Objective: To report a case of a 32-year-old woman with progressive spastic paraparesis who was misdiagnosed initially as adult onset metachromatic leukodystrophy (MLD)

Background: MLD is an autosomal recessive lysosomal storage disorder caused by the deficiency of arylsulfatase A (ARSA). In adult form, the initial symptoms are often manifested psychiatric symptoms and behavioral abnormalities followed by motor signs, such as spastic paraplegia, cerebellar ataxia. An important tool in establishing the diagnosis of MLD is brain magnetic resonance imaging (MRI), which shows a bilateral symmetric periventricular white matter changes predominantly in the frontal regions.

Method: A 32-year-old woman presented with 3-year history of progressive gait disturbance and unsteadiness during walking. She was diagnosed with schizophrenia in psychiatry a few months ago. Since the age of 16, her gait gradually became worse and barely walked with help. Even then, she didn’t complain of cognitive impairment, but memory problem was worsened slowly. She had emotional change frequently and very labile affect recently. She showed wide-based and spastic gait with weakness of distal lower limbs. She presented parkinsonism such as hypomimia, bradykinesia, dysarthria and dysmetria of upper limbs.

Results: Thyroid function test, RPR, anti-HIV, cupper, ceruloplasmin, vitamin E, B1, B12 were normal. CSF profiles were in normal range and whole spine MRI, somatosensory evoked potential (SEP) were normal. Brain MRI showed bilateral, symmetrical increased T2 signal intensity in the post periventricular and deep white matter and thinning of anterior corpus callosum in sagittal T2 weighted image. Additionally, ARSA activity was checked twice and observed lower normal range, 0.54, 0.58 (nmol/min/mg, reference range 0.50~2.00). Whole exome sequencing (WES) and later Sanger study among her family was done. The homozygote splicing region (c.5866+1G>A) in chromosome 15 was detected. This patient was initially thought as adult MLD because of definite psychiatric symptoms, white matter lesion of brain MRI and low range of ARSA activity, but finally confirmed as spastic paraplegia 11 in WES.

Conclusion: When the clinician diagnoses rare disease, history takings and clinical diagnosis based on phenomenology are very important. But if test results were not compatible to diagnosis, genetic approaches might be one of possible tool.

References: Gieselmann V, Krageloh-Mann I. Metachromatic leukodystrophy – an update. Neuropediatrics 2010;41(1):1-6. Leite CC, Lucato LT, Santos GT, Kok F, Brandao AR, Castillo M. Imaging of adult leukodystrophies. Arq Neuropsiquiatr 2014;72(8):625-32. Stevanin G, Durr A, Brice A. Spastic Paraplegia 11. GeneReviewsⓡ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/hereditary-spastic-paraplegia-11-is-easy-to-be-misdiagnosed-as-adult-metachromatic-leukodystrophy/