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Metachromatic leukodystrophy (MLD) is a rare and life-threatening inherited disease of the body’s neurometabolic system1,2

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Metachromatic leukodystrophy (MLD) is a rare and life-threatening inherited disease of the body’s neurometabolic system1,2

MLD is an autosomal recessive disease and a lysosomal storage disorder caused by the lack of an enzyme called arylsulfatase A (ARSA)1

MLD is both a neurometabolic disorder and a leukodsytrophy that leads to progressive loss of motor function and cognitive skills, dysphagia, seizures, severe neurological disability, and ultimately death.1,3-5

Because patients with MLD progressively lose motor and cognitive function and some may never achieve the ability to walk, caregivers tend to spend an average of 15 hours per day caring for an affected child.4,6

Listen to one mother share the impact MLD had on her daughter

Lysosomal storage disorders come in many forms and cause toxic materials to build up in cells7

Caused by a pathogenic mutation in the ARSA gene, MLD results in the accumulation of sulfatides in various tissue types:2,8,9
  • The buildup of sulfatides causes the breakdown of the myelin sheath and damages nerve fibers2,10
  • New lysosomal storage disorders continue to be identified7

The role of the ARSA enzyme in the body

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Physiologic
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Sulfatides are major components of the myelin membrane.11
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The role of the ARSA enzyme is to break down sulfatides in the lysosome.10
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Pathologic
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MLD occurs when there are variants in the ARSA gene, causing a deficiency of the ARSA enzyme and decreasing the breakdown of these sulfatides.1,8
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This accumulation of sulfatides leads to demyelination (damage to the myelin sheath) and neurodegeneration (decline of the nervous system).1,8

MLD mainly affects children, but has different subtypes based on age of symptom onset9,12

It is critical to diagnose MLD early before the disease progresses, as MLD is fatal if left untreated.2 Patients may appear healthy at birth, but age of first symptoms can range from anywhere under 30 months to 17 years old.4,9 The average survival is 4.2 years for late infantile (birth to 30 months) and 17.4 years for early juvenile patients (30 months to 7 years old).2

MLD is an autosomal recessive disease, so if both parents are carriers, there is a probability of their child being affected13

Autosomal recessive hcp rev

Hear from one mother about why genetic testing was so critical to her family

How rare is MLD and who does it affect?

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Population details
1 in 100 people are carriers of the ARSA mutation that can cause MLD.16

ARSA, arylsulfatase A.

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Patients with pre-symptomatic late infantile, pre-symptomatic early juvenile, and early symptomatic early juvenile MLD may have a treatment option.
Learn more now
How to identify initial symptoms

References: 1. Biffi A, Cesani M, Fumagalli F, et al. Metachromatic leukodystrophy-mutation analysis provides further evidence of genotype-phenotype correlation. Clin Genet. 2008:74;349-357. 2. Mahmood A, Berry J, Wenger DA, et al. Metachromatic leukodystrophy: a case of triplets with the late infantile variant and a systematic review of the literature. J Child Neurol. 2010;25(5):572-580. 3. Lamichhane A, Cabrero RF. Metachromatic leukodystrophy. In: StatPearls [internet]. StatPearls Publishing; January 2024. Accessed April 4, 2025. https://www.ncbi.nlm.nih.gov/books/NBK560744/. 4. Kehrer C, Elgun S, Raabe C, et al. Association of age at onset and first symptoms with disease progression in patients with metachromatic leukodystrophy. Neurology. 2021(96):e255-e266. 5. Eichler F, Sevin C, Barth M. Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy. Orphanet J Rare Dis. 2022;17:370. 6. Lin G, Suh K, Fahim SM, et al. Atidarsagene autotemcel for metachromatic leukodystrophy. Institute for Clinical and Economic Review; October 30, 2023. Accessed April 4, 2025. https://icer.org/assessment/metachromatic-leukodystrophy-2023/#timeline 7. Lysosomal storage disorders. National Organization for Rare Disorders. Accessed April 4, 2025. https://rarediseases.org/rare-diseases/lysosomal-storage-disorders/ 8. Gieselmann V, Krägeloh-Mann I. Metachromatic leukodystrophy – an update. Neuropediatrics. 2010;41:1-6. 9. Wang RY, Bodamer OA, Watson MS, et al. Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. Gen Med. 2011:13;457-484. 10. Metachromatic leukodystrophy. Cleveland Clinic. Accessed April 4, 2025. https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy 11. Jeon SB, Yoon HJ, Park SH, Kim IH, Park EJ. Sulfatide, a major lipid component of myelin sheath, activates inflammatory responses as an endogenous stimulator in brain-resident immune cells. J Immunol. 2008;181(11):8077-8087. 12. Gomez-Ospina N. Arylsulfatase A deficiency. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews® [internet]. University of Washington; 1993-2024. Revised April 25, 2024. Accessed April 4, 2025. https://www.ncbi.nlm.nih.gov/books/NBK1130/ 13. About MLD. MLD Support Association UK. Accessed April 17, 2025. https://www.mldsupportuk.org.uk/about-mld/ 14. Chang SC, Bergamasco A, Bonnin M, et al. A systematic review on the birth prevalence of metachromatic leukodystrophy. Orphanet J Rare Dis. 2024;19:80. 15. Soderholm HE, Chapin AB, Bayrak-Toydemir P, Bonkowsky JL. Elevated leukodystrophy incidence predicted from genomics databases. Pediat Neurol. 2020;111:66-69. 16. What is MLD? Cure MLD. Accessed April 17, 2025. https://www.curemld.com/what-is-mld