Case report: metachromatic leukodystrophy, its clinical evolution and diagnostic management

Case presentation: We report a case of a female infant, with a normal previous neuropsychomotor development, at 21 months of age had presented a sudden regression of development after an infectious condition. Initially its courses were composed by ataxia, vomiting, hypotonia and behavior alteration, loss of gait and language in a period of two months, associated with focal seizures, relevant dystonia (opisthotonus) and spasticity. Levetiracetam, baclofen and clobazam were prescribed, with seizure control and partial control of spasticity and dystonia. The initial investigation was directed to inborn errors of metabolism, revealing metabolic acidosis, elevated lactorrachia, proteinorrachia and increased serum creatine phosphokinase, and abnormal amino acid chromatography. Cranial magnetic resonance imaging evidenced signs of intense demyelination, with diffuse and symmetrical T2 hypersignal, affecting mainly the periventricular region and the left cerebellar hemisphere. At first, the diagnostic hypothesis of mitochondrial disease was raised, which was excluded after the genetic panel (ARSA-intron2- c.465+1G>A), which is associated with metachromatic leukodystrophy.

Discussion: Metachromatic leukodystrophy has an estimated worldwide prevalence of 1/40,000–160,000. It is a lysosomal storage disease, of autosomal recessive inheritance, characterized by the demyelination of the central and peripheral nervous systems, associated with clinical developmental regression syndrome. The late infantile form has an incidence of 50–60% of cases and presents with a developmental regression syndrome up to thirty months of age, which is more severe, due to rapid neurodegenerative progression, and the diagnosis is confirmed by genetic testing or arylsulfatase dosage. To date, supportive therapeutic strategies are: warfarin, simvastatin, prednisolone, and immunoglobulin to reduce neuroinflammation, in addition to baclofen and anticonvulsants. Stem cell transplantation, enzyme replacement therapy and viral vectors are currently being studied.

Final comments: The case refers to the late infantile form, without correlating genotype-phenotype with the course of the disease. Laboratory findings are consequences of lysosomal system dysfunction, which secondarily alters other organs, and radiological findings with a demyelinating pattern. These results are similar to the leukodystrophies group, and genetic testing concludes the diagnosis. In the presence of clinical worsening, supportive therapeutic measures will be reassessed.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023