Prevalence Of Huntington's Disease Research Articles

An exploration of the genetics of the mutant Huntingtin (mHtt) gene in a cohort of patients with chorea from different ethnic groups in sub-Saharan Africa.

Africans are underrepresented in Huntington's disease (HD) research. A European ancestor was postulated to have introduced the mutant Huntingtin (mHtt) gene to the continent; however, recent work has shown the existence of a unique Htt haplotype in South-Africa specific to indigenous Africans. We aimed to investigate the CAG trinucleotide repeats expansion in the Htt gene in a geographically diverse cohort of patients with chorea and unaffected controls from sub-Saharan Africa. We evaluated 99 participants: 43 patients with chorea, 21 asymptomatic first-degree relatives of subjects with chorea, and 35 healthy controls for the presence of the mHtt. Participants were recruited from 5 African countries. Additional data were collected from patients positive for the mHtt gene; these included demographics, the presence of psychiatric and (or) cognitive symptoms, family history, spoken languages, and ethnic origin. Additionally, their pedigrees were examined to estimate the number of people at risk of developing HD and to trace back the earliest account of the disease in each region. HD cases were identified in all countries. Overall, 53.4% of patients with chorea were carriers for the mHTT; median tract size was 45 CAG repeats. Of the asymptomatic relatives, 28.6% (6/21) were carriers for the mHTT; median tract size was 40 CAG. No homozygous carries were identified. Median CAG tract size in controls was 17 CAG repeats. Men and women were equally affected by HD. All patients with HD-bar three who were juvenile onset of <21 years-were defined as adult onset (median age of onset was 40 years). HD transmission followed an autosomal dominant pattern in 84.2% (16/19) of HD families. In familial cases, maternal transmission was higher 52.6% (10/19) than paternal transmission 36.8% (7/19). The number of asymptomatic individuals at risk of developing HD was estimated at ten times more than the symptomatic patients. HD could be traced back to the early 1900s in most African sites. HD cases spread over seven ethnic groups belonging to two distinct linguistic lineages separated from each other approximately 54-16kya ago: Nilo-Sahara and Niger-Congo. This is the first study examining HD in multiple sites in sub-Saharan Africa. We demonstrated that HD is found in multiple ethnic groups residing in five sub-Saharan African countries including the first genetically confirmed HD cases from Guinea and Kenya. The prevalence of HD in the African continent, its associated socio-economic impact, and genetic origins need further exploration and reappraisal.

Huntington's disease prevalence in Asia: a systematic review and meta-analysis.

The epidemiological studies on Huntington's disease (HD) in the Asian population suggest that prevalence rates are significantly lower than in the Western population. We conducted a systematic review of epidemiological studies of HD in Asia to compare the level of impact of the disease on the Asian population. Original articles and reviews about HD prevalence in the Asian population were found through databases such as Embase, Medline, and PsychInfo. Relevant articles were analysed by scrutinising of references, including specific key words. A meta-analysis was performed on prevalence rates to find the degree of similarities with I2. Point Prevalence was measured as the number of people affected by HD in a 100,000 population and expressed as Point Prevalence (PP)= Number of people affected/100,000 with 95% Confidence Intervals (CI95). Results from the random-effect meta-analysis show the highest point prevalence of HD in the Middle East with PP=4.0 (CI95=2.90-5.30). The lowest point prevalence was found in the Chinese population with PP=0.25 (CI95=0.16-0.36). Europe remains at a high prevalence compared to Asian countries with PP=1.00 (CI95=0.82-1.19). The overall prevalence in Asia is PP=0.70 (CI95=0.44-1.0). Our study reveals that HD disease affects the population of Asia to a lesser extent than in Europe. The plausible explanation for differences in prevalence is that in some countries, the affected individuals will not self-refer to HD screening for fear of social stigma, negative influence in marriage, and lack of genetic and neurological testing. Another explanation is that studies that used genetic testing exclusively were able to identify the CAG repeats, subgroups of CAG repeat A1 & A2, and haplogroup C, which has less predisposition to high HD prevalence in Asians compared to the Caucasian population.

