Type I Alexander disease: Update and validation of the clinical evolution-based classification

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

“…Patients with Alexander Disease present variable clinical presentations and prognosis, with non-obvious phenotype–genotype correlation [ 11 , 14 , 16 ]. Therefore, in AxD, not only genetic tests but also the age of disease onset and clinical features, including findings in brain MRI, are crucial in the diagnostic process and prognosis.…”

“…Therefore, in AxD, not only genetic tests but also the age of disease onset and clinical features, including findings in brain MRI, are crucial in the diagnostic process and prognosis. This explains the rapid development of new clinical classifications of AxD in recent years, which sometimes may be confusing and need explanation [ 4 , 16 ].…”

“…Both these classifications lacked a neonatal type distinguished from variable infantile AxD, which was proposed by Springer et al [ 11 ]. This separation is necessary due to a uniform pattern of severe clinical presentation in neonatal AxD [ 10 , 11 , 14 , 16 , 18 , 19 ]. To date, the neonatal form was described only in approximately 20 patients [ 14 , 16 , 19 ].…”

“…This separation is necessary due to a uniform pattern of severe clinical presentation in neonatal AxD [ 10 , 11 , 14 , 16 , 18 , 19 ]. To date, the neonatal form was described only in approximately 20 patients [ 14 , 16 , 19 ]. Therefore, we provided a detailed description of the neonatal type of AxD with rapid progression to expand the clinical spectrum of AxD.…”

“…Moreover, due to the early, severe progression of the disease, patients characterize a lack of developmental progression with the absence of postural acquisitions. Other typical symptoms include hypotonia, vomiting, and failure to thrive [ 10 , 11 , 16 , 18 , 19 ]. Unlike the infantile type, prominent spasticity, ataxia, or upper motor symptoms are not observed in neonatal AxD.…”