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Título

A potentially treatable Hereditary Spastic Paraplegia mimicker: spinal Cerebrotendinous Xanthomatosis

RESUMO

Case Presentation: A 23-year-old Brazilian man presented with a slowly progressive history of unsteady gait, lower limb stiffness and numbness involving both feet since 15 years old. Parents were both first degree cousins (consanguineous parents). Examination disclosed global brisk tendon reflexes, extensor plantar responses, moderate spastic paraparesis, and mild reduction in vibratory sense in the lower limbs. Mignarri score: 100.
General lab and biochemical screening were unremarkable. Nerve conduction studies showed demyelinating and axonal sensorimotor polyneuropathy. Needle electromyography studies remained unremarkable. Neuroimaging studies disclosed mild cervical spine atrophy, marked signal changes involving the dorsal column and lateral corticospinal tracts of the cervical and thoracic spinal cord. Gene panel testing including Hereditary Spastic Paraplegia (HSP) and Charcot-Marie-Tooth disease genes disclosed the pathogenic variant c.1183C>T (p.Arg395Cys) in homozygosis in CYP27A1 gene, defining the genetic diagnosis of Cerebrotendinous Xanthomatosis (CTX). Plasma cholestanol levels were assessed and showed increased levels. Serum cholesterol and triglyceride levels were normal. Ophthalmologic evaluation was normal. Patient was started on statins (simvastatin). Chenodeoxycholic acid was not available.
Discussion: CTX is a rare autosomal recessive inherited metabolic disorder due to pathogenic variants in the CYP27A1 gene. Typical systemic and neuroradiological findings represent important clinical clues for high suspicion in different neurological contexts. CTX presents with different neurological phenotypes, including spastic paraparesis (spinal CTX), lower motor neuron disease, cerebellar ataxia, dystonia, parkinsonism, epilepsy, and polyneuropathy. Spinal CTX has been reported in association with other common systemic signs, including chronic diarrhea, juvenile cataracts, and osteopenia.
However, pure neurological presentations without early systemic signs may also occur, representing a complex diagnostic challenge, mainly in contexts with broad differential diagnosis. Spinal CTX is commonly a late diagnosis. Mignarri index for CTX suspicion must not limit diagnostic evaluation in patients with pure neurological presentation, as early CTX treatment changes disease natural history. Final comments: Spinal CTX must be included in the differential diagnosis of HSP phenotypes, even in cases without marked multisystem involvement.

Palavras Chave

spastic paraparesis; Cerebrotendinous Xanthomatosis

Área

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