Disease Spectrum of Early-Onset Neurodegeneration

Background: Neurodegenerative disorders are not restricted to the elderly. There is a considerable number of children and adolescent with progressive neurodegeneration. Key clinical signs are intellectual and motor losses of already attained developmental skills. A couple of hundred different disorders are known; most of them are genetically determined and affect the brain metabolism. Early diagnosis is important especially in those instances when treatment is possible. Due to the impressive advances in biotechnology the identification of the causative genes has improved and led to a continuous expansion of the disease spectrum.

Gray Matter Disorders: The progressive loss of neuronal cells and their derivatives such as photoreceptor cells is the hallmark of neurodegeneration in the gray matter of the central nervous system (CNS). The patients usually present with progressive loss of cognitive and motor as well as visual functions and severe epileptic seizures. MRI reveals a generalized cerebral and cerebellar brain atrophy. Gray matter disorders include Alper’s disease and neuronal ceroid-lipofuscinosis.

White Matter Disorders: Leukoencephalopathies predominantly affect the white matter of the CNS, especially the myelin. Main clinical features comprise motor impairment and spasticity; seizures and cognitive impairment follow later in the course. MRI often reveals characteristic patterns of hypomyelination or demyelination. Classical leukoencephalopathies include Krabbe’s disease, metachromatic leukodystrophy, X-linked adrenoleukodystrophy and Leigh disease.

Treatment: The current treatment is mainly symptomatic. However, the study of long-term known and especially recently identified childhood-onset neurodegenerative disorders has provided wide-ranging insight into the pathogenetic mechanisms of neurodegeneration and sets the basis for providing effective neuroprotective and disease modifying therapies.