Population-based prevalence of rare diseases in Jeju, Korea: a 2021 analysis using NHIS data

Ki Soo Kang; Jung-Kook Song

doi:10.22730/jmls.2025.22.2.69

J Med Life Sci > Volume 22(2); 2025 > Article

Kang and Song: Population-based prevalence of rare diseases in Jeju, Korea: a 2021 analysis using NHIS data

Original Article

Journal of Medicine and Life Science 2025;22(2):69-80.

Published online: May 28, 2025

DOI: https://doi.org/10.22730/jmls.2025.22.2.69

Population-based prevalence of rare diseases in Jeju, Korea: a 2021 analysis using NHIS data

Ki Soo Kang¹

, Jung-Kook Song²

¹Department of Pediatrics, Jeju National University Hospital, Jeju National University College of Medicine, Jeju, Republic of Korea

²Department of Preventive Medicine, Jeju National University Hospital, Jeju National University College of Medicine, Jeju, Republic of Korea

Correspondence to Jung-Kook Song Department of Preventive Medicine, Jeju National University Hospital, Jeju National University College of Medicine, 15 Aran 13-gil, Jeju 63241, Republic of Korea
Tel: 82-64-754-8115 Fax: 82-64-717-2966 E-mail: songj@jejunu.ac.kr

Received April 4, 2025 Revised April 21, 2025 Accepted April 23, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study aimed to investigate the prevalence of rare diseases in Jeju using population-based data. We analyzed 2021 data from the customized research database of the National Health Insurance Service (NHIS). Rare diseases were defined based on the designation of the Ministry of Health and Welfare as of July 1, 2021. The number of patients and claims was calculated. The crude prevalence rate per 100,000 individuals was computed using mid-year population data. Diseases were also classified by hereditary status and by system based on the Korean Standard Classification of Diseases. A total of 4,669 patients with rare diseases were identified. The crude prevalence rate was 696 per 100,000 individuals (619 for males, 774 for females). Among the 30 most frequent diseases, the rates ranged from 51 to 4 per 100,000 individuals. Pediatric prevalence was higher in males, and hereditary diseases were more common in children than in adults (38.1% vs. 15.5%). Medical Aid coverage was observed in 6.0% of patients, indicating greater economic vulnerability. Of the 640 rare diseases identified in the NHIS data (among 1,201 nationally designated diseases), only 279 (44.0%) were observed in Jeju. Rare diseases were less likely to be detected due to the small population of the region. Additionally, 8.3% of patients with rare diseases (excluding ultra-rare diseases and chromosomal abnormalities) and 25.0% of patients with ultra-rare diseases had multiple rare disease diagnoses. This is the first population-based study of the prevalence of rare diseases in Jeju. The findings provide baseline data essential for regional surveillance and policy development.

Key words: Rare diseases; Epidemiology; Incidence; Prevalence

INTRODUCTION

Rare diseases are defined by their extremely low prevalence and limited patient population, resulting in a scarcity of information and posing significant challenges to diagnosis and treatment. Most rare diseases have unknown etiologies and are difficult to cure, often requiring lifelong management and prolonged care. Consequently, they impose substantial psychosocial [1,2] and economic burdens [3,4] on affected individuals and their families, along with considerable societal costs. Globally, more than 7,000 rare diseases have been identified, affecting an estimated 300 million people [5]. However, due to a lack of specialists and infrastructure, even basic epidemiological data, such as accurate incidence and prevalence rates, remain insufficient for most rare diseases [6].

Definitions of rare diseases vary across countries. The European Union (EU) defines them as conditions affecting fewer than 50 individuals per 100,000 people, while the United States categorizes them as diseases affecting fewer than 200,000 individuals nationwide. In Japan, rare diseases are defined as diseases with unknown pathogenic mechanisms and no established treatments. Australia considers diseases rare if they affect fewer than 2,000 individuals, regardless of curability [7]. In Korea, rare diseases are defined as conditions affecting fewer than 20,000 individuals, or where the number of patients is unknown due to diagnostic difficulty. Additionally, ultra-rare diseases refer to those with specific diagnostic criteria and either fewer than 200 affected individuals or no designated Korean Standard Classification of Diseases (KCD) code. Newly identified chromosomal abnormalities are also included under rare diseases if they lack a specific KCD code and can be classified as diseases rather than symptoms [8].

