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The life expectancy for metachromatic leukodystrophy (MLD) is tragically short, so it’s important to recognize the signs and symptoms to diagnose and treat urgently1,2

The life expectancy for metachromatic leukodystrophy (MLD) is tragically short, so it’s important to recognize the signs and symptoms to diagnose and treat urgently1,2

Patients with MLD can appear healthy at birth, so look closely and act quickly3

Symptoms can be difficult to identify, and the disease progresses rapidly, so be vigilant of the early signs of MLD.4 Each MLD subtype (late infantile, early and late juvenile, and adult) has specific symptoms and rates of progression; however, all forms are progressive and fatal if left untreated.4,5

Over half of the children affected by MLD show symptoms in the first 3 years of life.5

Below are initial signs and symptoms for each subtype of MLD. Be on the lookout and pursue confirmatory laboratory testing if MLD is suspected.

Most children with late infantile MLD, the most aggressive form, die within 5 years of disease onset13
Most children with late infantile MLD, the most aggressive form, die within 5 years of disease onset13

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Hear one mother’s journey to an accurate MLD diagnosis

For more information download our Disease Awareness Brochure

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

How rare is MLD and who does it affect?

1 in 100 people are carriers of the ARSA mutation that can cause MLD.17

ARSA, arylsulfatase A.

MLD rapidly progresses, increasing the urgency for early diagnosis7,18

MLD is first suspected by recognizing the characteristic pattern of progressive impairment.19

Newborn screening is critical in ensuring that newborns are diagnosed and treated effectively before they become symptomatic and progression begins.6 If there is any suspicion of MLD based on suggestive clinical symptoms, refer to a specialist for confirmatory lab testing to rule out MLD.7

Biochemical testing can reveal the presence of MLD; genetic testing can confirm the diagnosis.7

Biochemical tests include urine sulfatide testing and ARSA enzyme activity testing.7 Genetic tests include gene sequencing for the ARSA gene variant.7

Magnetic resonance imaging (MRI) can also confirm a diagnosis of MLD, because it can show the presence and absence of myelin.19

MLD is rare, progressive, and fatal if left untreated. When diagnosed, there isn’t a moment to lose4

Refer your patient to a specialized treatment center familiar with the treatment of MLD

MLD is rare, progressive, and fatal if left untreated. When diagnosed, there isn’t a moment to lose4

Refer your patient to a specialized treatment center familiar with the treatment of MLD

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Hear one mother’s initial reactions to her daughter’s MLD diagnosis
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References 1. 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. 2. Fumagalli F, Calbi V, Natali Sora MG, et al. Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access. Lancet. 2022;399:372-383. 3. Gieselmann V, Krägeloh-Mann I. Metachromatic leukodystrophy – an update. Neuropediatrics. 2010;41:1-6. 4. 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. 5. Metachromatic leukodystrophy. National Organization for Rare Disorders. Accessed June 13, 2024. https://rarediseases.org/rare-diseases/metachromatic-leukodystrophy/#symptoms 6. Fumagalli F, Zambon AA, Rancoita PMV, et al. Metachromatic leukodystrophy: a single-center longitudinal study of 45 patients. J Inherit Metab Dis. 2021;44:1151-1164. 7. Wang RY, Bodamer OA, Watson MS, et al. Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. Gen Med. 2011;13:457-484. 8. 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 July 10, 2024. https://www.ncbi.nlm.nih.gov/books/NBK1130/ 9. von Figura K, Gieselmann V, Jaeken J. Metachromatic leukodystrophy. In: The Metabolic and Molecular Bases of Inherited Disease, Volume 3. 8th ed. McGraw Hill, 2001:3695-3724. 10. 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. 11. Fumagalli F, Zambon AA, Rancoita PMV, et al. Metachromatic leukodystrophy: a single-center longitudinal study of 45 patients. J Inherit Metab Dis. 2021;44:1151-1164. 12. Harrington M, Whalley D, Twiss J, et al. Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers. Orphanet J Rare Dis. 2019;14:89. 13. Metachromatic leukodystrophy. National Institute of Neurological Disorders and Stroke. Accessed July 10, 2024. https://www.ninds.nih.gov/health-information/disorders/metachromatic-leukodystrophy?search-term=MLD 14. About MLD. MLD Support Association UK. Accessed May 13, 2024. https://www.mldsupportuk.org.uk/about-mld/ 15. 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. 16. Soderholm HE, Chapin AB, Bayrak-Toydemir P, Bonkowsky JL. Elevated leukodystrophy incidence predicted from genomics databases. Pediat Neurol. 2020;111:66-69. 17. What is MLD? Cure MLD. Accessed June 13, 2024. https://www.curemld.com/what-is-mld 18. Chang SC, Eichinger CS, Field P. The natural history and burden of illness of metachromatic leukodystrophy: a systematic literature review. Eur J Med Res. 2024;29:181. 19. Metachromatic leukodystrophy. National Institute for Rare Disorders. Accessed July 10, 2024. https://rarediseases.org/rare-diseases/metachromatic-leukodystrophy/#diagnosis