Increased 10-Year Prevalence of Huntington's Disease in South Korea: An Analysis of Medical Expenditure Through the National Healthcare System.

This study aimed to determine the updated 10-year prevalence of Huntington's disease (HD) in South Korea and the medical and economic burdens across the duration of the disease. Data from the National Health Insurance database during 2010-2019 were analyzed. We identified HD cases using predefined criteria. Information on age at diagnosis, sex, and common nonneurological comorbidities were collected. We analyzed individual patterns of the use of medical services and yearly medical expenditure. Incidence rates, 10-year prevalence rates, and longitudinal medical expenditure changes were assessed. New patients with HD (average=152.10) were detected every year, with an annual incidence of 0.29 per 100,000. The estimated 10-year prevalence of HD was 2.2 per 100,000. The most common ages at the time of diagnosis were 50-59 years (23.3%). In 2019, 56.4% of patients with HD were followed-up at referral or general hospitals, and 32.2% were managed at long-term-care hospitals. The annual medical cost for an individual was KRW 6,569,341±895,097 (mean±SD) (mean≈USD 5,653). Medical expenditure was the highest in those aged 60-79 years, and lowest in those younger than 30 years. However, in all age groups, the annual medical expenditure was highest during the 9 years following a diagnosis. This study found that the actual prevalence of HD in South Korea was higher than previously thought and that patients are in a situation with high medical expenditure that persists over time.

Economic burden of Huntington disease in Europe and the USA: Results from the Huntington's Disease Burden of Illness study.

The prevalence of Huntington disease (HD) has increased over time; however, there is a lack of up-to-date evidence documenting the economic burden of HD by disease stage. This study provides an estimate of the annual direct medical, nonmedical, and indirect costs associated with HD from participants in the Huntington's Disease Burden of Illness (HDBOI) study in five European countries and the USA. The HDBOI is a retrospective, cross-sectional study. Data collection was conducted between September 2020 and May 2021. Participants were recruited by their HD-treating physicians and categorized as early stage (ES), mid stage (MS), or advanced stage (AS) HD. Data were collected via three questionnaires: a case report form, completed by physicians who collected health care resource use associated with HD to compute direct medical cost, and optional patient and caregiver questionnaires, which included information used to compute nondirect medical and indirect costs. Country-specific unit cost sources were used. HDBOI cost estimates were €12,663 (n= 2094) for direct medical costs, €2984 (n= 359) for nondirect medical costs, and €47,576 (n= 436) for indirect costs. Costs are higher in patients who are at later stages of disease; for example, direct medical costs estimates were €9220 (n= 846), €11,885 (n= 701), and €18,985 (n= 547) for ES, MS, and AS, respectively. Similar trends were observed for nondirect and indirect costs. Costs show large variations between patients and countries. Cost estimates from the HDBOI study show that people with HD and their caregivers bear a large economic burden that increases as disease progresses.

Prevalence and Incidence of Huntington's Disease: An Updated Systematic Review and Meta-Analysis.

The incidence and prevalence of Huntington's disease (HD) based on a systematic review and meta-analysis of 20 studies published from 1985 to 2010 was estimated at 0.38 per 100,000 person-years (95% confidence interval [CI], 0.16-0.94) and 2.71 per 100,000 persons (95% CI, 1.55-4.72), respectively. Since 2010, there have been many new epidemiological studies of HD. We sought to update the global estimates of HD incidence and prevalence using data published up to February 2022 and perform additional analyses based on study continent. Medline and Embase were searched for epidemiological studies of HD published between 2010 and 2022. Risk of bias was assessed using a quality assessment tool. Estimated pooled prevalence or incidence was calculated using a random-effects meta-analysis. A total of 33 studies published between 2010 and 2022 were included. Pooled incidence was 0.48 cases per 100,000 person-years (95% CI, 0.33-0.63). Subgroup analysis by continent demonstrated a significantly higher incidence of HD in Europe and North America than in Asia. Pooled prevalence was 4.88 per 100,000 (95% CI, 3.38-7.06). Subanalyses by continent demonstrated that the prevalence of HD was significantly higher in Europe and North America than in Africa. The minor increase in prevalence (more so than incidence) demonstrated in this updated review could relate to the enhanced availability of molecular testing, earlier diagnosis, increased life expectancy, and de novo mutations. Limitations include variable case ascertainment methods and lacking case validation data. © 2022 Her Majesty the Queen in Right of Canada. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Reproduced with the permission of the Minister of Public Health Agency of Canada.

