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 "neonatal period" symptom

alexander disease

alpha-thalassemia

benign recurrent intrahepatic cholestasis

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cutaneous mastocytosis

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

harlequin ichthyosis

hirschsprung disease

homocystinuria without methylmalonic aciduria

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neonatal adrenoleukodystrophy

neuralgic amyotrophy

pyruvate dehydrogenase deficiency

zellweger syndrome

You can validate or delete this automatically detected symptom