Spinocerebellar ataxia type 2 has multiple ancestral origins.

INTRODUCTION: Spinocerebellar ataxia type 2 (SCA2) is a dominant neurodegenerative disorder due to expansions of a CAG repeat tract (CAGexp) at the ATXN2 gene. Previous studies found only one ancestral haplotype worldwide, with a C allele at rs695871. This homogeneity was unexpected, given the severe anticipations related to SCA2. We aimed to describe informative ancestral haplotypes found in South American SCA2 families. METHODS: Seventy-seven SCA2 index cases were recruited from Brazil, Peru, and Uruguay; 263 normal chromosomes were used as controls. The SNPs rs9300319, rs3809274, rs695871, rs1236900 and rs593226, and the STRs D12S1329, D12S1333, D12S1672 and D12S1332, were used to reconstruct haplotypes. RESULTS: Eleven ancestral haplotypes were found in SCA2 families. The most frequent ones were A-G-C-C-C (46.7 % of families), G-C-C-C-C (24.6 %) and A-C-C-C-C (10.3 %) and their mean (sd) CAGexp were 41.68 (3.55), 40.42 (4.11) and 45.67 (9.70) (p = 0.055), respectively. In contrast, the mean (sd) CAG lengths at normal alleles grouped per haplotypes G-C-G-A-T, A-G-C-C-C and G-C-C-C-C were 22.97 (3.93), 23.85 (3.59), and 30.81 (4.27) (p < 0.001), respectively. The other SCA2 haplotypes were rare: among them, a G-C-G-A-T lineage was found, evidencing a G allele in rs695871. CONCLUSION: We identified several distinct ancestral haplotypes in SCA2 families, including an unexpected lineage with a G allele at rs695871, a variation never found in hundreds of SCA2 patients studied worldwide. SCA2 has multiple origins in South America, and more studies should be done in other regions of the world.

Correlation between ABO blood type, susceptibility to SARS-CoV-2 infection and COVID-19 disease severity: A systematic review

ABSTRACT Objectives: To verify the association between the ABO blood type and the risk of SARS-CoV-2 infection and COVID-19 disease severity. Methods: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the 2020 PRISMA Checklist and flow diagram, and articles selected for review were analyzed using the Newcastle-Ottawa Quality Rating Scale. The research question was: "Would the ABO blood group influence the risk of infection and clinical course of patients infected with SARS-CoV-2?", The following databases were used: Embase, PubMed, Virtual Health Library (VHL), Web of Science, Science-Direct and Scopus. The protocol for this review was registered in the Prospective Register of Systematic Reviews (PROSPERO), number CRD42021245945. Results: We found 798 articles across PubMed, Embase, Scopus, Web of Science, Science Direct and Virtual Health Library and 54 articles were included in the final analysis. Among 30 studies evaluating the risk of COVID-19 infection, 21 found significant correlations with ABO blood groups, 14 of them revealing an increased risk in blood group A and 15 studies showing a decreased risk in blood group O. Most studies found no significant correlation with disease severity or mortality. Conclusion: The qualitative assessment of available information suggests that blood group A may be a risk factor for COVID-19 infection and that blood group O may have a protective effect. We were unable to determine a clear association between the ABO blood group and mortality. These conclusions are based on highly heterogenous evidence.

Correlation between ABO blood type, susceptibility to SARS-CoV-2 infection and COVID-19 disease severity: A systematic review.

