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2024, Number 3

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Rev Mex Pediatr 2024; 91 (3)

Infantile form of metachromatic leukodystrophy with compound heterozygous variant in ARSA

Cabarcas-Castro L, Ramón-Gómez JL, Espinosa-García E, Suárez-Obando F, Santamaría-Castiblanco N, Martínez-Córdoba N, Lince-Rivera I

Language: Spanish
References: 22
Page: 105-109
PDF size: 388.85 Kb.


ABSTRACT

Introduction: metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by mutations in the arylsulfatase A (ARSA) gene. We present a case of MLD with a compound heterozygous variant in the ARSA gene that has rarely been associated with the infantile form of the disease. Case description: male patient, who at 14 months of age presented rapidly progressive developmental delay, characterized by motor and language regression, neurosensory hearing loss, generalized hyporeflexia, spasticity in the lower limbs, ataxia, dysmetria and dysphagia for liquids. ARSA enzymatic activity in leukocytes and plasma was decreased. Magnetic resonance imaging revealed symmetrical demyelination of the cerebral white matter. Nerve conduction studies showed demyelinating polyneuropathy in all four limbs. Genetic analysis revealed two probably pathogenic variants in the ARSA gene: the first nonsense type at c.643C>T p.Gln215* (inherited from the father) and the other missense at c.316G>A p.Glu106Lys (inherited from the mother), both associated with MLD. Conclusions: this case highlights the importance of genetic characterization in patients with MLD, in order to discover variants that had not been previously reported.


REFERENCES

  1. McAllister RG, Liu J, Woods MW, Tom SK, Rupar CA, Barr SD. Lentivector integration sites in ependymal cells from a model of metachromatic leukodystrophy: non-B DNA as a new factor influencing integration. Mol Ther Nucleic Acids. 2014; 3(8): e187. doi: 10.1038/mtna.2014.39.

  2. Van Rappard DF, Boelens JJ, Wolf NI. Metachromatic leukodystrophy: disease spectrum and approaches for treatment. Best Pract Res Clin Endocrinol Metab. 2015; 29(2): 261-273. doi: 10.1016/j.beem.2014.10.001.

  3. Wang BL, Lu FL, Sun YC, Wang HJ. Case report: a compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy. Front Neurol. 2022; 13: 1011019. doi: 10.3389/fneur.2022.1011019.

  4. Gieselmann V, Krageloh-Mann I. Metachromatic leukodystrophy-an update. Neuropediatrics. 2010; 41(1): 1-6. doi: 10.1055/s-0030-1253412.

  5. Madaan P, Jauhari P, Chakrabarty B, Kumar A, Gulati S. Saposin B-deficient metachromatic leukodystrophy mimicking acute flaccid paralysis. Neuropediatrics. 2019; 50(5): 318-321. doi: 10.1055/s-0039-1692646.

  6. Tomassy GS, Dershowitz LB, Arlotta P. Diversity matters: a revised guide to myelination. Trends Cell Biol. 2016; 26(2): 135-147. doi: 10.1016/j.tcb.2015.09.002.

  7. Stadelmann C, Timmler S, Barrantes-Freer A, Simons M. Myelin in the central nervous system: structure, function, and pathology. Physiol Rev. 2019; 99(3): 1381-1431. doi: 10.1152/physrev.00031.2018.

  8. Sarret C. Leukodystrophies and genetic leukoencephalopathies in children. Rev Neurol (Paris). 2020; 176(1-2): 10-19. doi: 10.1016/j.neurol.2019.04.003.

  9. Sheth J, Nair A, Jee B. Lysosomal storage disorders: from biology to the clinic with reference to India. Lancet Reg Health Southeast Asia. 2022; 9: 100108. doi: 10.1016/j.lansea.2022.100108.

  10. Ozgen H, Baron W, Hoekstra D, Kahya N. Oligodendroglial membrane dynamics in relation to myelin biogenesis. Cell Mol Life Sci. 2016; 73(17): 3291-3310. doi: 10.1007/s00018-016-2228-8.

  11. Sherman DL, Brophy PJ. Mechanisms of axon ensheathment and myelin growth. Nat Rev Neurosci. 2005; 6(9): 683-90. doi: 10.1038/nrn1743.

  12. Plotegher N, Duchen MR. Crosstalk between lysosomes and mitochondria in Parkinson's disease. Front Cell Dev Biol. 2017; 5: 312809. doi: 10.3389/fcell.2017.00110.

  13. Wong YC, Kim S, Peng W, Krainc D. Regulation and function of mitochondria-lysosome membrane contact sites in cellular homeostasis. Trends Cell Biol. 2019; 29(6): 500-513. doi: 10.1016/j.tcb.2019.02.004.

  14. Eichler FS, Cox TM, Crombez E, Dali CI, Kohlschutter A. Metachromatic leukodystrophy: an assessment of disease burden. J Child Neurol. 2016; 31(13): 1457-1463. doi: 10.1177/0883073816656401.

  15. Mahmood A, Berry J, Wenger DA, Escolar M, Sobeih M, Raymond G 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. doi: 10.1177/0883073809341669.

  16. Rauschka H, Colsch B, Baumann N, Wevers R, Schmidbauer M, Krammer M et al. Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype. Neurology. 2006; 67(5): 859-863. doi: 10.1212/01.wnl.0000234129.97727.4d.

  17. Hayashi T, Nakamura M, Ichiba M, Matsuda M, Kato M, Shiokawa N et al. Adult-type metachromatic leukodystrophy with compound heterozygous ARSA mutations: a case report and phenotypic comparison with a previously reported case. Psychiatry Clin Neurosci. 2011; 65(1): 105-108. doi: 10.1111/j.1440-1819.2010.02169.x.

  18. Penzien JM, Kappler J, Herschkowitz N, Schuknecht B, Leinekugel P, Propping P et al. Compound heterozygosity for metachromatic leukodystrophy and arylsulfatase A pseudodeficiency alleles is not associated with progressive neurological disease. Am J Hum Genet. 1993; 52(3): 557-564.

  19. Hohenschutz C, Eich P, Friedl W, Waheed A, Conzelmann E, Propping P. Pseudodeficiency of arylsulfatase A: a common genetic polymorphism with possible disease implications. Hum Genet. 1989; 82(1): 45-48. doi: 10.1007/BF00288270.

  20. Schiffmann R, van der Knaap MS. Invited article: an MRI-based approach to the diagnosis of white matter disorders. Neurology. 2009; 72(8): 750-759. doi: 10.1212/01.wnl.0000343049.00540.c8.

  21. Van Rappard DF, Bugiani M, Boelens JJ, van der Steeg AF, Daams F, de Meij TG et al. Gallbladder and the risk of polyps and carcinoma in metachromatic leukodystrophy. Neurology. 2016; 87(1): 103-111. doi: 10.1212/WNL.0000000000002811.

  22. Page KM, Stenger EO, Connelly JA, Shyr D, West T, Wood S et al. Hematopoietic stem cell transplantation to treat leukodystrophies: clinical practice guidelines from the Hunter's Hope Leukodystrophy Care Network. Biol Blood Marrow Transplant. 2019; 25(12): e363-e374. doi: 10.1016/j.bbmt.2019.09.003.




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