We, consequently, evaluated the differential impact of D313Y on clinical manifestations and concluded that D313Y might broaden the spectrum of hereditary small artery diseases of the brain which preferably occur,45 years of age and should be more specifically taken into account in patients with multifocal WML in the absence of classical risk factors. The widespread availability of MRI has resulted in an increased recognition that WML are common incidental findings in elderly individuals.65 years of age, but have rarely be seen as early as in the third and fourth life decades. Although the clinical relevance of such MRI findings primarily depends on the respective etiology, even incidentally discovered WML are frequently reported to be associated with various neurological symptoms, e.g. progressive cognitive and neurobehavioral deficits, gait and balance disturbances, epileptic seizures, or depression. In general, WML show a strong correlation with a wide range of neurodegenerative and neuropsychiatric disorders, independent of other risk factors. Specific treatment is available for some of the underlying causes, which effectively could modify symptoms and prognosis, e.g. some metabolic and inflammatory disorders. Furthermore, the cerebral lesions are often irreversible, and thus the underlying etiology is particularly important to consider. However, in clinical practice, uncovering the underlying etiology of WML in adults without cardiovascular risk factors remains dissatisfying in most of the cases. There are many different causes of WML, which can occur at all ages, be progressive or static, and be genetically determined or acquired. The diagnostic workup is complicated as many different analyses have to be performed, at high financial costs as well as emotional stress and often with disappointing results. With more widespread use of neuroimaging, neurologists will increasingly be confronted with WML in younger adults. In recent years, a considerable number of new sporadic or hereditary small artery diseases of the brain have been detected which preferably occur,45 years of age. FD is one of those hereditary diseases that can cause cerebral AbMole Hexyl Chloroformate vasculopathy. Apart from macroangiopathic changes, FD is frequently associated with early microangiopathic brain alterations with progressive WML. However, the typical FD symptom complex includes further manifestations such as cornea verticillata or angiokeratoma, renal or cardiac manifestations, strokes and peripheral neuropathy. Of note, strokes are highly important for Fabry diagnosis, because they often occur before FD is readily diagnosed and in absence of other clinical events. Although most patients present with the classical phenotype, ����variant���� forms with prominent cardiac or renal manifestations have been described. Whether these mono- or oligo-organic phenotypes are associated with specific mutations remains unclear. In fact, efforts to associate genotype with clinical phenotype have been largely unsuccessful. In the current study, we report on a family carrying the GLA D313Y mutation and being affected by a potentially exclusive neurologic manifestation of the CNS with multifocal WML, in the absence of other FD-specific symptoms. The diagnosis was further supported by the reduced intraepidermal nerve fiber density in the index patient, which is also known as afrequentandearlymanifestation ofFD.D313Yresulted innormal GLA enzyme activities in leukocytes and severely decreased activities in plasma.