OBJECTIVES: To verify the association between the ABO blood type and the risk of SARS-CoV-2 infection and COVID-19 disease severity. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the 2020 PRISMA Checklist and flow diagram, and articles selected for review were analyzed using the Newcastle-Ottawa Quality Rating Scale. The research question was: "Would the ABO blood group influence the risk of infection and clinical course of patients infected with SARS-CoV-2?", The following databases were used: Embase, PubMed, Virtual Health Library (VHL), Web of Science, ScienceDirect and Scopus. The protocol for this review was registered in the Prospective Register of Systematic Reviews (PROSPERO), number CRD42021245945. RESULTS: We found 798 articles across PubMed, Embase, Scopus, Web of Science, Science Direct and Virtual Health Library and 54 articles were included in the final analysis. Among 30 studies evaluating the risk of COVID-19 infection, 21 found significant correlations with ABO blood groups, 14 of them revealing an increased risk in blood group A and 15 studies showing a decreased risk in blood group O. Most studies found no significant correlation with disease severity or mortality. CONCLUSION: The qualitative assessment of available information suggests that blood group A may be a risk factor for COVID-19 infection and that blood group O may have a protective effect. We were unable to determine a clear association between the ABO blood group and mortality. These conclusions are based on highly heterogenous evidence.

Nutritional status and eating habits of patients with hereditary ataxias: a case-control study.

INTRODUCTION: Hereditary Ataxias (HAs) comprise a wide spectrum of genetically determined neurodegenerative diseases with progressive ataxia as the main symptom. Few studies have evaluated nutritional profile in HA patients and most of these focused on specific ataxia subtypes. The objectives of this study were: (1) to investigate whether hereditary ataxias were associated with changes in energy expenditure, body composition and dietary intake; (2) to verify differences in these variables according to ataxia subtype, sex, age, and disease severity. METHODS: Thirty-eight hereditary ataxia patients from two neurology centers in Northeastern Brazil and 38 controls were evaluated. Body composition was assessed with bio-impedance analysis and dietary intake was estimated with a validated questionnaire (24-hour dietary recall). RESULTS: Mean body mass index (BMI) was lower in HA compared to controls (p = 0.032). Hereditary ataxia patients showed lower protein intake, higher frequency of dysphagia and higher incidence of nausea and diarrhea. The difference in average estimated caloric intake did not reach statistical significance (2359kcal ± 622 in patients × 2713kcal ± 804 in controls, p = 0.08). Disease severity measured by the SARA scale was not associated with BMI, nor was ataxia subtype (autosomal dominant × non-autosomal dominant ataxias). CONCLUSION: Hereditary ataxia patients have lower BMI compared to healthy controls. There was no difference in this cohort between dominant or non-dominant ataxia regarding BMI. Weight loss may be a common finding among hereditary ataxias and may affect the quality of life in these patients.

Moyamoya associated with Turner syndrome in a patient with type 2 spinocerebellar ataxia-Occam's razor or Hickam's dictum: a case report.

BACKGROUND: Turner syndrome (TS) is a rare condition associated with a completely or partially missing X chromosome that affects 1 in 2500 girls. TS increases the risk of autoimmune diseases, including Graves' disease (GD). Moyamoya disease is a rare cerebral arteriopathy of unknown etiology characterized by progressive bilateral stenosis of the internal carotid artery and its branches. Both TS and GD have been associated with Moyamoya. Type 2 spinocerebellar ataxia (SCA2) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in ATXN2. We present the first case of Moyamoya syndrome in a patient with a previous diagnosis of TS and GD who tested positive for SCA2 and had imaging findings compatible with an overlap of SCA2 and Moyamoya. CASE PRESENTATION: A 43-year-old woman presented with mild gait imbalance for 2 years. Her family history was positive for type 2 spinocerebellar ataxia (SCA2). She had been diagnosed with Turner Syndrome (45,X) and Graves disease three years before. Brain MRI revealed bilateral frontal and parietal cystic encephalomalacia in watershed zones, atrophy of pons, middle cerebellar peduncles and cerebellum. MR angiography showed progressive stenosis of both internal carotid arteries with lenticulostriate collaterals, suggestive of Moya-Moya disease. Molecular analysis confirmed the diagnosis of SCA2. CONCLUSIONS: With increased availability of tools for genetic diagnosis, physicians need to be aware of the possibility of a single patient presenting two or more rare diseases. This report underscores the modern dilemmas created by increasingly accurate imaging techniques and available and extensive genetic testing.