The enactment of the Rare Disease Management Act in December 2015 established an official definition of rare diseases in Korea and led to the creation of a nationally managed list. This laid the foundation for statistical evaluation and policy development [6]. Within this framework, a registration and monitoring program was launched, resulting in the annual publication of the annual report on the rare disease patients in Korea. This report provides essential data on incidence (newly registered patients), mortality, and healthcare utilization [8]. However, systematic studies on the prevalence of rare diseases remain limited both domestically and internationally. One of the few resources available is the Orphanet database, coordinated by the French National Institute of Health and Medical Research (INSERM) and involving 40 European countries [9].

This study was prompted by the establishment of the Jeju Regional Center for Rare Diseases in February 2021 [10] and addressed the urgent need to investigate the epidemiological landscape of rare diseases in the region. The primary objective of this study was to generate foundational data on the prevalence of rare diseases in Jeju, thereby contributing to evidence-based policymaking.

METHODS

1. Customized research database from the National Health Insurance Service

This study used the customized research database provided by the National Health Insurance Service (NHIS) of Korea (NHIS-2023-1-485). The study population included patients with a registered address in Jeju Special Self-Governing Province who had outpatient or inpatient visits for any of the designated rare diseases between January 1 and December 31, 2021. Healthcare utilization data included all the outpatient and inpatient claims related to all rare diseases.

The list of all rare diseases used in this study was obtained from table 4 (Designated Rare Diseases for the Co-payment Reduction Program) of the Ministry of Health and Welfare (MOHW) notification No. 2021-170, which took effect on July 1, 2021 [11]. Specifically, it included rare diseases (except for ultra-rare diseases and other chromosomal abnormalities), ultra-rare diseases, and other chromosomal abnormalities.

2. Crude prevalence rate

The crude prevalence rate was calculated by dividing the total number of patients (cases) with diseases by the mid-year registered population of Jeju Special Self-Governing Province in 2021 (denominator population), based on data from the Korean Statistical Information Service (http://kosis.kr/). The population was stratified according to sex and grouped into 5-year age intervals.

The crude prevalence rate was expressed per 100,000 people. The formula [12] used was as follows: crude prevalence rate (per 100,000)=(number of patients with rare diseases÷mid-year population)×100,000.

3. Hereditary status

Classification of hereditary and non-hereditary diseases was based on the list provided by the Jeju Regional Center for Rare Diseases (Supplementary Material 1).

4. Prevalence of diseases

To assess the prevalence status of rare diseases in Jeju, the number of rare diseases was determined using four complementary approaches. First, the total number of rare diseases officially designated for co-payment reduction by the MOHW was identified, based on the list officially announced as of July 1, 2021 [11].

Second, the number of rare diseases identified within the customized database provided by the NHIS was obtained based on the diagnostic codes recorded between January 1 and December 31, 2021.

Third, the number of rare diseases observed among patients residing in Jeju during the study year was calculated. This included diseases for which at least one patient with a Jeju address received outpatient or inpatient care in 2021, as recorded in the primary or secondary diagnosis fields, using a combination of rare disease exemption codes and corresponding disease codes based on the 2021 designation.

Finally, the number of rare diseases with no identified patients in Jeju in 2021 was calculated by subtracting the number of observed rare diseases from the total number of designated rare diseases.

To ensure consistency in reporting, each rare disease was determined based on an operational rule. Specifically, one rare disease was defined as a unique pair consisting of a single designated rare disease exemption code (Special Case Exemption Code) and a single corresponding KCD code in accordance with the list of rare diseases officially announced by the MOHW.

5. Statistical analyses

Descriptive statistics were used to summarize the data, including frequencies and proportions, stratified by sex and age. Data processing and analysis were performed using Interactive SQL and the SAS Enterprise Guide version 4.3 (SAS Institute, Cary, NC, USA).

This study was approved by the Institutional Review Board of Jeju University Hospital (JEJUNUH2023-01-002). The requirement for informed consent was waived.

RESULTS

1. Number of patients with all rare diseases (cases) and claims

1) Comparison by sex and age in Jeju

Among the 4,669 patients with rare diseases, 2,083 (44.6%) were male and 2,586 (55.4%) were female. In adults aged 19 years and older, there were 1,753 males and 2,339 females, with a male-to-female ratio of 100:133, indicating a higher crude prevalence rate in females. In contrast, among children aged 18 years and younger, there were 330 males and 247 females, with a male-to-female ratio of 134:100 (equivalent to 100.0:74.8), showing a higher crude prevalence rate in males.

