Alexander disease


[William Stewart Alexander, New Zealand pathologist, 1919-2013]
ABBR: AD One of four rare, inherited leukodystrophy syndromes, the most common types of which occur in infancy or early childhood.

The disease is exceptionally rare; about 500 cases have been reported.

Abnormal filaments, i.e., Rosenthal bodies, accumulate in astrocytes. These result from an autosomal dominant gain-of-function mutation of glial fibrillary acidic proteins (GFAPs).

Type 1 (the early-onset form of AD) produces enlargement of the infant's head (megalocephaly), along with failure to achieve neurological and psychiatric milestones and the occurrence of spasticity, failure to thrive, seizures, dementia, and, typically, early loss of life (by age 14).

This disease is diagnosed by the presence of abnormal white matter signal changes on magnetic resonance imaging or spectroscopy. A crude diagnosis may be made through clinical symptoms (including macrocephaly). Brain biopsy specimens from patients show the accumulation of abnormal inclusion bodies within astrocytes.

There is no cure or standard therapy for AD, but it may respond to medications (such as ceftriaxone) that affect GFAP. However, care for most patients is supportive.

The prognosis is poor. With early onset, death usually occurs within 10 years; generally, the later the disease occurs, the slower its course.

Seizures associated with AD are managed with anticonvulsant drugs. Genetic counseling may be useful for family members although most cases of the disease are inherited sporadically. Consultations with a psychologist may help with behavioral difficulties. Speech therapists may help infants and children with feeding and language use.