Category: Choreas (Non-Huntington's Disease)
Objective: Here we want to present a patient with chorea as part of clinical manifestation of adult onset of metachromatic leukodystrophy.
Background: Metachromatic leukodystrophy is a rare lysosomal disorder with autosomal recessive mutation in ARSA gene which leads to low arylsulfatase level and lipids build up in neurons and myelin. The adult form is less common and may begin with behavior and psychiatric problems, cognitive decline, ataxia, neuropathy and spastic paraparesis. As for our knowledge chorea was not report before in the liteature.
Method: Neurological examination was performed with nerve conduction studies and MRI of the brain. Arylsulfatase deficiency in leukocytes was determined by spectrophotometric analysis. Genetic mutation in ARSA gene was identified with next generation sequencing and confirmation of detected ARSA gene variants was done by Sanger sequencing after PCR amplification of target region.
Results: First symptoms in the form of behavioral changes started when the patient was 28 years old. Six years later involuntary movements of the head and limbs appeared which was categorized within neurological examination as chorea. In addition, the patient had cerebellar ataxia, voice and hand tremor, motor impersistence with dysexecutive syndrome. MRI of the brain showed periventricular more frontal changes in the white matter as T2/FLAIR hyperintensities with global atrophy. Nerve conduction studies showed symmetrical demyelinating sensorimotor polyneuropathy. Analysis of arylsulfatase activity was mildly below reference range 3.2nmol/h/mL. Genetic analysis of the ARSA gene revealed compound heterozygous pathogenic mutation in exon 3 p.Ile181Ser (c.542T>G, NM_001085425.3) and exon 4 p.Glu255Lys (c.763G>A, NM_001085425.3).
Conclusion: In patients with adult-onset of chorea, metachromatic leukodystrophy should be consider as for the differential diagnosis.
To cite this abstract in AMA style:
NT. Dragašević Mišković, A. Milovanović, M. Branković, I. Novaković, I. Petrović, A. Tomić Pešić, M. Svetel, VS. Kostić. Chorea as a clinical manifestation in adult-onset of metachromatic leukodystrophy [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/chorea-as-a-clinical-manifestation-in-adult-onset-of-metachromatic-leukodystrophy/. Accessed June 15, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/chorea-as-a-clinical-manifestation-in-adult-onset-of-metachromatic-leukodystrophy/