Complexities in Genetic Counseling and Testing of Huntington's Disease: A Perspective from India.

Huntington's Disease (HD) is an autosomal dominant, progressive neuropsychiatric illness caused by CAG repeat expansion. The high penetrance of the mutation and limited treatment options make it challenging for patients and caretakers. Proper counseling enables families to cope better and make informed life choices. To explore some complex issues in genetic counseling and testing (GCAT) in HD. Vignettes of patients who underwent genetic testing along with pre and post-test counseling at our GCAT clinic. Case 1: Diagnosis of juvenile HD meant that the healthy parent was an obligate carrier of the mutation. Case 2: Consanguinity resulted in a dense prevalence of HD and >50% risk for the progeny. Case 3: Predictive testing in youth with healthy parents but affected uncles and aunts revealed a HD expansion. HD can present with complex inheritance patterns and proper counseling is necessary for better outcomes.

Validation of diagnostic codes and epidemiologic trends of Huntington disease: a population-based study in Navarre, Spain

BackgroundThere is great heterogeneity on geographic and temporary Huntington disease (HD) epidemiological estimates. Most research studies of rare diseases, including HD, use health information systems (HIS) as data sources. This study investigates the validity and accuracy of national and international diagnostic codes for HD in multiple HIS and analyses the epidemiologic trends of HD in the Autonomous Community of Navarre (Spain).MethodsHD cases were ascertained by the Rare Diseases Registry and the reference Medical Genetics Centre of Navarre. Positive predictive values (PPV) and sensitivity with 95% confidence intervals (95% CI) were estimated. Overall and 9-year periods (1991–2017) HD prevalence, incidence and mortality rates were calculated, and trends were assessed by Joinpoint regression.ResultsOverall PPV and sensitivity of combined HIS were 71.8% (95% CI: 59.7, 81.6) and 82.2% (95% CI: 70.1, 90.4), respectively. Primary care data was a more valuable resource for HD ascertainment than hospital discharge records, with 66% versus 50% sensitivity, respectively. It also had the highest number of “unique to source” cases. Thirty-five per cent of HD patients were identified by a single database and only 4% by all explored sources. Point prevalence was 4.94 (95% CI: 3.23, 6.65) per 100,000 in December 2017, and showed an annual 6.1% increase from 1991 to 1999. Incidence and mortality trends remained stable since 1995–96, with mean annual rates per 100,000 of 0.36 (95% CI: 0.27, 0.47) and 0.23 (95% CI: 0.16, 0.32), respectively. Late-onset HD patients (23.1%), mean age at onset (49.6 years), age at death (66.6 years) and duration of disease (16.7 years) were slightly higher than previously reported.ConclusionHD did not experience true temporary variations in prevalence, incidence or mortality over 23 years of post-molecular testing in our population. Ascertainment bias may largely explain the worldwide heterogeneity in results of HD epidemiological estimates. Population-based rare diseases registries are valuable instruments for epidemiological studies on low prevalence genetic diseases, like HD, as long as they include validated data from multiple HIS and genetic/family information.

Prevalence of Huntington's disease in Southern Sardinia, Italy

BackgroundThe frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non Asian populations. In Italy, two recent studies performed in Ferrara county and Molise provided different prevalence estimates, varying from 4.2 × 105 to 10.8 × 105. Here we present a study performed in the Southern part of Sardinia, a large Italian mediterranean island that is considered a genetic isolate. MethodsThe study area included the two neighbouring counties of South Sardinia and Cagliari with 353,830 and 431,955 inhabitants respectively on December 31st, 2017 (prevalence date). Case-patients were ascertained through multiple sources in Sardinia and Italy. ResultsWe identified 54 individuals with HD, of whom 47 were alive on prevalence date. The resulting prevalence rate was 5.98 × 105 in the overall study area, however with marked variations between South Sardinia and Cagliari (9.6 × 105 vs. 3.0 × 105, p = 0.02). In the two study areas, we found similar CAG repeat length in normal alleles (17.5 ± 2.1 vs. 17.7 ± 2.2, p = 0.5). ConclusionsThe overall prevalence of HD in Sardinia is close to the correspondent estimates in Europeans. Our findings also highlighted the possibility of local microgeographic variations in the epidemiology of HD.

