Metachromatic leukodystrophy is an autosomal recessive lysosomal storage disease consisting of progressive demyelination of the peripheral and central nervous systems. In most patients, it is attributed to a mutation in the arylsulfatase A (ARSA) gene, which in turn hinders the production of arysulfatase A. This enzyme is necessary for the desulfation of cerebroside, a glycolipid of myelin.
There are three subtypes of metachromatic leukodystrophy. The clinical presentation is dependent on the subtype.
Workup of metachromatic leukodystrophy consists of a history and physical exam, nerve conduction testing, cerebrospinal fluid (CSF) evaluation, and imaging tests. A definitive diagnosis can be established with genetic testing.
The diagnosis of metachromatic leukodystrophy is established by demonstrating reduced arylsulfatase A gene activity in cultured skin fibroblasts or leukocytes. However, a diagnosis based only on the activity of ARSA should be differentiated from ARSA pseudodeficiency, which is present in about one percent of the population . Arylsulfatase A pseudodeficiency can be differentiated form metachromatic leukodystrophy by performing a radiolabeled sulfatide fibroblast loading test, assessment of sulfatide levels in the urine, and/or genetic analysis for mutations .
Prenatal testing can be performed by measurement of arylsulfatase A activity to identify carriers. Newborn screening is done using immune-quantification assays which screen numerous lysosomal proteins .
Magnetic resonance imaging (MRI) shows symmetric lesions in the white matter; lesions are predominant in the periventricular region during the early stages of the disease  . Late stage disease is characterized by cortical atrophy  . Results of clinical trials have shown that N-acetylaspartate levels, which are measured by magnetic resonance spectroscopy, may act as a marker of disease progression .
Nerve conduction studies demonstrate reduced nerve conduction velocity; in the early stages of the disease, sensory potentials are affected more severely than motor responses  . A peripheral nerve biopsy, which is often not necessary for diagnosis, is characterized by segmental demyelination with metachromatic material in schwann cells and macrophages. Neurocognitive and neuropsychological testing may be performed when clinically indicated.