Diabetes mellitus, diabetes insipidus, optic atrophy and deafness (DIDMOAD syndrome)

Two patients with diabetes mellitus (DM), diabetes insipidus (DI), optic atrophy (OA), deafness (D) and dilatation of the urinary tract-the so-called DIDMOAD syndrome are presented. In one of the patients, the presenting components were DI and OA. In the second case, DM was the first manifestation to be diagnosed, and in this patient the course of the syndrome was complicated by associated epileptical activity disorders, and later septicemia. The admission of these patients led us to review the literature describing this syndrome.     

Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD syndrome). A clinical study in two Sudanese families

Four Sudanese children with DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) are reported. They were two boys (aged 15 and 16 years) in one family and a boy and a girl (aged 16 and 6 years, respectively) in another family. Diabetes mellitus was first to appear (at 3-8 years) followed by deafness and visual failure; and the disease ended fatally in one patient (aged 20 years). In the other three, diabetes insipidus was confirmed using water deprivation test for 8 hours. The maximum urine osmolality ranged between 131-523 mOsm/kg, whereas the corresponding plasma osmolality ranged between 315-332 mOsm/kg. Slight further improvement in urine concentration was observed in 2 of the patients following the use of desmopressin (DDAVP, 20 micrograms intranasally). Intravenous pyelography, voiding cystourethrography and ultrasound revealed severe bilateral hydronephrosis, dilated ureters and distended bladder without vesicoureteral reflux in the three patients. With the high rate of consanguinity prevalent in North Africa and the Middle East, we recommend examining children who present with diabetes mellitus in this region for features of DIDMOAD syndrome.     

Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. 3 cases of 'DIDMOAD' syndrome

Three children with diabetes insipidus, diabetes mellitus, optic atrophy, and high-tone deafness were shown to lack vasopressin, indicative of degeneration of the cells of the hypothalamic supraoptic nuclei. The syndrome being due to a single gene defect, inherited as an autosomal recessive, is therefore likely to be the result of an inborn error of metabolism with variable periods of latency in those affected.     

Diabetes insipidus, diabetes mellitus, optic atrophy and labyrinthine deafness: the DIDMOAD-syndrome (author's transl)

The DIDMOAD syndrome is a combination of diabetes mellitus, diabetes insipidus, optic atrophy and labyrinthine deafness. The inheritance is autosomalrecessive. Diagnostic and therapeutic possibilities are discussed on the basis of a further case of this pathogenetically not yet clarified disease pattern. Early detection of this syndrome in juvenile diabetics is important for long-term prognosis and genetic family advice.     

Diabetes insipidus, diabetes mellitus, optic nerve atrophy, and deafness--an autosomal recessive syndrome (didmoad-syndrome) (author's transl)

By reporting a further case attention is drawn to the autosomal recessive inherited DIDMOAD-syndrome. While diabetes mellitus and optic atrophy are easy to recognize, one often has specifically to look for deafness, diabetes insipidus and the frequently associated dilatation of the urinary tract. Awareness of this condition is important for genetic counselling and vocational guidance, and allows to avoid invasive neuroradiological investigations.     

The subtle signs of Wolfram (DIDMOAD) syndrome: not all juvenile diabetes is type 1 diabetes

Wolfram syndrome (also known as DIDMOAD = diabetes insipidus, diabetes mellitus, optic atrophy, deafness) is an autosomal recessive disorder characterized by the association of childhood non-immune insulin-dependent diabetes mellitus (DM) with progressive bilateral optic atrophy. Additional symptoms including signs of severe neurodegeneration and psychiatric illness are likely to evolve over time resulting in premature death. We report on two siblings of Turkish origin from our diabetes clinic who were diagnosed with Wolfram syndrome after 6 years and 2 years duration of DM, respectively. Subtle symptoms such as attitude changes, growing reading difficulties in the history of children or adolescents with antibody negative and ketone negative DM should alert the treating physician and lead to re-evaluation of the diagnosis, keeping in mind that not all juvenile DM is type 1 DM.     

Wolfram/DIDMOAD syndrome, a heterogenic and molecularly complex neurodegenerative disease

Wolfram syndrome (WS, OMIM 22233), is a rare, autosomal recessive, and neurodegenerative disease. The syndrome is also known as DIDMOAD, the acronym for diabetes insipidus diabetes mellitus, optic atrophy and deafness, which summarizes the main clinical features, among many others, in WS patients. The gene associated with the syndrome, called WFS1, is located in the 4p16.1 region. The WFS1 gene encodes for a transmembrane protein located in the endoplasmic reticulum. Although the function of the WFS1 protein remains unknown, it is thought to be related with intracellular calcium homeostasis. The pattern of presentation of WS suggested the existence of mitochondrial impairment. Mitochondrial DNA rearrangements were detected in some patients, thus confirming that hypothesis. Recently, a particular WS phenotype has been described linked with the long arm of chromosome 4. This work aims to summarize the current knowledge about this disease that causes a heterogeneous phenotype and has a complex molecular aetiology.     

