Metachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system).
Causes: Metachromatic leukodystrophy (MLD) is usually caused by the lack of an important enzyme called arylsulfatase A. Because this enzyme is missing, chemicals called sulfatides build up in and damage the nervous system, kidneys, gallbladder, and other organs. In particular, the chemicals damage the protective sheaths that surround nerve cells. The disease is passed down through families (inherited). You must get a copy of the defective gene from both your parents to have the disease. Parents can each have the defective gene, but not have MLD. A person with one defective gene is called a "carrier." Children who inherit only one defective gene from one parent will be a carrier, but usually will not develop MLD. When two carriers have a child, there is a 25% chance that the child will get both genes and have MLD. Late infantile MLD symptoms usually begin by ages 1 - 2.
Symptoms: Juvenile MLD symptoms usually begin between ages 4 and 12, Abnormal high muscle tone, abnormal muscle movements, Behaviour problems, Decreased mental function, Decreased muscle tone, Difficulty walking, Feeding difficulties, Frequent falls, Inability to perform normal tasks, Incontinence, Irritability, Loss of muscle control, Nerve function problems, Personality changes, Poor school performance, Seizures, Speech difficulties, slurring, Swallowing difficulty.
Diagnosis: Tests that may be done include: Blood or skin culture to look for low arylsulfatase A activity, Blood test to look for low arylsulfatase A enzyme levels, CT scan, DNA testing for the ARSA gene, MRI, Nerve biopsy, Nerve signalling studies, Urinalysis, Urine chemistry.
Treatment: There is no cure for MLD. Care focuses on treating the symptoms and preserving the patient's quality of life with physical and occupational therapy.
Prevention: Genetic counselling is recommended if you have a family history of this disorder.
A special programme for the diagnosis and prevention of lysosomal storage diseases (LSD) was developed in the former USSR. All the patients from 814 families at risk were investigated using biochemical techniques. In total, 363 patients with mucopolysaccharidoses (MPS), mucolipidoses, glycoproteinoses, sphingolipidoses and other LSD were diagnosed; 55 families at risk sought prenatal diagnosis and 67 fetuses were investigated for MPS (types I, II, IIIA and IIIB, VI), Tay-Sachs disease, Sandhoff disease, GM1-gangliosidosis, metachromatic leukodystrophy, mannosidosis, Gaucher disease and multiple sulphatidosis; 17 affected fetuses were diagnosed and aborted. There was an ethnic distribution of different lysosomal storage diseases in the former USSR.