In the PLA2G6 knockout (KO) mouse, which is an excellent PLAN model, specific membrane degeneration takes place in neurons and their axons, and this is followed by axonal spheroid formation.
We report a 13-month-old girl with infantile neuroaxonal dystrophy harboring a compound heterozygous mutation in the PLA2G6 gene with downbeat nystagmus as the only presenting symptom.
Mutations in the PLA2G6 gene are causative of PLA2G6-associated neurodegeneration (PLAN), a spectrum of neurodegenerative conditions including infantile, childhood and adult onset forms.
We describe the clinical phenotypes, neuroimaging features and PLA2G6 mutations in 5 children, of whom 4 presented with infantile neuroaxonal dystrophy (INAD).
PLA2G6-associated neurodegeneration (PLAN): further expansion of the clinical, radiological and mutation spectrum associated with infantile and atypical childhood-onset disease.
Pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2) are the core syndromes, but several other genetic causes have been identified (including FA2H, C19orf12, ATP13A2, CP and FTL).
Recently, it was reported that mutations in the PLA2G6 gene cause INAD, but neuropathological analysis of genetically confirmed individuals with neuroaxonal dystrophy has been limited.
Mutations in the phospholipase A2 Group 6 (PLA2G6) gene have been identified in autosomal recessive neurodegenerative diseases classified as infantile neuroaxonal dystrophy and neurodegeneration with brain iron accumulation.
Mutations in PLA2G6 gene have variable phenotypic outcome including infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, idiopathic neurodegeneration with brain iron accumulation and Karak syndrome.
The 2 major types of neurodegeneration with brain iron accumulation (NBIA) are the pantothenate kinase type 2 (PANK2)-associated neurodegeneration (PKAN) and NBIA2 or infantile neuroaxonal dystrophy (INAD) due to mutations in the phospholipase A2, group VI (PLA2G6) gene.
About 85% of INAD patients carry mutations in the PLA2G6 gene that encodes for a Ca(2+)-independent phospholipase A(2) (VIA iPLA(2)), but how these mutations lead to disease is unknown.
About 85% of INAD patients carry mutations in the PLA2G6 gene that encodes for a Ca(2+)-independent phospholipase A(2) (VIA iPLA(2)), but how these mutations lead to disease is unknown.
In addition to the core syndromes of pantothenate kinsase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2), several other genetic causes have been identified.