See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism Approach to the Patient With a Suspected Inherited Disorder of Metabolism Most inherited disorders of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more .
In metachromatic leukodystrophy, arylsulfatase A deficiency causes metachromatic lipids to accumulate in the white matter of the central nervous system, peripheral nerves, kidney, spleen, and other visceral organs; accumulation in the nervous system causes central and peripheral demyelination. Numerous mutations exist; patients vary in age at onset and speed of progression.
The infantile form is characterized by progressive paralysis and dementia usually beginning before age 4 years and resulting in death about 5 years after onset of symptoms.
The juvenile form manifests between 4 years and 16 years of age with gait disturbance, intellectual impairment, and findings of peripheral neuropathy. Contrary to the infantile form, deep tendon reflexes are usually brisk.
There is also a milder adult form.
Diagnosis of metachromatic leukodystrophy is suggested clinically and by findings of decreased nerve conduction velocity; it is confirmed by DNA analysis and/or detecting enzyme deficiency in white blood cells or cultured skin fibroblasts. (Also see testing for suspected inherited disorders of metabolism Initial testing Most inherited disorders of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more .)
There is currently no effective treatment for metachromatic leukodystrophy in patients with advanced symptoms. Bone marrow or stem cell transplantation may stabilize neurocognitive function in mildly symptomatic forms of the disease. Several other therapeutic options are currently being investigated, primarily in late infantile forms of the disease, including gene therapy, enzyme replacement therapy, substrate reduction therapy, and, potentially, enzyme enhancement therapy.
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man® (OMIM®) database: Complete gene, molecular, and chromosomal location information