Pseudo-arylsulfatase A deficiency
Type of disease: Rare conditions
Pseudo-arylsulfatase A deficiency is when an individual carries genetic changes that cause a serious condition known as metachromatic leukodystrophy (MLD), but experiences none of the symptoms (asymptomatic) that are characteristic of that illness. Metachromatic leukodystrophy is one of many lysosomal storage disorders (please see: Lysosomal disorders). It is a progressively worsening inherited disorder, affecting the brain and spinal cord, characterized by the accumulation of fats within the cells called sulfatides. Both conditions are caused by genetic changes in either the ARSA or the PSAP genes which reduce the amount of arylsulfatase A (ASA) enzyme, a protein which functions to break down sulfatides. The accumulation of these sulfatides is what causes the symptoms associated with MLD including deteriorating brain function over time, losing the ability to walk or speak, seizures and more. In pseudo-arylsulfatase deficiency, though there is also a decrease in enzyme function, the cells still manage to breakdown the sulfatides thus preventing the damaging effects of build up. MLD can onset in late infancy, late childhood, or adulthood. Because measuring the individual’s enzyme activity will show decreased function regardless of which condition they have, it is difficult to determine when or if symptoms will present. Diagnosis involves genetic and other testing in addition to enzyme function analysis to differentiate the types.
MLD and pseudo-arylsulfatase deficiency are inherited or passed through families in an autosomal recessive manner. This means that two copies of the changed gene are needed to produce the symptoms. In recessive conditions, each parent is an unaffected carrier. Each of their children has a 25% chance of being affected. A genetic counselor can provide further understanding of the inheritance and risks to future pregnancies.