Regarding the total number of insurance claims (n=40,219), males filed 17,690 (44.0%) claims and females filed 22,529 (56.0%) claims. Among adults, males filed 13,214 claims and females filed 18,593 claims, resulting in a male-to-female ratio of 100.0:140.7. However, among children, males filed 4,476 claims and females filed 3,936 claims, with a male-to-female ratio of 114:100 (equivalent to 100.0:87.9), again indicating a higher rate among males (Table 1).

2) Comparison by eligibility type, age, and sex in Jeju

Among patients with all rare diseases, 284 (6.1%) were covered by medical aid, accounting for 2,402 claims (6.0% of all claims). Sex distribution among medical aid beneficiaries showed patterns similar to those observed in the overall population in both adult and pediatric groups. Specifically, Medical Aid recipients constituted 260/4,092 (6.4%) of adult patients and 24/577 (4.2%) of pediatric patients. Regarding claims, 2,195/31,807 (6.9%) of adult claims and 207/8,412 (2.5%) of pediatric claims were from medical aid beneficiaries, indicating that the proportion was higher among adults than among children (Table 2).

2. Crude prevalence rate

1) Crude prevalence rate of all rare diseases by age and sex in Jeju

The overall crude prevalence rate of all rare diseases in Jeju was 696 cases per 100,000 people, with 619 per 100,000 among males and 774 per 100,000 among females. When categorized into 5-year age intervals, the age-specific crude prevalence rate ranged from a minimum of 458 per 100,000 in the 0-4 age group to a maximum of 1,441 per 100,000 in the 75-79 age group. Notably, individuals aged 65-89 years showed relatively higher crude prevalence rates than other age groups, ranging from 1,221 to 1,441 per 100,000 people (Table 3).

2) Crude prevalence rate of hereditary and non-hereditary rare diseases by age and sex in Jeju

Among all rare diseases, the crude prevalence rate of hereditary diseases was 130 per 100,000 people, while that of non-hereditary diseases was 575 per 100,000 people, resulting in a ratio of 18:82 between hereditary and non-hereditary diseases. The proportion of hereditary diseases differed markedly between age groups: hereditary diseases accounted for 643/4,137 (15.5%) of adult patients compared to 226/593 (38.1%) of pediatric patients, which was more than twice the proportion observed in adults (Table 4). In this study, patients aged 18 years or younger were classified as pediatric patients and those aged 19 years or older were classified as adult patients. The number of patients and diseases was reported based on this classification. However, in Table 4, the population data from the national statistics, grouped in 5-year intervals, were used, resulting in the pediatric group being defined as up to 19 years of age, which caused a slight discrepancy.

3) Crude prevalence rate of top and bottom ranked rare diseases in Jeju

The crude prevalence rate of the top 30 most frequent rare diseases (except for ultra-rare diseases and other chromosomal abnormalities) in Jeju ranged from 51 to 4 cases per 100,000 people. Among these, 16 diseases had a crude prevalence rate of 10 or more per 100,000 people (Supplementary Table 1).

Notably, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was previously classified as an ultra-rare disease (assigned the Special Case Exemption Code V900 under the rare disease benefit program) in 2020 but was reclassified as a rare disease in 2021. However, in the 2021 claim data used for analysis, two cases were recorded under the previous 2020 classification code. The crude prevalence rate of CADASIL was calculated as 14 per 100,000 people, based on 96 identified cases among 670,993 individuals.

The 10 most common rare diseases in Jeju were systemic lupus erythematosus with organ or system involvement (crude prevalence rate of 51), idiopathic dilated cardiomyopathy (crude prevalence rate of 45), non-obstructive hypertrophic cardiomyopathy (crude prevalence rate of 32), Sjögren's syndrome with myopathy (crude prevalence rate of 31), moyamoya disease (crude prevalence rate of 30), idiopathic pulmonary fibrosis (crude prevalence rate of 27), Behçet's disease (crude prevalence rate of 24), retinitis pigmentosa (crude prevalence rate of 15), CADASIL (crude prevalence rate of 14), and bicuspid aortic valve (crude prevalence rate of 13) (Supplementary Fig. 1).

Among the 248 rare diseases reported in 2021 among patients in the Jeju region, 56 were identified in only a single case. These diseases ranked 193 or below in the frequency distribution. The names of these single-occurrence diseases are presented in Supplementary Table 2.

