Category: Rare Genetic and Metabolic Diseases
Objective: To present a case of spastic paraparesis associated to a rare mitochondrial disorder.
Background: Metabolic disorders may have a clinical course overlapping common neurodegenerative movement disorders. Some red flags may prompt clinician to suspect inborn error of metabolism (IEM).
Results: A woman with neurodevelopmental delay since infancy, developed a subacute paraparesis at 2.5 years of age following an intercurrent infectious disease. Optic nerve atrophy was then additionally identified, and the patient was diagnosed with cerebral palsy associated with post-encephalitis status, despite progressive gait changes until she presented to our neurological department at 34 years of age. Besides short stature, she had no cognitive impairment. She had slow eye movements, saccade decomposition, dysarthria, proximal paraparesis, absence of lower limb (LL) osteotendinous reflexes, bilateral Babinski sign, abnormal proprioception and vibration in LL, paraparetic gait, hyperlordosis and small feet. Ocular fundi showed pale papilla. She had family history of Parkinson’s disease and visual impairment. Lab work showed normal vitamins (E, B12 and folic acid), iron metabolism, CK, lactate/pyruvate, AAs blood/urine, organic acids, hexosaminidase, galactocerebrosidase, ammonia and endocrinologic investigation. Brain MRI showed elevation of ferromagnetic deposits at basal ganglia, atrophy of pons, medial and superior cerebellar pedunculus and the body of the callosum commissure, and periventricular white matter changes. Spinal MRI was normal. NCS confirmed axonal polyneuropathy, with normal cutaneous and muscular biopsies. Mitochondrial DNA complete sequencing was negative. Neuroexome sequencing identified 2 variants in NFU1 gene: c.298G>C (p.Ala100Pro)(VUS) and c.622G>T (p.Gly208Cys)(known pathogenic), in trans, confirmed by segregation analysis. MRI spectroscopy identified changes supporting the diagnosis.
Conclusion: NFU1 mutations are associated with a Multiple Mitochondrial Dysfunction Syndrome, that may present as the fatal form type 1 or as a spastic paraparesis. Compound heterozygosity may be responsible for the milder phenotype, as in our patient. This case illustrates a rare metabolic disorder as phenocopy of neurodegenerative diseases. In the presence of an unexplainable movement disorder, the clinician should search for IEM that, in some cases, may uncover potentially treatable diseases.
To cite this abstract in AMA style:D. Silva, A. Travessa, R. Roque, L. Guedes. Slowly progressive spastic paraplegia due to rare mitochondrial dysfunction: a clinical case [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/slowly-progressive-spastic-paraplegia-due-to-rare-mitochondrial-dysfunction-a-clinical-case/. Accessed December 2, 2023.
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