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Washington University Experience | MYELIN (NON-IMMUNE MEDIATED) | Vanishing White Matter Dz | 1A0 Case 1 History
Case 1 History (AANP DSS 2008, Case 1, Thanks to Dr. Carrie Mohila) ---- The patient is 36 year old woman whose neurological history began at age 17 when a head CT was performed for post traumatic headaches following a motor vehicle accident and revealed bilateral diffuse white matter disease of unknown etiology. Over the following 1-2 years she had several episodes which were characterized by headaches, blurred vision, hemianopia, expressive aphasias, seizure-like activity, and extremity numbness and weakness thought consistent with complex migraines. The “episodes” continued to increase in frequency over the ensuing years and included additional symptoms such as bizarre behavior, wrist drop, facial drooping, and clonus and increased in duration (for 12-48 hours). At age 27, following a fall she had an acute neurologic event requiring hospitalization which left her lethargic and unable to carry out her activities of daily living. MRI revealed diffuse white matter abnormalities in the centrum semiovale and periventricular region with marked ventricular dilation. Extensive metabolic workup was negative. She received a diagnosis of CADASIL, despite negative skin, nerve, and muscle biopsies. In 1999 at age 29, she experienced sudden unresponsiveness and status epilepticus requiring hospitalization which left her in a persistent vegetative state with facial grimacing, crying, moaning, occasional seizures, hand twitching, myoclonic jerks, and no purposeful movement. She was discharged to a skilled nursing facility. Over the ensuing years, she had a stepwise progressive deterioration. She died at the age of 36. Pertinent negative laboratory results include: absence of NOTCH3 mutations, with sequencing of exons 3, 4, 11, 18, and 19 plus 28 other exons, and absence of mutations in the mitochondrial genome. Necropsy findings: General autopsy revealed the immediate cause of death to be bilateral acute pneumonia. The brain weighed 890 grams. There was dramatic cystic degeneration of the corona radiata bilaterally with relative sparing of the basal ganglia. The cerebellum and brainstem were unremarkable Genetic studies revealed that this patient was compound heterozygous for two mutations in the gene eiF2B5: 338G>A mutation leading to the substitution of arginine for histidine in eiF2B at position 113 (R113H), and 1015C>T mutation leading to the substitution of arginine for tryptophan in eIF2B at position 339 (R339W). Both mutations have been frequently described in other VWM patients. Two-thirds of VWM patients have mutations in eiF2B5. The R113H mutation occurs in approximately 40% of all VWM patients and has been correlated with adult onset and milder clinical manifestation with slower rate of progression of disease. Two cases of R113H/R339W compound heterozygous mutations in VWM patients have been reported previously..
