Clinical and Genetic Study of Children with White Matter Diseases

Abstract

Background: White matter disorders or leukoencephalopathies comprise all disorders that exclusively or predominantly cause affection of the white matter of the brain. Leukodystrophies (LDs) are genetically determined leukoencephalopathies, which can occur at all ages, be progressive or static, and be genetic or acquired. Many leukodystrophies are degenerative in nature, their clinical course is mostly progressive. Aim of the study: (1) To determine molecular background of some white matter diseases (2) To determine phenotype genotype correlation of white matter diseases. Patients and methods: In this study, we describe the clinical, neuro-radiological and molecular findings of 115 patients with white matter diseases. Age spectrum is from six months to 12 years old, putting in consideration the correlation of white matter development with age during the first 2 years of life. Brain MRI demonstrated deep white matter affection in all patients that varied in severity and distribution. Molecular genetic studies were performed for patients suspected clinically to have Canavan disease (ASPA gene), X-linked adrenoleukodystrophy (ABCD1 gene) megalencephaly leukoencephalopathy and cortical cyst (MLC1 gene and HEPACAM gene), Metachromatic leukodystrophy (ARSA gene) and Pelizaeus Merzbacher disease (PLP1gene). Results: Canavan disease encountered the most common neurodegenerative disorder in our study (22.6%). Conclusion: we present a large cohort of patients with the characteristic clinical and brain imaging findings of white matter diseases. Moreover, we create current useful, algorithms for white matter diseases hoping to be helpful for the treating neuropediatricians and neurologists to make a definitive diagnosis and to decrease burden to patients and families with uneventable investigations who usually are deteriorating from a severe and progressive neurological syndrome