G01 Molecular testing for huntington disease and the risk of disclosure of unsolicited pre-symptomatic status: a recurring theme

Abstract Background Huntington disease prevalence was first estimated in Grampian, northern Scotland in 1984. Molecular testing has since increased ascertainment. Objective To estimate the prevalence of manifest Huntington disease and identified pre-symptomatic gene expansion carriers (IPGEC) in northern Scotland, and estimate the magnitude of biases in prevalence studies that rely upon routine coding in primary care records. Methods Cases were ascertained using North of Scotland genetic laboratory, clinic, and hospital records. Prevalence was calculated for manifest and IPGEC on 01/07/2016 and 01/01/2020 and compared with local published data. Results The prevalence of manifest Huntington disease in northern Scotland in 2020 was 14.6 (95% CI 14.3–15.3) per 100,000, and of IPGEC was 8.3 (95% CI 7.8–9.2) per 100,000. Whilst the population of northern Scotland decreased by 0.05% between 2016 and 2020, the number of manifest and identified pre-symptomatic gene expansion carriers increased by 7.4% and 23.3%, respectively. Manifest disease in Grampian increased by 45.9% between 1984 and 2020. More women than men had a diagnosis. General Practice coding underestimated symptomatic molecularly confirmed prevalence by 2.2 per 100,000 people. Conclusion Even in an area with previously high ascertainment, there has been a 45.9% increase in manifest Huntington disease over the last 30 years. Within our catchment area, prevalence varies between health board regions with similar community-based services. Such variation in prevalence could have major drug cost and service delivery implications, especially if expensive, complexly administered therapies prove successful. Health services should gather accurate population-based data on a regional basis to inform service planning.

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Assessing the analytic validity of molecular testing for Huntington disease using data from an external proficiency testing survey

Genetics in Medicine ◽

10.1097/gim.0b013e3182310bb5 ◽

2011 ◽

pp. 1

Author(s):

Glenn E. Palomaki ◽

C. Sue Richards

Keyword(s):

Proficiency Testing ◽

Huntington Disease ◽

Molecular Testing ◽

Using Data ◽

Analytic Validity

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

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01699-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Esther Vicente ◽

Ainara Ruiz de Sabando ◽

Fermín García ◽

Itziar Gastón ◽

Eva Ardanaz ◽

...

Keyword(s):

Rare Diseases ◽

Huntington Disease ◽

Late Onset ◽

Age At Onset ◽

Population Based ◽

Molecular Testing ◽

Mortality Trends ◽

Predictive Values ◽

Diagnostic Codes ◽

Incidence And Mortality

Abstract Background There 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). Methods HD 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. Results Overall 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. Conclusion HD 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.

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