The Autosomal recessive ataxias, their loci, genes, proteins, onset and distinguishing features2–4
| Autosomal recessive syndrome(s) (references) | Locus | Gene | Protein | Age at onset (years) | Distinguishing features |
|---|---|---|---|---|---|
| Friedreich’s ataxia 1 (FRDA1)/2 (FRDA2)5–7,40 | 9q13/9p23 | X25/ − | Frataxin/ − | 4–40 | Hyporeflexia, positive Babinski sign, deep sensory loss, cardiomyopathy, diabetes mellitus, scoliosis |
| Ataxia teleangiectasia (AT)/AT-like9,10 | 11q22–23/11q21 | ATM/hMRE11 | Phosphatidylinositol 3-kinase/hMRE11 protein | 0–20 | Teleangiectasia, immune deficiency, cancer, chromosomal instability, elevated AFP |
| Vitamin E deficiency (AVED)11 | 8q13 | α-TTP | α-Tocopherol transfer protein | 2–52 (<20) | As FRDA but rare cardiomyopathy and diabetes, head titubation |
| Abetalipoproteinaemia (ABL)12 | 4q22–24 | MPT | Microsomal triglyceride transfer protein | 2–52 | Steatorrhea, areflexia, retinitis pigmentosa, acanthocytosis, low cholesterol and β-lipoproteins |
| Spastic ataxia Charlevoix-Saguenay (ARSACS)13,14 | 13q12 | SACS | Sacsin | Childhood | Spasticity, polyneuropathy, striated retina, mitral valve prolapse |
| Infantile onset spinocerebellar ataxia (IOSCA)15 | 10q24 | – | – | ½–1½ | Ophthalmoplegia, hypotonia, hypacusis, athethosis, peripheral neuropathy |
| Ataxia with oculomotor apraxia 1 (AOA1)/2 (AOA2)16,17 | 9p13/9q34 | APTX/SETX | Aprataxin/senataxin | 2–18/10–22 | Oculomotor apraxia, chorea-athethosis, hypoalbuminaemia, sensory neuropathy, elevated AFP, CPK and cholesterol |
| Refsum’s disease (RD)18,19,41 | 10p11-pter, 6q22–24 | PHYH, PEX7 | Phytanoyl-CoA hydroxylase, peroxin 7 | Childhood | Retinitis pigmentosa, deafness, polyneuropathy, cardiomyopathy, elevated phytanic acid |
| Carbohydrate deficient glycoconjugate syndrome 1a (CDG 1a)20,21 | 16p13 | PMM2 | Phosphomannomutase 2 | Childhood | Hypotonia, mental retardation, failure to thrive, lipodystrophy, hepatic dysfunction, polyneuropathy, retinitis pigmentosa |
| Tay-Sachs disease (GM2 gangliosidosis)22,42 | 15q23–24 | HEXA | Hexosaminidase A | Child/adulthood | Mental retardation, cherry red spot, blindness, epilepsy, hypotonia, startle response, low hexosaminidase A |
| Krabbe43 | 14q31 | GALC | Galactosylceramidase | Child/adulthood | Mental retardation, polyneuropathy, optic atrophy, epilepsy, low galactocerebroside |
| Metachromatic leucodystrophy (MLD)44 | 22q13 | ARSA | Arylsulfatase A | Child/adulthood | Mental retardation, polyneuropathy, spasticitiy, optic atrophy, epilepsy, psychiatric symptoms, low arylsulfatase |
| Wilson’s disease45 | 13q14–21 | ATP7B | ATPase Cu transporting β polypeptide | 10–30 | Liver cirrhosis, Kayser-Fleischer rings, arthritis, nephrocalcinosis, high calcium, low ceruloplasmin, high copper |
| Cerebrotendinous xanthomatosis (CTX)46 | 2q33–ter | CYP27A1 | Cytochrome 450, subfamily27A1 | 10–20 | Cataract, premature atherosclerosis, spasticity, xanthoma, xanthelasmata, cholesterol and cholestanol elevated |
| Hartnup47 | 5p15 | – | – | Child/adulthood | Pellagra, emotional instability, aminoaciduria |
| Maple syrup urine disease (MSU)48 | 19q13 | BCKDHA | Branched chain keto acid dehydrogenase E1 alpha | Newborn/child | Feeding problems, epilepsy, mental retardation, hypoglycaemia, ketosis |
| Biotinidase deficiency49 | 3p25 | BTD | Biotinidase | 1–2 | Hypotonia, epilepsy, optic atrophy, hearing loss, skin rash, alopecia, ketoacidosis, organic aciduria |
| Carnitine acetyltransferase deficiency50 | 9q34 | CRAT | Carnitine acetyltransferase | Childhood | Hypotonia, mental disturbances, oculomotor palsy, failure to thrive |
| Gamma-glutamyl cysteine synthetase51 | 6p21 | GCLC | Gamma-glutamyl cysteine synthetase | Adult | Haemolytic anaemia, myopathy, polyneuropathy |
| L-2 Hydroxyglutaric acidaemia52 | – | – | – | Childhood | Mental retardation, short stature, leucodystrophy, macrocephaly |
