Table 4.

Subtypes of neurodegeneration with brain iron accumulation

Disease	Synonyms	Gene	Locus	Inheritance	MRI finding	Iron accumulation	Neuropathology
Pantothenate kinase-associated neurodegeneration (PKAN)	NBIA1	PANK2	20p13	AR	“Eye-of-the-tiger”	GP >SN	NFTs, spheroids.
PLA2G6-associated neurodegeneration (PLAN)	NBIA2, PARK14	PLA2G6	22q13.1	AR	Cerebellar atrophy	GP >SN	Lewy bodies, NFTs, spheroids
Mitochondrial membrane protein-associated neurodegeneration (MPAN)	NBIA4, SPG43	C19orf12	19q12	AR	T2 hyperintensity of medial medullary lamina	GP, SN	Lewy bodies, spheroids, tau
Beta-propeller protein-associated neurodegeneration (BPAN)	NBIA5, SENDA	WRD45	Xp11.23	XLD	T1 hyperintensity with central hypointensity in SN	SN >GP	Lewy bodies, NFTs, spheroids
COASY protein-associated neurodegeneration (CoPAN)	NBIA6	COASY	17q21.2	AR	GP calcification in one case (can mimic the “eye-of-the-tiger”)	GP, SN	N/A
Fatty acid hydroxylase-associated neurodegeneration (FAHN)	SPG35	FA2H	16q23	AR	Pontocerebellar atrophy. White matter changes. Thin CC	GP, SN	N/A
Kufor-Rakeb syndrome	PARK9, CLN12	ATP13A2	1p36.13	AR	Cerebral, cerebellar and brainstem atrophy	CN, P	Lipofuscin?
Woodhouse-Sakati syndrome	–	DCAF17	2q31.1	AR	White matter changes	GP, SN	N/A
Neuroferritinopathy	NBIA3	FTL	19q13.33	AD	Cystic cavitation in basal ganglia	P, CN, GP, Th, DN	Distorted, iron-laden nuclei
Aceruloplasminemia	–	CP	3q25.1	AR	Cerebellar atrophy. White matter changes	P, CN, GP, Th, DN	Bizarre astrocytes; glomerular structures
Adapted from Kruer [129], Gregory and Hayflick [130], Venco et al. [131] and Wiethoff et al. [132].

AR, autosomal recessive; AD, autosomal dominant; CC, corpus callosum; CN, caudate nucleus; DN, dentate nucleus; GP, globus pallidus; N/A, not available; NFT, neurofibrillary tangles; P, putamen; SN, substantia nigra; Th, thalamus; XLD, X-linked dominant.