Metachromatic leukodystrophy, the causes and symptoms
When planning to have a child, even before pregnancy, prospective parents can investigate their own risk of passing on genetic diseases to their children by undergoing preconception testing. In this way, they can find out if they unknowingly are healthy carriers of some hereditary disease, such as rare recessive genetic disorders (X-fragile syndrome, metachromatic leukodystrophy, Duchenne syndrome).
Recessive genetic diseases arise when both parents carry recessive mutations of the same gene. In this case, children have a 1 in 4 chance of being sick 1 .
Metachromatic leukodystrophy rare and autosomal disease
La metachromatic leukodystrophy, also known as Scholtz disease or arylsulfatase deficiency, is an autosomal recessive rare disease that affects 1 in every 625 individuals.000 2 . It is a lysosomal storage disease classified in the’sphere of leukodystrophic diseases, that is, diseases related to the growth and development of melina (forming the lining of neurons) 2,3 .
The disease develops due to a gene mutation ARSA, located on the long arm of chromosome 22. This alteration is responsible for a deficiency of arylsulfatase A, an enzyme involved in the metabolism of sulfatides, i.e., substances that make up the myelin sheath of neurons. In the individual with this mutation, production of arylsulfatase A is reduced or absent, and sulfatides accumulate in the kidneys and central nervous system, causing patients to lose cognitive and motor skills 2,3 .
Metachromatic leukodystrophy is diagnosed by demonstrating a lack of sulfatide metabolism, by observing theaccumulation of the same in the urine and nerves, and with genetic analysis 3 .
We can distinguish between four forms of metachromatic leukodystrophy, considering age of onset and symptomatology:
- late childhood, affecting the subject between the ages of 6 months and 2 years;
- juvenile-early, between the ages of 4 and 6 years;
- juvenile-delayed, developing by age 12 years;
- adult age, after the age of 12 years.
The first three types are the most serious, as individuals can no longer speak or walk properly and, in the final stage, have difficulty even swallowing. The child’s death usually occurs a few years after diagnosis. The type that arises in adulthood is milder and with slow progression. What all types have in common is the gradual deterioration of motility and neurocognitive functions 3,4 .
Metachromatic leukodystrophy is incurable, to date, and for that reason is considered a terminal disease. There are some therapies aimed at the slowing of symptoms, such as gene therapy and enzyme replacement therapy (ERT) 5 .
Potentially heritable genetic diseases are indeed many, which is why couples planning to have a child should consider undergoing a preconception genetic test in order to know their reproductive risk. The Igea preconception test allows the discovery of the percentage of risk of having children with a genetic disease, even a rare one, such as metachromatic leukodystrophy.