Transcript for:
Understanding Metachromatic Leukodystrophy (MLD)

Metachromatic leukodystrophy (MLD) is a rare, inherited disease that damages the brain and peripheral nerves due to an accumulation of fatty substances called sulfatides. This buildup results from a deficiency of the enzyme arylsulfatase A, which is crucial for breaking down sulfatides. MLD is a progressive and typically fatal disease, leading to deterioration of motor and cognitive functions. [1, 2, 3, 4, 5] Here's a more detailed explanation: [3, 6] What causes MLD? [3, 6] * MLD is caused by a genetic mutation, specifically a problem with the ARSA gene, which provides instructions for making the arylsulfatase A enzyme. [3, 6] * This enzyme deficiency leads to the accumulation of sulfatides, which damages the myelin sheath that protects nerves. [6, 7] * The lack of myelin disrupts the normal functioning of nerves, leading to progressive neurological decline. [6, 7] Symptoms of MLD: [8, 9] * Symptoms vary depending on the age of onset (late infantile, juvenile, or adult). [8, 9] * Common symptoms include: [1, 10] * Developmental delays [1, 10] * Muscle weakness and stiffness [10, 11] * Loss of motor skills, including the ability to walk [1, 2] * Cognitive decline and dementia [1, 10] * Seizures [1, 10] * Vision and hearing loss [1, 11] * Incontinence [1] * Paralysis [10, 11] * Difficulty swallowing [10, 11] * Personality and behavioral changes [2, 12] Diagnosis and Treatment: [1, 13, 14, 15, 16] * MLD is diagnosed through genetic testing and enzyme activity measurements. [1, 13, 14, 15, 16] * There is currently no cure for MLD, but treatments focus on managing symptoms and improving quality of life. [1, 17] * These may include physical and occupational therapy, as well as medications to address seizures and other complications. [1, 17, 18, 19, 20] * Research is ongoing into potential treatments, including gene therapy and bone marrow transplantation. [15, 17] Types of MLD: [9, 10] * Late-infantile MLD: Symptoms appear in the first few years of life and progress rapidly, often leading to death by age 5. [9, 10] * Juvenile MLD: Symptoms appear between 4 and 16 years of age and progress more slowly than late-infantile MLD. [9, 21, 22] * Adult MLD: Symptoms appear in adulthood and progress more slowly than other forms of MLD. [2, 9, 12, 17] Prognosis: [5, 23] * MLD is a progressive and ultimately fatal disease, with a shorter-than-normal lifespan for individuals affected. [5, 23] * The earlier the age of onset, the more rapidly the disease progresses. [23] * The disease course varies depending on the specific type of MLD and the individual. [2, 24] Generative AI is experimental. [1] https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/ [2] https://rarediseases.org/rare-diseases/metachromatic-leukodystrophy/ [3] https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy [4] https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/symptoms-causes/syc-20354733 [5] https://med.umn.edu/pediatrics/programs-centers-institutes/leukodystrophy-center/metachromatic-leukodystrophy [6] https://www.chp.edu/our-services/rare-disease-therapy/conditions-we-treat/metachromatic-leukodystrophy [7] https://www.ukri.org/who-we-are/how-we-are-doing/research-outcomes-and-impact/mrc/mrc-funded-discovery-science-underpins-gene-therapy-cures/ [8] https://www.ncbi.nlm.nih.gov/books/NBK1130/ [9] https://www.merckmanuals.com/home/children-s-health-issues/hereditary-metabolic-disorders/metachromatic-leukodystrophy [10] https://en.wikipedia.org/wiki/Metachromatic_leukodystrophy [11] https://www.prepladder.com/neet-pg-study-material/pathology/metachromatic-leukodystrophy-cases-symptoms-diagnosis-and-treatment [12] https://pmc.ncbi.nlm.nih.gov/articles/PMC543838/ [13] https://rarediseases.org/rare-diseases/metachromatic-leukodystrophy/ [14] https://www.uptodate.com/contents/metachromatic-leukodystrophy [15] https://pmc.ncbi.nlm.nih.gov/articles/PMC7606900/ [16] https://www.prepladder.com/neet-pg-study-material/pathology/metachromatic-leukodystrophy-cases-symptoms-diagnosis-and-treatment [17] https://ufhealth.org/conditions-and-treatments/metachromatic-leukodystrophy/patient-education [18] https://medlineplus.gov/ency/article/001205.htm [19] https://drdeepakaiims.com/leukodystrophies-what-is-it-types-symptoms-treatment/ [20] https://www.sprintdiagnostics.in/hyderabad/test/aryl-sulfatase-a-test [21] https://www.youtube.com/watch?v=ekLLYT-LKGI [22] https://en.wikipedia.org/wiki/Metachromatic_leukodystrophy [23] https://www.mountsinai.org/health-library/diseases-conditions/metachromatic-leukodystrophy [24] https://pmc.ncbi.nlm.nih.gov/articles/PMC4301611/