Homozygous Machado Joseph Disease: A Case Report and Review of Literature
Bibliographic record
Abstract
The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders caused by cytosine-adenine-guanine (CAG) trinucleotide repeat expansions.Machado Joseph Disease (MJD) or SCA-3 was originally described in the Portuguese Azores islands and currently it is the most common autosomal dominant SCA worldwide.It is caused by CAG repeat expansion in the exon 10 of the MJD gene which codes for the ataxin-3 protein and maps to chromosome14q24.3-q31.The number of CAG repeats in normal individual ranges from 12 to 40 while affected individuals carry 51 to 86 CAG repeats in the disease producing allele. 1 Machado Joseph Disease is an autosomal dominant disorder resulting from presence of a disease causing CAG repeat expansion in only one allele.Homozygous cases, where the disease causing CAG repeat expansion is present in both alleles of the gene, of any autosomal dominant disease are rare; however, they can occur in regions where consanguineous marriages are common.There have been ten cases of genetically confirmed homozygous MJD described in the literature (Table ), one case of Azorean origin, one case of Brazilian origin, two cases of Japanese origin and six patients of Jewish descent from a small isolated region in Yemen.Consanguinity was reported in four of these cases; the six cases in Yemenite individuals were anonymized and therefore the exact family relationships were unreported. 2-6In addition, two siblings of Azorean origin with early onset and rapid progression of MJD were reported.They were not genetically confirmed but presumed to be homozygous as both of their parents were affected with MJD, one of the children died eight years after the onset of symptoms. 7In homozygous MJD cases, the disease course had a wide range of age at onset (4 -43 years old) with more pronounced extra pyramidal signs and pyramidal changes.The disease appears to be especially severe in the pediatric population.After normal development, these children had regression in motor skills, bulbar symptoms (difficulty swallowing, dysarthria), extrapyramidal changes (dystonia, bradykinesia and tremor), upper motor neuron signs and ataxia.Five years after onset the affected individuals became nonambulatory and were bedridden.Two patients with disease onset at the age of 16 years and 28 years presented with the development of spasticity, dysphagia, dysarthria, nystagmus and severe generalized dystonia and became nonambulatory within four years. 3,4The latest onset of homozygous MJD described was 43-years-old and the patient presented with rapid eye movement behavior disorder followed by ataxia, bulbar changes, mild spasticity and psychiatric symptoms. 6None of these cases described exhibited sensory changes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.010 | 0.007 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.002 | 0.004 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.004 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".