Table 3.

Autosomal recessive ataxias: Molecular genetics and clinical phenotype

Disorder	Gene product	Function
Mitochondrial/Oxidative stress
Friedreich ataxia (FRDA)	frataxin	synthesis of rion sulphur clusters
Mitochondrial recessive ataxia syndrome (MIRAS)	polymerase gamma (POLG)	mitochondrial DNA proofreading
Infantile onset spinocerebellar ataxia (IOSCA)	twinkle	mitochondrial DNA proofreading
Autosomal recessive cerebellar ataxia type 2 (ARCA2, SCAR9)	ADCK3	coenzyme Q10 synthesis
Ataxia with isolated vitamin E deficiency (AVED)	α-tocopherol transport protein	vitamine E
Abetalipoproteinemia	microsomal triglyceride transfer protein	vitamine E
DNA repair
Ataxia telangiectasia (AT)	ATM protein	phosphoinositol-3 kinase activity: cell cycle checkpoint control and DNA repair
Ataxia telangiectasia-like disorder (ATLD)	MRE11	double strand DNA repair
Ataxia with oculomotor apraxia type 1 (AOA1)	aprataxin	single strand DNA repair
Ataxia with oculomotor apraxia type 2 (AOA2, SCAR2)	senataxin	single strand DNA repair
Spinocerebellar ataxia with axonal neuropathy 1 (SCAN1)	tyrosyl-DNA phosphodi-esterase- 1 (TDP1)	DNA replication
Other mechanisms
Refsum disease	phytanoyl-CoA hydroxylase	oxidation of phytanic acid
Cerebrotendinous xanthomatosis (CTX)	sterol-27 hydroxylase	sterol hydroxylation
ARSACS	sacsin	proteasomal system
Marinesco-Sjögren syndrome (MSS)	SIL1	ER glycoprotein
Autosomal recessive cerebellar ataxia type 1 (ARCA1, SCAR8)	SYNE1	Member of spectrin family
Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC)	ABHD12	endocannabinoid metabolism: hydrolysis 2-arachidonoyl glycerol (2-AG)