Objective: To present reported two siblings of PLAN representing complicated HSP.

Background: Neurodegeneration with brain iron accumulation (NBIA) is a group of diseases characterized by movement disorder and abnormal iron accumulation, particularly in the basal ganglia. PLA2G6-associated neurodegeneration (PLAN) is a subgroup of NBIA caused by PLA2G6mutations with autosomal recessive inherent. Clinically, there are 3 phenotypes were recognized including infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), and PLA2G6-related dystonia-parkinsonism.Hereditary spastic paraplegia (HSP) is another group of heterogeneous neurodegenerative disorders that is associated with progressive lower limb weakness and spasticity. “Complicated” HSP is associated with additional neurological abnormalities, such as cerebellar dysfunction, cognitive impairment, extrapyramidal symptoms, peripheral nerve or myopathy.

Method: A 39-year-old woman presented with chronic gait disorder since her age of 13. Besides, she also had urinary urgency with incontinence, and psychiatric disorder. Her younger brother had similar gait problem since early childhood and was diagnosed with spastic paraplegia. There were no other affected family members nor parental consanguinity and autosomal recessive (AR) HSP was diagnosed initially. However, she had newly onset slow movement, limbs and trunk stiffness and clumsiness and abnormal dystonic posture at about 36 years of age.The neurologic examination of this lady revealed masked face, bradykinesia, limb dystonia, spastic gait and generalized hyperreflexia except for hyporeflexic ankle jerks. Vibration and position sensation were also impaired over distal lower limbs.

Results: MRI of brain showed prominent cerebellar atrophy, vertical-oriented splenium of corpus callosum, shallow optic chiasma, but no iron accumulation. The 99m-Tc TRODAT-1 SPECT imaging revealed decreased tracer uptake in the bilateral striatum. The genetic study confirmed compound heterozygous missense mutation c.991G>T, p.Asp331Tyr and cryptic splice site mutation in intron 9/ exon 10 ofPLA2G6gene.

Conclusion: Our case study demonstrates a wide phenotypic spectrum and intra-familial variability of PLAN. A new phenotype of complicated HSP has been proposed recently. Screening of PLA2G6mutation in HSP patients with brain iron accumulation or other characteristic findings on MRI is therefore suggested.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-family-of-phospholipase-a2-associated-neurodegeneration-presented-as-complicated-hereditary-spastic-paraplegia/