USMLE Step 1 Pathology 2025 – 400 Free Practice Questions to Pass the Exam

Metachromatic leukodystrophy is a lysosomal storage disorder caused by a deficiency in the enzyme arylsulfatase A. This deficiency leads to the accumulation of sulfatides, which in turn cause demyelination of the nervous system. The disease generally presents in early childhood, often between the ages of 1 and 2, and it is characterized by progressive neurological deterioration, loss of motor skills, and cognitive decline. Many affected children do not survive beyond the first decade of life due to severe complications arising from the progressive nature of the disease, including respiratory failure and infections.

In contrast, Tay-Sachs disease typically presents with neurodegeneration in infancy, but many individuals live into their early childhood years, typically beyond the first decade, before succumbing to the disease. Gaucher's disease can present in various forms, including a later-onset variant, and while it can have serious complications, individuals can live well into adulthood. Niemann-Pick disease, while also a serious condition that may lead to early death, has a different underlying pathology and is more variable in its progression compared to metachromatic leukodystrophy. Thus, the characteristic early and fatal progression of metachromatic leukodystrophy within the first decade