Juvenile metachromatic leukodystrophy

Very rare disorders include juvenile metachromatic leukodystrophy, adrenoleucodystrophy, Wilson s disease These conditions are associated with movement disorders, particularly gait disturbance. It is important to attempt to distinguish between primary and secondary (antipsychotic related) movement disorders These conditions are characterized by a progressive loss of cognitive skills (in contrast to the more relative decline seen in schizophrenia and other developmental disorders, where a loss of previously learned skill is unusual)... 

In case of a deficiency of arylsulfatase A, at least one other sulfatase should be measured to exclude multiple sulfatase deficiency (see Chap. 4.1 for the assays of arylsulfatase and other sulfatases). Sulfatide excretion in urine should be measured (see assay below) and/or mutation analysis should to performed to confirm the diagnosis, especially if the clinical symptoms are atypical and in order to exclude a pseudodeficiency of arylsulfatase A. The enzyme should always be measured in the parents to check for the presence of compound heterozygosity of a metachromatic leukodystrophy and a pseudodeficiency allele. This is very important for the interpretation of the results of arylsulfatase A assays, especially when performed in asymptomatic or presymptomatic siblings or in the context of a prenatal diagnosis. Sulfatide should also be measured in case a normal arylsulfatase A activity is found in a patient with symptoms characteristic of (juvenile) metachromatic leukodystrophy. Increased urinary sulfatide excretion is indicative of an activator protein/saposin deficiency (Fig. 4.4.1). 

Several cases of a new form of metachromatic leukodystrophy have been reported (Hahn et al., 1981, 1982 Inui et al., 1983). These cases have clinical symptoms resembling juvenile metachromatic leukodystrophy, but have only about half of the normal arylsulfohydrolase A activity in leukocytes and fibroblasts. The kinetic properties of the arylsulfohydrolase A from fibroblasts are normal. However, the cerebroside 3-sulfate loading test (Porter et al., 1971a) with growing fibroblasts shows an abnormal response, indicating a disturbance in arylsulfatase A activity. Supplementation with the activator (Stevens et al., 1981) of arylsulfatase A results in a normal cerebroside 3-sulfate loading test. This indicates that the new form of metachromatic leukodystrophy is not caused by the deficiency of arylsulfohydrolase A, but rather is caused by a deficiency of the activator protein (Shapiro et al., 1979). Fujibayashi and Wenger (1986) have studied the biosynthesis of sulfa-tide/GMj activator protein in control and mutant cultured skin fibroblasts. Their results indicate that patients with variant form of metachromatic leu-... 

Suzuki, Y., and Mizuno, Y., Juvenile metachromatic leukodystrophy Deficiency of an arylsulfatase A component. J. Pediatr. 85, 824-825 (1974). 

The physiological significance of this kind of activator protein is demonstrated by two fatal lipid storage diseases that are caused by deficiencies of activator proteins rather than of the degrading enzymes variant AB of infantile Gm2 gangliosidosis results from a defect of the Gm2 activator protein (Gonzelmann and Sandhoff, 1978 Hechtman et al., 1982 Hirabayashi et al., 1983), whereas a deficiency of the sulfatide/GMi activator leads to an atypical variant of juvenile metachromatic leukodystrophy (Stevens et al., 1981 Inui et al., 1983). 

Kapaun P, Dittmann RW, Granitzny B, Eickhoff W, Wulbrand H, Neumaier-Probst E, Zander A, Kohlschuetter A. Slow progression of juvenile metachromatic leukodystrophy 6 years after bone marrow transplantation. J Child Neurol 1999 14(4) 222... 

Metachromatic leukodystrophy is due to a defect in arylsulfatase A (ASA). There are three major forms late infantile, juvenile and adult. The overall incidence is 1 40,000. In the late infantile and early juvenile forms, which comprise about 80% of patients, the initial symptoms involve the motor system, with falls, loss of ability to walk, flaccid paralysis, difficulty in swallowing, loss of speech, vision, seizures, decerebrate state and death 1-7 years after onset of symptoms. In the adolescent and... 

In some patients, exhibiting symptoms of the juvenile type of metachromatic leukodystrophy, the disease is caused by a defect in saposin B, an activator that is necessary for full arylsulfatase activity [2]. 

Metachromatic leukodystrophy, juvenile form Arylsulfatase A 22ql3.31-qter 250100... 

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