Home › Research › Clinical safety
Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations
Behrens MI, Brüggemann N, Chana P, Venegas P, Kägi M, Parrao T, Orellana P, Garrido C et al.. Movement disorders : official journal of the Movement Disorder Society, 2010-09-01
Topic: Brain proteins, microglia and lab models
We report the clinical features of the original Chilean family with Kufor-Rakeb syndrome (KRS) that led to the discovery of the ATP13A2 gene at the PARK9 locus. KRS is a rare juvenile-onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial-faucial-finger minimyoclonus. Neurological and neuropsychological examination during a 10-year period, videotaping, neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound-heterozygous ATP13A2 mutations, had normal development until ages ∼10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial-faucial-finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 ± 5.5 (mean ± SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression. The marked caudate and lenticular nucleus T2*-hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation.
Key findings
- Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia.
- T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally.
- There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression.
- The marked caudate and lenticular nucleus T2*-hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation.
Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Movement disorders : official journal of the Movement Disorder Society) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20683840) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Behrens, M. I., Brüggemann, N., Chana, P., Venegas, P., Kägi, M., Parrao, T., et al. (2010). Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. Movement disorders : official journal of the Movement Disorder Society. https://doi.org/10.1002/mds.22996
Vancouver
Behrens MI, Brüggemann N, Chana P, Venegas P, Kägi M, Parrao T, et al. Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. Movement disorders : official journal of the Movement Disorder Society. 2010. doi:10.1002/mds.22996. PMID: 20683840.
BibTeX
@article{behrens2010-20683840,
author = {Behrens, M. I. and Brüggemann, N. and Chana, P. and Venegas, P. and Kägi, M. and Parrao, T. and Orellana, P. and Garrido, C. and others},
title = {{Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations}},
journal = {Movement disorders : official journal of the Movement Disorder Society},
year = {2010},
doi = {10.1002/mds.22996},
pmid = {20683840},
url = {https://doi.org/10.1002/mds.22996}
}
Related studies in Clinical safety
Also tagged “bodies”
1,017 studies in the library carry the topic tag “bodies”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,017 tagged studies.