Metachromatic Leukodystrophy: A Comparative Study of the Ultrastructural Findings in the Peripheral Nervous System of Three Cases, One of the Late Infantile, One of the Juvenile and one of the Adult Form of the Disease

Abstract

The ultrastructural findings in the peripheral nerve of three cases of M. L. D., namely of the late infantile, the juvenile and the adult form are described. The pathological changes consist of two phenomena: segmental demyelination and lysosomal storage of sulfatides, both probably separate results of a deficiency of the enzyme Arylsulfatase A. Some differences are found in the degree of segmental demyelination and the type of lysosomal storage products. A possible relation between these differences and the supposed difference in the defect of the enzyme Arylsulfatase A, responsible for the different subtypes of the disease, is postulated.

Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

“…Histopathologic evaluation of nerve biopsy specimens has been an important diagnostic tool for MLD patients in the past, but can also enhance our understanding of disease pathogenesis nowadays. An overview of the published peripheral nerve abnormalities in different MLD studies is presented in (Additional file 3: Table S2) [5, 31, 42-46, 53, 55-63].…”

“…Besides, some studies found that tuffstone bodies are more frequent in late-infantile MLD, while zebra bodies are more frequent in juvenile and adult MLD. However, whether different inclusion body types have different roles in disease pathogenesis is unclear as different types can blend into each other and most likely reflect different orientations and packing of metachromatic material instead of different disease mechanisms [5, 56].…”

“…Rare congenital and early-infantile types have also been reported [4]. Levels of residual ASA activity correlate with the type and severity of symptoms [5, 6]. Diagnosis of MLD is confirmed by demonstrating deficient ASA activity in leukocytes, increased urinary sulfatide levels, and pathogenic ARSA variants.…”

Insight into adult-onset metachromatic leukodystrophy with optic atrophy: A comprehensive case report

“…There are 3 main clinical types of MLD which are as follows: late-infantile (age of onset before 30 months), juvenile (age of onset between 2.5 and 16 years), and adult onset (age of onset after 16 years) [6] . The type and severity of the symptoms of MLD correlate with the levels of residual ASA activity [ 4 , 5 ].…”

“…MLD is named from the presence of metachromatic granules in the affected cells, formed as a result of the accumulation of sulfatide and sphingolipids in myelin [3] . The type and severity of the symptoms of MLD correlate with the levels of residual ASA activity [ 4 , 5 ]. There are 3 main clinical types of MLD which are as follows: late-infantile (age of onset before 30 months), juvenile (age of onset between 2.5 and 16 years), and adult-onset (age of onset after 16 years) [6] .…”