4) Proportion of cases by system classification in Jeju

When classifying all rare diseases by system, based on the major categories of KCD, the most common categories were musculoskeletal system and connective tissue at 24.2%, followed by circulatory system at 18.5%, congenital malformations, deformations, and chromosomal abnormalities at 14.2%, and nervous system at 14.1%. Categories with a proportion of less than 5.0% included genitourinary system, skin and subcutaneous tissue, mental and behavioral disorders, eyes and ears, and respiratory system.

In the pediatric population, rare diseases were most prominently classified as congenital malformations, deformations, or chromosomal abnormalities, which account for 57% of all pediatric rare diseases. This notably high proportion distinguished the pediatric group from the adult group. The next most common categories were nervous system at 11% and musculoskeletal system and connective tissue at 10% (Fig. 1).

3. Prevalent diseases in Jeju

1) All designated vs. observed rare diseases: the MOHW notification on July 1, 2021, and the NHIS data in 2021

As of July 1, 2021, 1,201 diseases were designated under the rare disease benefit program of the MOHW. Of these, 898 (74.8%) were classified as rare diseases (except for ultra-rare diseases and other chromosomal abnormalities), 249 (20.7%) as ultra-rare diseases, and 54 (4.5%) as other chromosomal abnormalities. In comparison, analysis of the 2021 NHIS claims data identified 640 rare diseases, including 470 (73.4%) rare diseases (except for ultra-rare diseases and other chromosomal abnormalities), 161 (25.2%) ultra-rare diseases, and nine (1.4%) chromosomal abnormalities (Table 5).

2) All prevalent rare diseases in Jeju

Among Jeju residents, 279 rare diseases were identified based on data for patient claims. Of these, 249 (89.2%) were classified as rare diseases (except for ultra-rare diseases and other chromosomal abnormalities), 29 (10.4%) as ultra-rare diseases, and one (0.4%) as other chromosomal abnormalities.

Based on the NHIS claims data, the proportion of rare diseases with at least one patient identified among Jeju residents in 2021 was approximately 44% of all rare diseases recorded nationwide. When analyzed by classification, this proportion was 53% for rare diseases, 18% for ultra-rare dis eases, and 11% for other chromosomal abnormalities (Table 5).

3) Multiple rare disease diagnoses in Jeju

Among patients with rare diseases, excluding ultra-rare diseases and other chromosomal abnormalities (n=4,645), 382 (8.3%) patients had multiple rare disease diagnoses. The proportion was markedly higher among patients with ultra-rare diseases at 9 out of 36 (25.0%). However, the maximum number of diagnoses per patient was four among those with rare diseases (except for ultra-rare diseases and other chromosomal abnormalities) and three among those with ultra-rare diseases (Table 6).

DISCUSSION

This is the first population-based study to examine the prevalence of all rare diseases in Jeju using data from the customized database provided by the NHIS. We estimated the total number of patients diagnosed with rare diseases and identified 4,669 cases in 2021. Of these, 2,083 (44.6%) were male and 2,586 (55.4%) were female. In adults (≥19 years), females showed a higher crude prevalence rate (male-to-female ratio, 100:133), whereas in children (≤18 years), males were more prevalent (134:100). We estimated that the crude prevalence rate of all rare diseases in Jeju was 696 cases per 100,000 people, with 619 per 100,000 among males and 774 per 100,000 among females in 2021.

Although several studies in Korea have reported the prevalence of specific rare diseases [13-16], this is the first study to examine the overall prevalence of all rare diseases within a defined region. The lack of comparable studies makes it difficult to assess the relative significance of our findings. Nevertheless, this study offers meaningful empirical data that the Jeju Regional Center for Rare Diseases mandates to monitor and utilize.

This study did not include clinical diagnostic criteria or detailed disease characteristics, which may raise concerns regarding the potential misclassification of diagnoses. However, as this study used rare disease exemption codes designated through the national program, it is likely that diagnostic accuracy was relatively high, supporting the reliability of the results. Nevertheless, the study only included patients who were registered in the co-payment reduction program; therefore, it is possible that some cases were not captured, leading to an underestimation of the actual prevalence [8].

While the co-payment reduction program offers financial benefits that generally encourage accurate disease coding, there may still be instances in which rare diseases are under-coded. This could occur due to delays in receiving a confirmed diagnosis, administrative mistakes, or incomplete documentation in clinical records. Therefore, even with the use of exemption codes, the possibility of under-coding cannot be completely excluded.