Distribution of the HTT Gene A1 and A2 Haplotypes Worldwide: A Systematic Review.

Huntington's disease (HD)(MIM:143100) is an severe autosomal dominant neurodegenerative disease caused by the dynamic expansion of CAG trinucleotides (> 35) in the HTT gene [Genomic Coordinates- (GRCh38):4:3,074,680-3,243,959]. The aim of this systematic review was to investigate the reported associations between the frequencies of the A1 and A2 haplotypes in HD-affected and non-affected populations from different countries on different continents, in order to demonstrate the overall profile of these haplotypes worldwide, pointing towards the most frequent haplotypes that could be useful for HTT mutant-specific allele silencing in different populations. Publications in MEDLINE (PubMed) and Embase from the last 10 years (PROSPERO CRD42018115282) were assessed. A total of 20 articles from 113 were selected for evaluation in their entirety, and eight were eligible for this study. Regardless of the size of the CAG tract, the articles included in this review demonstrate that populations with high HD prevalence present higher frequencies of the A1 or A2 haplotypes than populations exhibiting low HD prevalence, even when similar average CAG numbers are noted. Based on the presented articles, we suggest that the haplotypic profile is more closely related to the ancestral origin than to the size of the CAG tract. The identification of populations presenting a higher frequency of high-risk genotypes can contribute to more accurate genetic counseling, in addition to providing knowledge on HD epidemiology. According to the continued progress in the development of specific genetic silencing therapies by different research groups and pharmaceutical companies, such as haplotype targeting strategies for allele-specific HTT suppression, we conclude that the definition of haplotypes in phase with CAG expansions will contribute to the design of gene-silencing drugs specific for different populations worldwide.

Huntington's disease with childhood and adolescent onset: course of disease, clinical presentation and diagnostic challenges

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a gene mutation in chromosome 4 that leads to an expansion of CAG - triplet repeats. It occurs mainly between the age of 30 and 50. Only less than 10 % of HD patients are younger than 20 years. In contrast to adult patients young HD patients show more often psychiatric and cognitive symptoms at disease onset than chorea. One third of the children with HD develops an epilepsy.We present 6 children diagnosed with HD in different stages of childhood. We describe first symptoms as well as genetic characteristics and other distinctive features.Both, the clinical presentation and the course of HD in childhood differ from HD in adults. In adolescents the clinical symptoms at onset are often psychiatric (like depression or attention deficit disorder). Choreatic movements typical for adult HD patients are missing.Due to the low prevalence of HD in childhood and the variability of clinical symptoms the process of diagnosing HD in children is difficult. Very often the diagnosis is made years after the first symptoms. Early diagnosis, however, is often important for managing social problems and problems in school.

