Diabetes mellitus and insipidus with optic nerve atrophy,
mental retardation and deafness.
Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and
Genetic syndrome that was first described by D.J. Wolfram
Unknown; males and females are equally affected.
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
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
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
Ajlouni K, Jarrah N, El-Khateeb M, et al: Wolfram syndrome:
Identification of a phenotypic and genotypic variant from Jordan. Am J Med Genet
El-Shanti H, Lidral AC, Jarrah N, et al: Homozygosity mapping identifies an
additional locus for Wolfram syndrome on chromosome 4q. Am J Hum Genet
Minton JA, Rainbow LA, Ricketts C, et al: Wolfram syndrome. Rev Endocr Metab Disord