Juvenile Alexander Disease: A Rare Leukodystrophy

Abstract

Alexander disease is an uncommon autosomal dominant leukodystrophy that influences the white matter of the central nervous system (CNS), predominantly affecting the frontal lobe bilaterally. The most obvious pathogenic hallmark is the extensive deposition of cytoplasmic inclusions known as "Rosenthal fibers" in perivascular, subpial, and subependymal astrocytes throughout the CNS. The hereditary cause is mutations in the glial fibrillary acidic protein (GFAP) gene. Infantile, adult, and juvenile onsets are the three subtypes. Psychomotor retardation, mile-stone regression, spastic paresis, brain stem symptoms (swallowing, speech, etc.), and seizures define the juvenile variety, which emerges between the ages of three and 10 years. Macrocephaly has a lower likelihood of being a juvenile type. It is generally diagnosed based on clinical and magnetic resonance imaging findings. A five-year-old girl is presented as a case of juvenile Alexander disease, with typical clinical and MRI features.

Alexander Disease: Screening andin silicofunctional characterization of variants on candidate gene

“…Type 1 is the early onset and most severe form of Alexander disease predominantly characterized by: seizures, macrocephaly, motor and developmental delay, failing to thrive Paroxysmal degeneration, encephalopathy and typical brain MRI. Type 2 is present across the life span and has predominant features such as: eye movement abnormality, palatal clonus, bulbar involvement, autonomic dysfunction cognitive and other neurological deficiencies 1213 .…”

“…However, on finding overlaps between the age dependent subtypes especially between juvenile (onset 2-14 years of age) and adult (late juvenile to adult) a revised classification has divided AxD into two subtypes: Type1 and Type2 2 . The infantile type I AXD are more frequent and accounts 51 % of the total AXD cases, these appears before 2 years of age and the children can live anywhere from a few days after birth to around the age of 8 to 10 years 12 . The physiological condition of juvenile AXD includes macrocephaly and psychomotor delay followed by regression, spastic parapresis and feeding difficulty.…”

Teenager With Recurrent Ataxia, Ophthalmoplegia, and Encephalopathy Associated With Demyelination

“…Though not consistently found, he did lack suggestive features including widespread frontal white matter involvement, medullary involvement, and periventricular rim abnormalities (hyperintense on T1-weighted imaging and hypointense on T2). 5 Late-onset Leigh syndrome is a mitochondrial disorder that may present with ataxia and episodic neurodegeneration triggered by infection, which can stress various metabolic disorders. 6 Large basal ganglia and brainstem abnormalities are typical, but our patient's ovoid supratentorial lesions, MRS, and presence of oligoclonal bands were not characteristic.…”

Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia—The Neonatal Type of Alexander Disease

“…Histopathological identification of RFs confirmed AxD diagnosis before the era of genetic testing. The pathological process involves the white matter of frontal lobes and less extensively temporal lobes [ 5 , 7 , 9 , 10 ].…”

“…The juvenile form is revealed in school-age children with features such as bulbar and pseudobulbar signs (dysphasia, dysarthria), ataxia, spasticity with possible epilepsy, and intellectual disability. Patients with this form of AxD are normocephalic, and the progression of the disease is milder than in previous types, with surveillance rates ranging from early adolescence to 30 years [ 1 , 9 ]. Adult form, much less frequent than other types, is characterized by variable clinical presentation with progressive ataxia, quadriparesis, eye movement abnormalities, palatal myoclonus, dysautonomia, and postural defects.…”