Prevalence of Huntington Disease in Italy: a systematic review and meta-analysis

Worldwide prevalence of Huntington’s disease (HD) is quite heterogenous. As Italy is characterized by significant genetic heterogeneity, with presumptive differences between Italian regions, this review was undertaken to define available data of HD prevalence in Italy, to assess geographic heterogeneity, and reconcile possible variation in HD prevalence rates with the availability of genetic testing.Methods.In total, 14 relevant studies were identified from Medline/Embase, and analysis of available Italian regional reports on rare diseases.Results.A cumulative prevalence of 3.9/100,000 inhabitants (95% Confidence Interval 3.0 – 5.0) was identified, with apparently higher rates in the last decades (4.1/100,000 vs. 3.0/100,000). The lowest rates were among the resident of the Oristano province in Sardinia, while the highest were reported in three mountainous and rather isolated areas (i.e. Molise, San Marino, Varese; all well over 10 cases/100,000 inhabitants). These differences cannot be not fully explained by varying approaches to case-ascertainment or diagnosis, and a possible “founder effect” may therefore be extensively advocated.Discussion.The prevalence of HD in retrieved Italian reports varied up to almost tenfold between different geographical regions. Even though such variation can in part be attributed to differences in case-ascertainment and/or diagnostic criteria, there is consistent evidence of significant founder effects in certain areas such as the provinces of Varese, the Republic of San Marino, and the region od Molise – all of them with estimates > 10/100,000 cases. As our estimates suggest that up to half of Italian HD cases may be still waiting, Public Health approach should improve diagnostic rates in order to guaranteeing palliative and symptomatic interventions (antidepressants, antipsychotics, anti-choreiform medications) to all individuals and their families.

Prevalence of Parkinson Disease in Italy: a systematic review and meta-analysis.

Introduction:Parkinson’s disease (PD) is a common disease of unknown etiology. Even though accurate information on the epidemiology of PD is critical for defining appropriate health policies, epidemiological data on Parkinson’s disease (PD) in Italy are often defined as scant or conflicting. Our study attempted to provide an overview on the prevalence of (PD) by means of a systematic review and metanalysis of existing data.Material and methods:We searched into two different databases (PubMed and EMBASE), focusing on studies reporting the prevalence of PD in Italy. Data were extracted using a standardized assessment form, and results of such analyses were systematically reported, summarized and compared.Results:A total of 16 studies were eventually included in the analyses, with a prevalence rate of 193.7/100,000. Available reports were heterogeneous both in design and in eventual figures, and also prevalence estimates were affected by substantial heterogeneity. Interestingly, prevalence rates ranged from 37.8/100,000 inhabitants in subjects aged 0 to 64 years, to 578.7 in age group 65 to 75 years, and 1235.7 in age group 75 years or older. PD was significantly associated with male sex, but only in older age groups (i.e. Odds Ratio, OR 1.37 95%CI 1.22-1.53, and OR 1.31, 95%CI 1.21-1.42 for age groups 65-74 years and 75 years or more, respectively).Discussion and conclusion:While the observed variations in prevalence rates may result from environmental or genetic factors, differences in methodologies for case ascertainment and diagnostic criteria may have significantly affected our estimates. As a consequence, the comparability of existing studies is limited.

Addressing the Value of Multidisciplinary Clinical Care in Huntington's Disease: A Snapshot of a New Huntington's Disease Center.

Clinical care for Huntington's disease (HD) is often provided in experienced centers that provide multidisciplinary care. However, the value of these centers and their uptake by HD families remain unknown. To describe the services provided by a new HD center, including estimates of capture of the population served. Retrospective review of a HD Center launched in 2015, including quantitative and qualitative data on clinic visits, demographic and clinical data. We observed a rapid and ongoing growth on the annual number of clinic encounters, with high demand for in-clinic multidisciplinary care. Using census data and estimates of HD prevalence, we determined that we served about 20% of local patients with HD. Most HD patients received pharmacological treatment for psychiatric symptoms, and over half were treated for chorea. About 25% of new HD diagnoses were on patients without family history of HD. Finally, the demand for predictive testing in at risk individuals significantly increased following the press release reporting the successful completion of the Ionis-HTTRx (RG 6042) trial. This report indicates a high demand for multidisciplinary care by HD families, supporting its value, providing a snapshot of the organization and function of a single center. Furthermore, it demonstrates how dissemination of news related to research advances influence clinical behavior. Reporting similar information from other HD centers to would provide us with a more global view of the status of HD care across multiple geographical areas.

