellitus and/or optic atrophy. Genetic Heterogeneity of Wolfram Syndrome Wolfram syndrome-2 (WFS2; 604928) is caused by mutation in the CISD2 gene (611507) on chromosome 4q22-q24. See 598500 for a possible mitochondrial form of Wolfram syndrome.



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List of symptoms



Symptom/sign Organ system Percent affected Pubmed id Added on(yyyy-mm-dd) Edit/add reference
Diabetes mellitus type 1 endocrine 100 % 20972738 2011-10-19
Optic atrophy nervous 97 % 20972738 2011-10-01
Hearing loss nervous 59 % 20972738 2011-10-01
Diabetes insipidus nervous 53 % 20972738 2011-10-01
Ataxia nervous 33 % 7490992 2011-10-01
Gastrointestinal dysmotility digestive 24 % 7490992 2011-10-01
Areflexia nervous 20 % 7490992 2011-10-01
Myoclonus nervous 20 % 7490992 2011-10-01
Psychiatric symptom nervous 18 % 20972738 2011-10-01
Nystagmus nervous 16 % 7490992 2011-10-01
Apnea nervous 11 % 7490992 2011-10-01
Dysarthria nervous 11 % 7490992 2011-10-01
Cataract nervous 7 % 20972738 2011-10-01



List of references:


WS1 gene mutation analysis of Wolfram syndrome in a Chinese patient and a systematic review of literatures.
Guang Yu, Man-li Yu, Jia-feng Wang, Cong-rong Gao, Zhong-jin Chen,

Wolfram syndrome is a rare hereditary disease characterized by diabetes mellitus and optic atrophy. The outcome of this disease is always poor. WFS1 gene mutation is the main cause of this disease. A patient with diabetes mellitus, diabetes insipidus, renal tract disorder, psychiatric abnormality, and cataract was diagnosed with Wolfram syndrome. Mutations in open reading frame (ORF) of WFS1 gene was analyzed by sequencing. Mutations in WFS1 gene was also summarized by a systematic review in Pubmed and Chinese biological and medical database. Sequencing of WFS1 gene in this patient showed a new mutation, 1962G>A, and two other non-sense mutations, 2433A>G and 2565G>A. Systematic review included 219 patients in total and identified 172 WFS1 gene mutations, most of which were located in Exon 8. These mutations in WFS1 gene might be useful in prenatal diagnosis of Wolfram syndrome.

Endocrine - Oct 2010



Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome.
T G Barrett, S E Bundey, A F Macleod,

Wolfram syndrome is the association of diabetes mellitus and optic atrophy, and is sometimes called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Incomplete characterisation of this autosomal recessive syndrome has relied on case-reports, and there is confusion with mitochondrial genome disorders. We therefore undertook a UK nationwide cross-sectional case-finding study to describe the natural history, complications, prevalence, and inheritance of the syndrome. We identified 45 patients with Wolfram syndrome--a prevalence of one per 770,000. Non-autoimmune, insulin-deficient diabetes mellitus presented at a median age of 6 years, followed by optic atrophy (11 years). Cranial diabetes insipidus occurred in 33 patients (73%) with sensorineural deafness (28, 62%) in the second decade; renal-tract abnormalities (26, 58%) presented in the third decade followed by neurological complications (cerebellar ataxia, myoclonus [28, 62%]) in the fourth decade. Other abnormalities included gastrointestinal dysmotility in 11 (24%), and primary gonadal atrophy in seven of ten males investigated. Median age at death (commonly central respiratory failure with brain-stem atrophy) was 30 years (range 25-49). The natural history of Wolfram syndrome suggests that most patients will eventually develop most complications of this progressive, neurodegenerative disorder. Family studies indicate autosomal recessive inheritance with a carrier frequency of one in 354, an absence of a maternal history of diabetes or deafness, and an absence of the mitochondrial tRNA Leu (3243) mutation. Juvenile-onset diabetes mellitus and optic atrophy are the best available diagnostic criteria for Wolfram syndrome, the differential diagnosis of which includes other causes of neurodegeneration.

Lancet (London, England) - Dec 1995