Phospholipase A2-associated neurodegeneration (PLAN), a syndrome of Neurodegeneration with Brain Iron Accumulation (NBIA), is an autosomal recessive disorder caused by mutations in PLA2G6 gene.
The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome.
Mutations in 10 genes have been associated with NBIA that include Ceruloplasmin (Cp) and ferritin light chain (FTL), both directly involved in iron homeostasis, as well as Pantothenate Kinase 2 (PANK2), Phospholipase A2 group 6 (PLA2G6), Fatty acid hydroxylase 2 (FA2H), Coenzyme A synthase (COASY), C19orf12, WDR45 and DCAF17 (C2orf37).
Phospholipase A2 associated neurodegeneration (PLAN) is a major phenotype of autosomal recessive Neurodegeneration with Brain Iron Accumulation (NBIA).
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.
Neurodegeneration with brain iron accumulation (NBIA) involves several genetic disorders, two of which, aceruloplasminemia and neuroferritinopathy, are caused by mutations in genes directly involved in iron metabolic pathway, and others, such as pantothenate-kinase 2, phospholipase-A2 and fatty acid 2-hydroxylase associated neurodegeneration, are caused by mutations in genes coding for proteins involved in phospholipid metabolism.
A number of autosomal recessive NBIA syndromes can present in childhood, most commonly pantothenate kinase-associated neurodegeneration (PKAN; due to mutations in the PANK2 gene) and phospholipase A2 group 6-associated neurodegeneration (PLAN; associated with genetic defects in PLA2G6).