Haplotype analysis encompassing HTT gene in Chinese patients with Huntington's disease.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder with varied prevalence in different populations, which may be associated with specific haplotypes. This study aimed to explore the haplotypes encompassing the HTT gene in the Chinese population. A total of 406 individuals with HD and 59 normal relatives from 253 families with HD were enrolled. A total of 29 tagsingle nucleotide polymorphisms (tSNPs) were selected and genotyped for the haplotype analysis. In stage one, we used 18 tSNPs to replicate the distribution of three major haplogroups (A, B, C). We found that risk-associated haplogroup variants A1 and A2, enriched on Caucasian HD chromosomes, were totally absent from both Chinese HD and control chromosomes, and the distributions of haplogroups between HD and control chromosomes were similar. Therefore, in stage two, we used 29 tSNPs (including the18 tSNPs) to define new haplogroups (I, II, III) and found that haplogroup I accounted for 61.4% on HD chromosomes and 34.4% on control chromosomes, indicating that haplogroup I was enriched on Chinese HD chromosomes. This is the first haplotype analysis encompassing HTT in the Chinese population. The results contribute to explaining the low prevalence of HD in China and provide a better understanding of genetic diversity in the HTT region.

Minimal prevalence of Huntington's disease in the South of Brazil and instability of the expanded CAG tract during intergenerational transmissions.

Huntington’s disease (HD) is due to dominant expansions of the CAG repeat of the HTT gene. Meiotic instability of the (CAG)n might impact the disorder frequency. We report on HD minimal prevalence in Rio Grande do Sul (RS) state, Brazil, and on intergenerational instability of the (CAG)n in HD families. Symptomatic and at-risk subjects from 179 HD families were ascertained between 2013 and 2016. Clinical, molecular and family history data were obtained. Expanded (CAG)n length differences between parent and child (delta-expanded-(CAG)n) were calculated. Effect of parental age on the (CAG)n instability upon transmission was inferred by correlating delta-expanded-(CAG)n between siblings to their age differences. HD minimal prevalence in RS state was estimated as 1.85:100,000 inhabitants. Alleles with (CAG)27-35 were found on 21/384 non-disease associated chromosomes (5.5%); among 253 expanded alleles, four (1.6%) were within reduced penetrance range with (CAG)36-39. In 32 direct transmissions, mean instability was larger among paternal than maternal transmissions. In direct transmissions and in 51 sibling pairs, parental age at the time of child birth were not correlated with delta-expanded-(CAG)n. Briefly, HD prevalence in RS state was lower than those reported for European populations. Expanded (CAG)n transmissions were unstable and not associated to parental age.

The molecular epidemiology of Huntington disease is related to intermediate allele frequency and haplotype in the general population.

Huntington disease (HD) is the most common monogenic neurodegenerative disorder in populations of European ancestry, but occurs at lower prevalence in populations of East Asian or black African descent. New mutations for HD result from CAG repeat expansions of intermediate alleles (IAs), usually of paternal origin. The differing prevalence of HD may be related to the rate of new mutations in a population, but no comparative estimates of IA frequency or the HD new mutation rate are available. In this study, we characterize IA frequency and the CAG repeat distribution in fifteen populations of diverse ethnic origin. We estimate the HD new mutation rate in a series of populations using molecular IA expansion rates. The frequency of IAs was highest in Hispanic Americans and Northern Europeans, and lowest in black Africans and East Asians. The prevalence of HD correlated with the frequency of IAs by population and with the proportion of IAs found on the HD-associated A1 haplotype. The HD new mutation rate was estimated to be highest in populations with the highest frequency of IAs. In European ancestry populations, one in 5,372 individuals from the general population and 7.1% of individuals with an expanded CAG repeat in the HD range are estimated to have a molecular new mutation. Our data suggest that the new mutation rate for HD varies substantially between populations, and that IA frequency and haplotype are closely linked to observed epidemiological differences in the prevalence of HD across major ancestry groups in different countries.

Epidemiology of Huntington disease in Cyprus: A 20-year retrospective study.

