Broadening the Horizons of Mitochondrial Parkinsonism
Year: 2025
Type: article
Study design: Case Report
Abstract: Sir, Spastic paraplegia 7 (SPG-7) is characterized by insidiously progressive spastic paraparesis with diminished vibration sense. Additional features including ataxia, spastic dysarthria, dysphagia, pale optic discs, nystagmus, strabismus, ptosis, hearing loss, neuropathy, amyotrophy, skeletal abnormalities, and urinary disturbances may also be seen. However, literature has also shown the presence of Parkinsonism. Our case manifested as pure Parkinsonian syndrome disguising the actual pathology. A 45-year-old female, born to non-consanguineous parents, a homemaker, came to us with a slowness of activities of daily living for 1 year followed by right-hand tremor and change of speech. She never sustained any fall. There was no history of heavy metal or farming exposure with non-contributory family history. She exhibited hypomimia with hypophonic speech. Her mini-mental status examination score (MMSE) was 28. Eye testing showed broken pursuits and slow saccades only. She had bilateral upper limb (UL) rigidity and bradykinesia, right more than left associated with similar symptoms in the right lower limb (LL). Rest and postural tremor was noted in the right UL and LL. Her motor unified Parkinson’s disease rating scale score (UPDRS) was 34 with Hoehn and Yahr (H and Y) stage two. She had no non-motor symptoms. So, a diagnosis of early Parkinson’s disease was made and levodopa carbidopa along with trihexyphenidyl (THP) was started with gradual uptitration. After 1 month of levodopa equivalent dose (LED) of 300 mg and THP of 8 mg, her motor score reduced to 15 from 28. Her blood work and magnetic resonance imaging (MRI) brain came out normal. Her L-6-[18F] fluoro-3,4-dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) scan showed slightly reduced presynaptic dopaminergic uptake in left putamen depicting presynaptic dopaminergic uptake deficit. Genetic testing revealed compound heterozygous variants in the SPG-7 gene: p.Ala510Val, p.Leu78Ter. This missense c.1529C>T (p.Ala510Val) variant in SPG-7 gene has been reported in individuals affected with autosomal recessive SPG but has shown dominant effect in some cases also.[1] SPG-7 is caused by homozygous or compound heterozygous mutation in the paraplegin gene (SPG-7) on chromosome 16q24. This gene encodes paraplegin, which is required for the maintenance of mitochondrial deoxyribonucleic acid (DNA) proteins, so it is postulated that its mutation will lead to mitochondrial dysfunction.[2] In the largest series of patients with SPG-7, the overall clinical phenotype is characterized by slowly progressive spastic paraparesis, variable degrees of cerebellar ataxia, ophthalmoplegia, and optic atrophy contrary to our patient who had only Parkinsonism.[3] SPG type 7 is one of the most common subtypes of autosomal recessive hereditary SPGs, manifesting predominantly in adulthood. Our patient had a compound heterozygous mutation but still manifested with an unusual phenotype mimicking idiopathic Parkinson’s disease. She also had a significant reduction of UPDRS motor score after levodopa. Table 1 describes cases showing levodopa-responsive symmetric Parkinsonism unlike our case with asymmetrical Parkinsonism.Table 1: Other studies showing Parkinsonism associated with other clinical features with SPG-7 gene mutationDeclaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Neurology India
Authors: Mridula Singh, Deepti Grover, Suman Kushwaha
Institution: Institute of Human Behaviour and Allied Sciences
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4409498280