Alexander Disease have first described by a New Zealand pathologist Doctor William Stewart Alexander in year 1949. This disease have divided into three forms according to the age of onset. This types are infant, young and adult forms also. All these forms are rare, but the rarest type is adult-onset Alexander syndrome.
Alexander disease has an autosomal recessive or autosomal dominant inheritance. The mutation have reported in glial fibrillary acidic protein (GFAP) gene on chromosome 17.
The symptoms will usually start in the first two years of life. Some of these children may die in the first year of life. However, some of these patients may live up tp 10 years of age.
The first finding is motor development delaying. With it, megalencephaly, bulbar findings, spasticity and cognitive deficits will seen also. The head circumference will seen often enlarged. Children that have hydrocephalus will usually develop raised intracranial pressure and cause to rapidly progress of the disease. Resulting in severe mental retardation and spastic quadriparesis that involves all four limbs. Severe convulsion attacks have reported in these patients, that have resistant to medicines also. Nutrition often becomes a problem and feeding tubes such as nasogastric tube may necessary.
The starting age is generally between 4 to 10 age. This form have characterized by speech and swallowing difficulty. Vomiting have reported commonly also. These patients may have weakness and spasticity in extremities, especially on the legs. Mental functions may slowly diminish. But in some cases intellectual skills remain intact. With it, mental ability and head size can be normal. Pathologically, the baby form of this disease usually affects the brain. But the childhood form affects the brain stem more, rather than brain. With it, myelin deficiency is less pronounced than infantile form also. All this disease symptoms are similar like Canavan Disease also.
This form usually have mild progress than the other two forms. Symptoms may start in youth. Sometimes, does not affect the patient until death. In elderly patients, ataxia, speech disorders, swallowing and sleeping disorders may occur. Symptoms may resemble with multiple sclerosis or tumors.
The demonstration of glial fibrillary acidic protein (GFAP) gene mutation by molecular genetic tests will give the definite diagnosis.
In brain magnetic resonance cerebral white matter abnormalities may seen that affects the frontal region white matter symmetric.
Infantile type alexander disease is the most severe progressed type. Some of these patient will die before 10 years of age. With it, some of them will live up to middle age about 40-45 of age. Childhood and Adult-onset disease may live longer. Some of these patient will live asymptomatic until they die because of an another disease.