Diagnosis by whole exome sequencing of atypical infantile onset Alexander disease masquerading as a mitochondrial disorder.

[alexander disease]

There are many similarities , both clinical and radiological , between mitochondrial leukoencephalopathies and Alexander disease , an astrogliopathy . Clinically , both can manifest with a myriad of symptoms and signs , arising from the neonatal period to adulthood . Radiologically , both can demonstrate white matter changes , signal abnormalities of basal ganglia or thalami , brainstem abnormalities and contrast enhancement of white matter structures . Magnetic resonance spectroscopy may reveal elevation of lactate in the abnormal white matter in Alexander disease making the distinction even more challenging .We present a child who was considered to have an infantile onset mitochondrial disorder due to a combination of neurological symptoms and signs (developmental regression , failure to thrive , episodic deterioration , abnormal eye movements , pyramidal and cerebellar signs ), urinary excretion of 3 -methyl-glutaconic acid and imaging findings (extensive white matter changes and cerebellar atrophy ) with a normal head circumference . Whole exome sequence analysis was performed .The child was found to harbor the R 416 W mutation , one of the most prevalent mutations in the glial fibrillary acidic protein (GFAP ) gene that causes Alexander disease .Alexander disease should be considered in the differential diagnosis of infantile leukoencephalopathy , even when no macrocephaly is present . Next generation sequencing is a useful aid in unraveling the molecular etiology of leukoencephalopathies .

Diseases
Validation

Diseases presenting "abnormal eye movements" symptom

alexander disease

pyruvate dehydrogenase deficiency

x-linked adrenoleukodystrophy

This symptom has already been validated