Wolfram (DIDMOAD) syndrome: report of two patients

We report a girl with Wolfram syndrome who presented with juvenile-onset diabetes mellitus when she was 4 3/12 years old. Optic atrophy and high frequency sensorineural hearing loss were found at 7 and 9 5/12 years of age, respectively. Her younger brother also developed Wolfram syndrome when he was 3 2/12 years old. Wolfram syndrome is also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). This syndrome is transmitted as an autosomal recessive trait and is a progressive neurodegenerative disorder. It should be considered in a diabetic patient with unexplained optic atrophy, hearing loss, or polyuria and polydipsia in the presence of adequate blood glucose control. Visual acuity should be checked annually in patients with juvenile-onset diabetes mellitus. Optic atrophy should be considered if visual acuity is impaired.     

Empty sella syndrome, panhypopituitarism, and diabetes insipidus

We present an 18-month-old girl with short stature, obesity, panhypopituitarism, diabetes insipidus, and visual defects. Postmortem examination revealed brain atrophy due to a diffuse encephalopathy, numerous calcified neurons in cerebral cortex, deep telencephalic and diencephalic nuclei, diffuse neuronal necrosis in hypothalamic nuclei, moderate atrophy of optic nerves, very thin hypophyseal stalk, and empty sella with the hypophysis compressed to the dorsal aspect of the concavity. Our hypothesis is that the presence of an empty sella in a child with hypophyseal-hypothalamic abnormalities should alert physicians to the existence of hypothalamic lesions secondary to a perinatal insult. We discuss the possible pathogenesis of these findings as well as lines of evidence available in the literature.     

The primary empty-sella syndrome and diabetes insipidus in a child

The empty-sella syndrome is uncommon in pediatric patients. Hypothalamic-pituitary dysfunction is common in these patients but involvement of the posterior pituitary gland is very rare. We report a seven-year-old girl with empty-sella syndrome who first developed arginine-vasopressin deficient diabetes insipidus and then anterior pituitary gland deficiency. The empty-sella syndrome should be included among the causes of arginine-vasopressin deficient diabetes insipidus in pediatric patients.     

Wolfram (DIDMOAD) syndrome: a multidisciplinary clinical study in nine Turkish patients and review of the literature

Aim: To study Wolfram syndrome (WFS) with multidisciplinary consultations and compare the results with the literature. Methods: Nine patients fulfilled the ascertainment criteria of WFS (insulin-dependent diabetes mellitus and optic atrophy). All patients were evaluated by the departments of paediatrics, ophthalmology, audiology, urology and medical biology. Results: The earliest manifestation of WFS was insulin-dependent diabetes mellitus (at a median age of 6.9 y), followed by optic atrophy (8.9 y), diabetes insipidus (10.2 y) and deafness (10.5 y). Short stature was found in five cases, delayed puberty in two cases and hypergonadotropic hypogonadism in one case. Audiography disclosed hearing loss at high frequency in all patients (100%), but only five patients had clinical subjective hearing problems. Intravenous pyelography revealed hydroureteronephrosis in eight patients. Urodynamics revealed a normal bladder in only one patient. Three patients had a low-capacity, low-compliance bladder, detrusor external sphincteric dyssynergia and emptying problem, while five had an atonic bladder. Ocular findings were optic atrophy, low visual acuity and colour vision defects. Visual field tests revealed concentric and/or peripheral diminution in five patients. Visual evoked potentials were abnormal (reduced amplitude to both flash and pattern stimulation) in seven patients. Cranial magnetic resonance imaging showed mild or moderate atrophy of the optic nerves, chiasm, cerebellum, basal ganglia and brainstem in six patients; there was a partially empty sella in one case. There was no evidence of mitochondrial tRNA Leu (UUR) A to G (nucleotide 3243) mutation. Conclusion: Wolfram syndrome should be evaluated in a multidisciplinary manner. Some specific and dynamic tests are necessary to make a more precise estimate of the prevalence and median age of the components of WFS. Short stature is a common feature in WFS. Hypogonadism may be hypogonadotropic or hypergonadotropic. Bladder dysfunction does not always present as a large atonic bladder in WFS. A low-capacity, high-pressure bladder with sphincteric dyssynergia is also common.