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Título

A complex association of sensorimotor axonal neuropathy, deafness, episodic worseness, and retinopathy: Mitchell syndrome

RESUMO

Case Presentation: A 28-year-old Brazilian woman presented with a long-standing clinical course of lower limb weakness starting at age 15 years, associated with recurrent and prolonged episodes of numbness and neuropathic pain. Her symptoms evolved and after five years she presented with worseness of motor symptoms and sensory loss in the lower limbs, mild motor compromise of the upper limbs, and bilateral sensorineural hearing loss. After almost one decade of symptom-onset, she noted marked worseness of motor symptoms, urinary disturbances, severe hearing loss (with the need of bilateral cochlear implants), and progressive unilateral visual loss of the left eye. Medical history disclosed short stature of unknown etiology. No parental consanguinity was observed. Examination disclosed distal dominant quadriparesis with brisk global reflexes and absent Achillean tendon reflexes, sensory ataxia, steppage gait, and marked hypoesthesia and hypopalesthesia in the lower limbs.
Neurophysiological studies disclosed axonal sensorimotor polyneuropathy. Brain MR imaging showed mild periventricular leukoencephalopathy. Optic coherence tomography showed bilateral thinning of the neurossensorial retina. As riboflavin transporter defect was suspected, oral riboflavina was started, 20 mg per kg, with moderate improvement of motor, visual and hearing complaints. NGS-based gene panel testing showed the heterozygous variant c.1384C>T (p.Arg462Cys) in the ACOX1 gene involved with Mitchell syndrome.

Discussion: Palmitoyl acyl-CoA oxidase 1 represents the rate-limiting peroxisomal enzyme involved in the beta-oxidation of fatty acids, which is related both to loss-of-function mechanisms with enzyme deficiency due to biallelic variants and to gain-of-function with neurotoxic mechanisms due to heterozygous variant. Mitchell syndrome is an extremely rare progressive inherited neurometabolic and neurodegenerative disorder associated with sensorimotor polyneuropathy, deafness, and episodes of clinical worseness with central or peripheral demyelination. Our case description disclosed progressive visual loss and moderate response to riboflavin therapy.

Final comments: Clinicians must be aware about the possibility of facing new clinical presentations of inherited peroxisomal disorders, such as Mitchell syndrome, in the clinical context of progressive hearing loss, polyneuropathy, sensory ataxia, visual loss, and acute or subacute episodes of motor and sensory worseness.

Palavras Chave

Mitchell syndrome, ACOX1, peroxisomal disorder