Homozygous Machado Joseph Disease: A Case Report and Review of Literature
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| Bibliométrie | 0,010 | 0,007 |
| Études des sciences et des technologies | 0,002 | 0,002 |
| Communication savante | 0,002 | 0,004 |
| Science ouverte | 0,003 | 0,002 |
| Intégrité de la recherche | 0,004 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,004 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».