| Niemann-Pick C53 | 18q11–12 | NPC1 | NPC1 protein | Child/adulthood | Epilepsy, spasticity, hepatosplenomegaly, dementia, psychiatric symptoms |
| Progressive myoclonus epilepsy (Baltic or Unverricht-Lundborg)23 | 21q22 | CSTB | Cystatin B | 6–13 | Epilepsy, myoclonus, mental deterioration |
| Marinesco-Sjogren syndrome24 | 5q31 | MSS | – | Childhood | Cataract, myopathy, hypotonia, short stature, microcephaly, mental retardation, hypergonadotropic hypogonadism |
| Posterior column ataxia with retinitis pigmentosa (PCARP)25 | 1q31–32 | AXPC1 | – | Childhood | Deep sensory loss, retinitis pigmentosa, areflexia |
| Boucher Neuhauser syndrome54 | – | – | – | 10–20 | Hypogonadotropic hypogonadism, chorioretinal dystrophy |
| Holmes syndrome26,27,55 | – | – | – | 10–30 | Hypogonadotropic/hypergonadotropic hypogonadism |
| Ataxia with neuronal migration defect56 | 16q12–22 | BFPP | – | Congenital | Bilateral frontoparietal polymicrogyria, mental retardation, epilepsy |
| Ataxia with deafness and mental retardation57 | – | – | – | Congenital | Deafness, mental retardation |
| Ataxia with saccadic intrusions58 | – | – | – | >30 | Saccadic intrusions, myoclonic jerks, spasticity, deep sensory loss, fasciculations, pes cavus |
| Ataxia with optic atrophy and deafness8 | 6p21–23 | – | – | Childhood | Deafness, optic atrophy |
| Leukoencephalopathy with vanishing white matter59 | 12/14q24/1//2p23/3q27 | EIF2B1, B2, B3 B4, B5 | Translocation initiation factor eIF2B 5 subunits | Child/adulthood | Leucodystrophy, ovarian failure, optic atrophy, motor deterioration, epilepsy |
| Ataxia with axonal neuropathy (SCAN1)60 | 14q31–32 | TDP1 | Tyrosyl-DNA phosphodiesterase 1 | Child/adulthood | Axonal polyneuropathy, pes cavus |
| Ataxia with laryngeal abductor paralysis and motor neuropathy61 | – | – | – | Adult | Dysphonia, motor neuropathy |
| Ataxia adult onset with thalamic lesions62 | – | – | – | >30 | Hyporeflexia, deep sensory loss, axonal polyneuropathy, mild cognitive impairment, bilateral thalamus lesions, |
| Xeroderma pigmentosum A–G63 | 9q22, 2q21, 3p25, 19q13, 11p11–12, 16p13, 13q32–33 | XPA, XPB, XPC, XPD, XPE, XPF, XPG | – | Child/adulthood | Defective DNA repair, skin atrophy, teleangiestasia, skin cancer, mental retardation |
| Nijmegen breakage syndrome64 | 8q21 | NBS1 | – | Childhood | Microcephaly, short stature, no mental retardation, immunodeficiency, cancer, chromosome instability |
| Cockayne syndrome a65 | 5 | CKN1 | – | Childhood | Retinitis pigmentosa, optic atrophy, short stature, presenile appearance, photosensitivity, deafness |
| Cerebelloparenchymal disorder II66 | – | – | – | >40 | Ataxia and dysarthria |
| Ataxic cerebral palsy67 | 9p12–q12 | – | – | Congenital | Non-progressive ataxic cerebral palsy |
| Joubert syndrome 1/268,69 | 9q34/11p12–q13 | JBTS1/CORS2 | –/– | Congenital | Vermis hypoplasia, mental retardation, hypotonia, episodic hyperpnea, retinal dystrophy, renal cysts |
| Behr syndrome70 | – | – | – | Childhood | Optic atrophy, mental retardation |
| Gillespie syndrome71 | – | – | – | Congenital | Aniridia, mental retardation |
| Chorea-acanthocytosis28 | 9q21 | CHAC | Chorein | 25–45 | Chorea, acanthocytes, epilepsy, peripheral neuropathy, myopathy, self-mutilation, basal ganglia atrophy |
| Cayman Island ataxia29 | 19p13 | ATCAY | Caytaxin | Childhood | Hypotonia, mental retardation, non-progressive ataxia |
| Cerebelloparenchymal disorder III8,30,37 | 9q34–ter | CLA1 | – | Congenital | Short stature, mental retardation |
| Ataxia, mental retardation, optic atrophy, skin abnormalities (CAMOS)31 | 15q24–26 | CAMOS | – | Congenital | Mental retardation, microcephaly, optic atrophy, short stature, abnormal osmiophilic pattern of skin vessels |
| Norwegian infantile onset ataxia32 | 20q11–13 | CLA3 | – | Congenital | No mental retardation, pes planus, short stature, spasticity, non-progressive ataxia |