Wolfram Syndrome

Diabetes mellitus and insipidus with optic nerve atrophy, mental retardation and deafness.

Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness; DIDMOAD.

Genetic syndrome that was first described by D.J. Wolfram in 1938.

Unknown; males and females are equally affected.

Autosomal recessive.

Caused by a mutation in the gene encoding wolframin (WFS1) on chromosome 4p16.1. Another locus for the disorder has been mapped to 4q (WFS2). Marked atrophy and degeneration is seen in the pons, the medullary reticular activating system, substantia nigra, superior and inferior olives, and the cerebellum. Microscopically, neuronal loss and axonal destruction, often accompanied by gliosis, is apparent, together with scattered areas of demyelination in the cerebrum and cerebellum, without inflammatory change.

A combination of juvenile-onset diabetes mellitus and optic nerve atrophy plus one or more of the following: anosmia, brainstem signs (gaze palsies, nystagmus, dysarthria, dysphagia, primary respiratory failure), deafness, seizures or myoclonus, ataxia, axial rigidity, neuropsychiatric or cognitive abnormalities, neurogenic incontinence or dilated urinary tract, hyporeflexia or areflexia, extensor plantar responses, diabetes insipidus, and family history.

Diabetes mellitus, diabetes insipidus, optic nerve atrophy, sensorineural hearing loss, autonomic dysfunction, cardiomyopathy, mental retardation, seizures, nystagmus, hydronephrosis, megaloblastic anemia, sideroblastic anemia, neutropenia, thrombocytopenia.

A complete evaluation of the cardiac function (clinical, ECG, echocardiography) must be obtained. Evaluate neurological function (clinical, EEG, CT scan), hematology, and biochemistry.

Perioperative fluid regimen should be adapted to diabetes insipidus. The use of regional anesthetic technique, especially neuraxial approach, must consider the potential for autonomic dysfunction and hemodynamic instability. A close control of preand intraoperative glycemia must be done.

Consider interaction between anesthetic drugs and antiepileptic treatment. Avoid enflurane. Consider renal function and whether beneficial to use aminoglycosides.

Wolfram Syndrome, Mitochondrial Form with Vasopressin Deficiency: Low erythrocyte thiamine pyrophosphate. Low thiamine pyrophosphokinase activity. Heteroplasmic mtDNA deletion. Mild hyperlactatemia.