Objective: We describe an interesting case of a young adult with a 5 year progressive history of spastic quadripareisis , cognitive decline, seizures and pseudobulbar affec

Background: The Hereditary Spastic Paraparesis (HSP) encompass a large group of disorders that classically presents with lower limb spasticity, urinary difficulty, and lower limb paresthesia. These disorders are seen in almost all inheritance patterns and till date have been reported in more than 80 genetic loci.The prevalence of these disorders worldwide is almost 0.1-9.6 instances in every 1,00,000 patients. Complicated HSP comprise a spectrum of manifestations including seizures, cognitive decline and extrapyramidal features which often pose a diagnostic challenge.

Method: Case report

Results: A 30 year old male born out of a non-consanguineous marriage with a normal birth and development, presented to us with spastic quadriparesis, spastic dysarthria, gait freezing and initiation difficulty, cognitive decline and pseudobulbar affect for about 5 years. The initial event was triggered by fever thus prompting a diagnosis of post encephalitic sequalae. However progression of motor disability, worsening of cognition and a family history of seizures and subsequent death in the younger sibling prompted us to search for a possible genetic association .He had a MMSE of 20,FAB 10 with poor attention span ,dysexecutive features along with hypertonia ,brisk reflexes, and spastic gait. After ruling out all possibilities ,a whole exome sequence was sent which showed ( VUS) mutation in KIF 1 A gene chromosome coordinate: exon 2 : 38 ,variant c.3928g>ap.asp1310asn.

Conclusion: One of SPG genes is KIF1A (Kinesin Family1A) ,a neuron-specific motor protein involved in intracellular axonal transport of vesicles along microtubules that contribute to pre- and post-synaptic assembly, autophagic processes and neuron survival. HSP-related kinesin-3 mutants are characterized by deficits in motility, regulation, and cargo binding.[1](SPG30) is characterized by slowly progressive spastic paraplegia in the first or second decades of life. Some patients have a form of the disorder, limited to spastic paraplegia, whereas others may have a complicated form[2]

References: 1.Gabrych DR, Lau VZ, Niwa S, Silverman MA. Going too far is the same as falling short: kinesin-3 family members in hereditary spastic paraplegia. Front Cell Neurosci. 2019;13:419.
2.Pennings M, Schouten MI, van Gaalen J, Meijer RPP, de Bot ST, Kriek M, Saris CGJ, van den Berg LH, van Es MA, Zuidgeest DMH, Elting MW, van de Kamp JM, van Spaendonck-Zwarts KY, Die-Smulders C, Brilstra EH, Verschuuren CC, de Vries BBA, Bruijn J, Sofou K, Duijkers FA, Jaeger B, Schieving JH, van de Warrenburg BP, Kamsteeg EJ. KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia. Eur J Hum Genet. 2020 Jan;28(1):40-49.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/expanding-the-spectrum-of-hereditary-spastic-paraplegia-an-interesting-case/