Marked clinical difference between two sibs affected with juvenile metachromatic leukodystrophy

Abstract

In a child with enzymatically and histopathologically proven metachromatic leukodystrophy (MLD), the disease pursued a course typical of juvenile MLD characterized by neurological degeneration beginning at age 9 years and ending in death at age 18. A younger brother of the patient was found to have profound deficiency of arylsulfatase A in leukocytes and to excrete five- to 20-fold greater-than-normal amounts of sulfatide in the urine. He was completely free of symptoms attributable to MLD until age 16 when he developed acute cholecystitis caused by sulfatide accumulation in the gallbladder. Results of detailed neurological examination at age 21 years were normal; formal psychometric assessment showed a full-scale IQ of 105 (Wechsler). Studies on cultured skin fibroblasts from the brother showed defects in arylsulfatase A activity, measured with the use of synthetic and natural substrates, and in radiolabeled sulfatide turnover. Cellulose acetate gel electrophoresis of fibroblast extracts from the patient showed no detectable arylsulfatase A isozyme under conditions that clearly distinguished pseudo-arylsulfatase A deficiency from classical MLD. Biochemically, the patient was indistinguishable from patients with classical MLD; on the other hand, his clinical course is dramatically more benign than that of his sister who was affected with severe MLD.

Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

“…In 1989, Clarke et al reported two siblings with MLD where one had a much later onset of symptoms as well as a much slower disease progression. 24 In our material, the age of onset was earlier for all three untreated controls, but the disease progression was then equivalent between the sibling pairs. Also, we judge it is more likely that the difference between case controls described in this paper is due to the intervention, rather than because all three pairs happened to have a similar rare intrafamilial variability.…”

Juvenile metachromatic leukodystrophy 10 years post transplant compared with a non-transplanted cohort

“…22 However, substantial variation of phenotype among patients with the same genotype is well known, and may occur even in affected individuals of the same family. 23,24 Therefore, comparing the index patient not only with affected family members, but also with a cohort of untransplanted MLD patients with standardized and validated tools is necessary to substantiate individual findings and evaluate treatment effectiveness. This case exemplifies a follow-up strategy, which helps to identify patients, who will benefit from HSCT more reliably.…”

The relationship of the metachromatic leukodystrophies to neuropsychiatric disorders

“…There are, in fact, only a few reported cases of adult MLD without some evidence for psychiatric manifestations. Behavioral problems and decline in school performance are also common initial signs of juvenile onset MLD (Gordon, 1978;MacFaul et al, 1982;Clarke et al, 1989).…”