Autosomal recessive cerebellar ataxia with late-onset spasticity

MedGen UID:: 1635411
•Concept ID:: C4706412
•: Disease or Syndrome

Synonyms:	Autosomal recessive cerebellar ataxia due to GBA2 (glucosylceramidase beta 2) deficiency; Autosomal recessive cerebellar ataxia due to GBA2 deficiency; autosomal recessive cerebellar ataxia due to GBA2 deficiency; autosomal recessive cerebellar ataxia with late-onset spasticity
SNOMED CT:	Autosomal recessive cerebellar ataxia due to GBA2 (glucosylceramidase beta 2) deficiency (763348005); Autosomal recessive cerebellar ataxia with late-onset spasticity (763348005)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Monarch Initiative:	MONDO:0018129
Orphanet:	ORPHA352641

Definition

A rare genetic neurodegenerative disease with childhood or adolescent-onset of cerebellar ataxia with dysarthria which slowly progresses and associates pyramidal signs, including lower limb spasticity, brisk reflexes, and Babinski and Hoffman signs. Patients typically present cerebellar ataxia with development of increasing asymmetric spasticity in upper and lower limbs, and variable axonal sensory or sensorimotor neuropathy. Additional heterogeneous features, including pes cavus, scoliosis and abnormalities of the brain (e.g. cerebral atrophy) may also be associated. [from SNOMEDCT_US]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVAutosomal recessive cerebellar ataxia with late-onset spasticity

Autosomal recessive metabolic cerebellar ataxia
- Autosomal recessive cerebellar ataxia with late-onset spasticity

Recent clinical studies

Etiology

AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients.

Colucci F, Neri M, Fortunato F, Ferlini A, Carrozzo R, Torraco A, Lamantea E, Legati A, Tecilla G, Pugliatti M, Sensi M
Cerebellum 2023 Dec;22(6):1313-1319. Epub 2022 Nov 30 doi: 10.1007/s12311-022-01497-y. PMID: 36447112

Prevalence and phenotype of the c.1529C>T SPG7 variant in adult-onset cerebellar ataxia in Italy.

Mancini C, Giorgio E, Rubegni A, Pradotto L, Bagnoli S, Rubino E, Prontera P, Cavalieri S, Di Gregorio E, Ferrero M, Pozzi E, Riberi E, Ferrero P, Nigro P, Mauro A, Zibetti M, Tessa A, Barghigiani M, Antenora A, Sirchia F, Piacentini S, Silvestri G, De Michele G, Filla A, Orsi L, Santorelli FM, Brusco A
Eur J Neurol 2019 Jan;26(1):80-86. Epub 2018 Sep 3 doi: 10.1111/ene.13768. PMID: 30098094

Peripheral nerve involvement in hereditary cerebellar and multisystem degenerative disorders.

Berciano J, García A, Infante J
Handb Clin Neurol 2013;115:907-32. doi: 10.1016/B978-0-444-52902-2.00051-5. PMID: 23931821

Mutations in SACS cause atypical and late-onset forms of ARSACS.

Baets J, Deconinck T, Smets K, Goossens D, Van den Bergh P, Dahan K, Schmedding E, Santens P, Rasic VM, Van Damme P, Robberecht W, De Meirleir L, Michielsens B, Del-Favero J, Jordanova A, De Jonghe P
Neurology 2010 Sep 28;75(13):1181-8. doi: 10.1212/WNL.0b013e3181f4d86c. PMID: 20876471

Ataxias with autosomal, X-chromosomal or maternal inheritance.

Finsterer J
Can J Neurol Sci 2009 Jul;36(4):409-28. doi: 10.1017/s0317167100007733. PMID: 19650351

See all (6)

Diagnosis

Clinical Reasoning: A 48-Year-Old Man With Spasticity and Progressive Ataxia.

Vizcarra JA, Paul RA, Hamedani AG, Lynch DR, Aamodt WW
Neurology 2023 Oct 24;101(17):e1747-e1752. Epub 2023 Aug 18 doi: 10.1212/WNL.0000000000207658. PMID: 37596043 Free PMC Article

AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients.

Prevalence and phenotype of the c.1529C>T SPG7 variant in adult-onset cerebellar ataxia in Italy.

Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia.

Shao YH, Choquet K, La Piana R, Tétreault M, Dicaire MJ; Care4Rare Canada Consortium, Boycott KM, Majewski J, Brais B
Neurogenetics 2016 Apr;17(2):137-41. Epub 2016 Feb 26 doi: 10.1007/s10048-016-0476-2. PMID: 26915362

Mutations in SACS cause atypical and late-onset forms of ARSACS.

See all (10)

Prognosis

Interpretation challenges of novel dual-class missense and splice-impacting variant in POLR3A-related late-onset hereditary spastic ataxia.

Morales-Rosado JA, Macke EL, Cousin MA, Oliver GR, Dhamija R, Klee EW
Mol Genet Genomic Med 2020 Sep;8(9):e1341. Epub 2020 Jun 29 doi: 10.1002/mgg3.1341. PMID: 32597037 Free PMC Article

Prevalence and phenotype of the c.1529C>T SPG7 variant in adult-onset cerebellar ataxia in Italy.

Hereditary ataxias and paraplegias in Cantabria, Spain. An epidemiological and clinical study.

Polo JM, Calleja J, Combarros O, Berciano J
Brain 1991 Apr;114 ( Pt 2):855-66. doi: 10.1093/brain/114.2.855. PMID: 2043954

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Clinical prediction guides

Interpretation challenges of novel dual-class missense and splice-impacting variant in POLR3A-related late-onset hereditary spastic ataxia.

Morales-Rosado JA, Macke EL, Cousin MA, Oliver GR, Dhamija R, Klee EW
Mol Genet Genomic Med 2020 Sep;8(9):e1341. Epub 2020 Jun 29 doi: 10.1002/mgg3.1341. PMID: 32597037 Free PMC Article

Prevalence and phenotype of the c.1529C>T SPG7 variant in adult-onset cerebellar ataxia in Italy.

Hereditary ataxias and paraplegias in Cantabria, Spain. An epidemiological and clinical study.

Polo JM, Calleja J, Combarros O, Berciano J
Brain 1991 Apr;114 ( Pt 2):855-66. doi: 10.1093/brain/114.2.855. PMID: 2043954

Prevalence and pattern of spinocerebellar degenerations in northeastern Libya.

Sridharan R, Radhakrishnan K, Ashok PP, Mousa ME
Brain 1985 Dec;108 ( Pt 4):831-43. doi: 10.1093/brain/108.4.831. PMID: 4075075

See all (4)