Objective: To describe three cases of complicated hereditary spastic paraplegia (cHSP) like presentation in PLA2G6.

Background: PLA2G6-associated neurodegeneration (PLAN) is a complex group of neurodegenerative diseases resulting from mutations in PLA2G6 gene. Typically, PLA2G6 related mutations present as infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, adult-onset dystonia-parkinsonism and autosomal recessive early-onset parkinsonism. A cHSP like presentation has been seldom described.

Method: A chart review.

Results: Case 1: 26-year-old lady presented with chronic progressive walking difficulty since the age of 16 years followed by memory impairment and pseudobulbar affect. On examination she had spastic ataxia with upgaze impairment. Neuroimaging showed basal ganglia mineralization with cerebellar atrophy.
Case 2: Brother of case 1, 32-year-old, presented with chronic progressive walking difficulty since the age of 20 years followed by pseudobulbar affect. On examination he had upgaze impairment, and spastic ataxia with pseudobulbar affect. Neuroimaging showed basal ganglia mineralization with cerebellar atrophy.
Case 3: 23-year-old gentleman presented with walking difficulty since the age of 18 years, followed by recurrent falls and action tremor of bilateral upper limbs with dysarthria and dysphagia. On examination he had spastic ataxia, bilateral mild upper limb dystonia, and multifocal myoclonus. Neuroimaging showed basal ganglia mineralization with frontal and cerebellar atrophy.
Based on the neuroimaging features a probable diagnosis of neurodegeneration with brain iron accumulation was considered in all three cases. Clinical exome next generation sequencing was performed to confirm the diagnosis. A homozygous c.2222G>A mutation in PLA2G6 resulting in a p.R741Q transition was observed in all three patients.

Conclusion: PLA2G6 mutations should be considered in patients who present with symptoms suggestive of cHSP with neuroimaging suggestive of basal ganglia mineralization and cerebellar atrophy.

References: Kishin Koh, Yuta Ichinose, Hiroyuki Ishiura et al. PLA2G6-associated Neurodegeneration Presenting as a Complicated Form of Hereditary Spastic Paraplegia. J Hum Genet, 2019;64,55-59.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/complicated-hereditary-spastic-paraplegia-like-presentation-of-homozygous-c-2222ga-mutation-in-pla2g6/