Huntington disease (HD) is most prevalent among populations of western European descent and isolated populations where founder effects may operate. The aim of this study was to examine the epidemiology of HD in Cyprus, an island in southern Europe with extensive western European colonization in the past. All registered HD patients in the Cyprus, since 1994, were included. Detailed pedigrees and clinical information were recorded and maps, showing the geographic distribution of HD, were constructed. Requests for genetic testing were also examined. The project identified 58 clinically manifested cases of HD belonging to 19 families. The 16 families of Cypriot origin were concentrated in a confined geographical cluster in southeast Cyprus. In 2015, prevalence of symptomatic HD was 4.64/100 000 population, while incidence was 0.12/100 000 person-years. Prevalence displayed a marked increase during the past 20 years. Disease characteristics of HD patients were similar to those reported in western European populations. Lastly, the uptake of predictive and/or prenatal testing was limited. HD disease characteristics, incidence and prevalence in Cyprus were comparable to western European populations. Together with the geographical clustering observed, these results support the possibility for a relatively recent founder effect of HD in Cyprus, potentially of western European origin.

Epidemiological Study of Huntington's Disease in the Province of Ferrara, Italy

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of CAG triplet repeat. We aimed to reappraise HD epidemiology in a northern Italian population, in relation to introduction of genetic testing. Methods: Through ICD-9M code 333.4 and medical fare exemption code RF0080, HD cases were identified from administrative health data and medical records from the Units of Neurology and Genetics, Ferrara University Hospital, and from other provincial neurological structures. Results: HD mean annual incidence rate in 1990-2009 was 0.3 per 100,000 (95% CI 0.2-0.5). All incident cases were found to have symptoms of the disease's classic form, and neither juvenile nor the rigid Westphal variant was detected. The mean (SD) age at onset was 50.2 (12.7 years; range 32-82 years), 54.9 (14.6) for men and 45.8 (9.4) for women. On prevalence day, December 31, 2014, HD prevalence was 4.2 per 100,000 (95% CI 2.4-7.0), with a male:female ratio of 1:2. Conclusions: The prevalence and incidence of HD in our population were lower than the prevalence and incidence reported for other European and Italian populations, but higher compared to those of Asia, Africa, and Eastern Europe. Compared to previous studies, HD incidence and prevalence did not change significantly.

Discrepancy in prevalence of Huntington's disease in two Swedish regions.

Huntington's disease (HD) is a neurodegenerative disease with an autosomal dominant pattern of inheritance. The prevalence varies between different geographical regions with an estimated average in Europe of about 6/100000. Parts of northern Sweden are known to have an accumulation of HD, but no prevalence studies have been undertaken for 50years. The aim of this study was to estimate the prevalence of HD in the two different Swedish counties of Jämtland and Uppsala and compare them with the reported prevalence in Europe. Patients registered with the diagnosis of HD were identified through medical records in each county. Presymptomatic patients were excluded. We also compared the annual number of individuals with HD registered in the database of the National Board of Health and Welfare in these regions, with all of Sweden. The prevalence of HD was found to be 22.1/100000 in Jämtland and 4.9/100000 in Uppsala county. The mean age was 62.2years and 61.8years, respectively. The annual average of patients with HD registered at inpatient care was 1.5/100000 in Jämtland, 0.44/100000 in Uppsala county, and 0.56/100000 in all of Sweden. The prevalence of patients with the diagnosis of HD is four times higher in the county of Jämtland than in the county of Uppsala, where the prevalence is more similar to the average in Europe. Our results support earlier findings of regional variations of HD prevalence with an accumulation in certain parts of northern Sweden.

The Danish HD Registry-a nationwide family registry of HD families in Denmark.

The Danish Huntington's Disease Registry (DHR) is a nationwide family registry comprising 14 245 individuals from 445 Huntington's disease (HD) families of which the largest family includes 845 individuals in 8 generations. 1136 DNA and/or blood samples and 18 fibroblast cultures are stored in a local biobank. The birthplace of the oldest HD carrier in each of the 261 families of Danish origin was unevenly distributed across Denmark with a high number of families in the middle part of the peninsula Jutland and in Copenhagen, the capital. The prevalence of HD in Denmark was calculated to be 5-8:100 000. 1451 individuals in the DHR had the size of the HTT CAG repeat determined of which 975 had 36 CAG repeats or more (mean ± SD: 43,5 ± 4,8). Two unrelated individuals were compound heterozygous for alleles ≥36 CAGs, and 60 individuals from 34 independent families carried an intermediate allele.