Genomic coordinate (human 10,71,816,298 PSAP) & (mouse 10:60,113,449 Psap).
Cytoband (human 10q22.1 PSAP) & (mouse 10qB4 Psap).
Here I present: “Metachromatic Leukodystrophy without Arylsulfatase Deficiency“ Victor McKusick, Mendelian Inheritance in Man’, 1966. (PSAP) icd10=E75.25
INTRODUCTION.
Metachromatic Leukodystrophy (MLD) is a severe genetic disorder causing fatty substances (sulfatides) to build up in the brain, spinal cord, and peripheral nerves, destroying myelin, the nerve’s protective covering. This leads to progressive loss of mental, motor, and physical functions, causing symptoms like walking difficulties, speech problems, seizures, behavioral changes, and eventual paralysis and death, with the age of onset (infantile, juvenile, or adult) affecting progression speed. MLD results from a deficiency in the ARSA enzyme, preventing proper breakdown of lipids, and while there’s no cure, gene therapy and stem cell transplants are being explored.
What It Is
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A lysosomal storage disorderwhere lysosomes, the cell’s recycling centers, lack the enzyme (arylsulfatase A) to break down sulfatides.
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Sulfatides accumulate in cells, damaging the myelin sheath, the insulation around nerve fibers.
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This destruction of white matter (myelin) leads to progressive neurological decline.
Symptoms
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Infantile/Juvenile: Loss of coordination, trouble walking, behavioral issues, difficulty with school, slurred speech, incontinence, paralysis, blindness, hearing loss, seizures.
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Adult: Personality changes (apathy, disinhibition), cognitive decline, memory loss, poor judgment, clumsiness, anxiety, often mistaken for mental illness.
Causes
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Caused by mutations in the ARSA gene (most common) or the PSAP gene, inherited in an autosomal recessive pattern (two mutated copies needed).
Prognosis & Treatment
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A severe, progressive, and ultimately fatal disease, with lifespan varying (3 to 20+ years after onset).
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Early diagnosis generally means faster progression.
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Treatments focus on managing symptoms, with emerging therapies like gene therapy and stem cell transplants showing promise but not yet a cure.
- There is evidence that metachromatic leukodystrophy without arylsulfatase deficiency is caused by mutation in the prosaposin (PSAP) gene encoded on genomic coordinate 10,71,816,298 and cytoband 10q22.1 in humans .
