# Description of the Hamburg Alexander Leukodystrophy Cohort—Insights into Practical Classification and the Care Situation

## TL;DR

This paper describes the care and symptoms of nine Alexander disease patients, highlighting the disease's variability and the potential benefit of steroid treatment.

## Contribution

The study provides practical classification features and insights into the heterogeneous care needs of Alexander disease patients.

## Key findings

- Alexander disease shows a broad spectrum of phenotypes, with apnoea being a common symptom.
- Steroid treatment reduced symptoms in two patients, suggesting potential therapeutic benefit.
- Key features like feeding problems and epilepsy were identified to assess disease severity.

## Abstract

Background: Alexander disease (AxD) is a rare severe leukodystrophy that has no cure to date. A pathogenic gain-of-function variant in the GFAP gene affects the astrocytes and subsequently the function of the white matter in the CNS. Methods: We retrospectively analyzed the most frequent symptoms of nine AxD cases, classified them according to published classifications, and described the need of care and support. Results: The description of the courses of disease of nine cases with AxD reflects the broad spectrum of different phenotypes of AxD, with often occurring apnoea. Data about care and support for AxD patients indicate a high and heterogeneous need of support. Treatment with steroids reduced symptoms in two patients. Some patients showed lasting improvement during their course of disease. Conclusions: The course of AxD is very heterogeneous. Thus, we extracted relevant key features to describe the severity of the disease, namely feeding problems, epilepsy, age-appropriate motor function, failure to thrive, age-appropriate language and apnoea. We recommend early evaluation for clinical care and support. For some AxD patients, treatment with steroids may alleviate symptoms. Further development of efficient treatments is necessary.