Beyond the data-related limitations, this study highlights a critical aspect of patient vulnerability, namely the socioeconomic disadvantage of individuals living with rare diseases. In this study, the proportion of patients with rare diseases receiving medical aid was 6.0%, much higher than the proportion of recipients of National Basic Livelihood Security (30,634/670,992, 4.6%) in Jeju in the same year [17]. This proportion was 4.2% among children and 6.4% among adults, indicating a higher level of economic vulnerability in the adult population. These findings suggest that individuals with rare diseases may be more economically disadvantaged than the general population and that this vulnerability becomes more pronounced with age in Jeju.

Previous national statistics from 2019 to 2022 consistently reported that the proportion of male patients with newly diagnosed rare diseases was slightly higher than that of female patients [18-22]. In contrast, our analysis, which focused on prevalence, showed that the overall proportion of female patients was higher. Male patients were more common only among individuals aged 18 years or younger. This difference may reflect the cumulative nature of the prevalence data, which include all existing patients rather than just new cases, and may be influenced by differences in survival rates and other epidemiological factors. It may also be partly explained by the slightly higher number of male births in Korea compared with female births (105.0 in 2024) [23].

The discrepancy between the number of rare diseases listed in the MOHW notification and those identified in the NHIS data is mainly due to structural differences in classification and data recording systems. The number of officially announced diseases by the MOHW tends to increase annually (926 diseases in 2019 [17], 1,014 in 2020 [18,19], 1,086 in 2021 [20], and 1,123 in 2022 [21]) and includes conditions that are differentiated by assigning additional serial numbers to a single disease code [8]. However, the NHIS dataset does not include these serial numbers, resulting in multiple rare diseases sharing a single disease code. Moreover, ultra-rare diseases are grouped under the exemption code V900; however, some share one code among several conditions, whereas others are represented by multiple codes per disease. In certain cases, especially those classified under the syndrome classification guideline, the absence of a specific disease code makes identification impossible. These system-level characteristics explain the substantial discrepancy in the number of all rare diseases recognized by the two sources.

Interestingly, despite the difference in the total disease counts, the proportional distribution of rare diseases (except for ultra-rare diseases and other chromosomal abnormalities), ultra-rare diseases, and other chromosomal abnormalities was similar in both datasets, at approximately 75%, 25%, and less than 5%, respectively (Table 5). However, when comparing the rare diseases identifiable in the NHIS data with those observed in Jeju, differences were noted in the proportion of disease types. While the NHIS data showed a composition of approximately 73% of rare diseases, 25% of ultra-rare diseases, and 1% of other chromosomal abnormalities, the corresponding proportions in Jeju were 89%, 10%, and 0%, respectively. This suggests that the rarer the disease, the less likely it is to be represented in Jeju, likely due to the region’s small population, which accounts for only 1.3% of the national population. Therefore, the prevalence of extremely rare diseases in Jeju may be disproportionately lower than in larger regions on the mainland.

Among the identifiable rare diseases in the NHIS data, the proportion of diseases with at least one case in Jeju in 2021 was approximately 44%. Specifically, the proportions were 53% for rare diseases (excluding ultra-rare diseases and other chromosomal abnormalities), 18% for ultra-rare diseases, and 11% for other chromosomal abnormalities (Table 5). These findings suggest that the rarer the disease, the smaller its observed patient population, reflecting the challenges of detecting ultra-rare conditions in smaller regional populations.

Some patients were diagnosed with more than one rare disease, leading to the total number of prevalent cases by disease (Table 6) slightly exceeding the total number of individual patients with rare diseases (Tables 1, 2). This distinction is important when interpreting disease-specific prevalence, as it prevents an overestimation of the affected population.

This study had some inherent limitations. The analysis was based on the NHIS claims data [24], which are primarily collected for administrative and reimbursement purposes rather than research. Therefore, the potential for misclassification, diagnostic inaccuracies, and under-coding cannot be excluded, particularly for rare or underdiagnosed conditions. Despite these limitations, repeated prevalence surveys are a practical approach to monitor trends and guide policies for rare diseases, especially when conducted using population-level datasets [25]. Future studies should incorporate healthcare utilization and cost analysis to better inform evidence-based policies and resource allocation.

By utilizing the NHIS database and developing a systematic classification framework for the prevalence status, this study quantitatively analyzed the prevalence of rare diseases at the regional level. Based on this foundation, future research should include other regions and multicenter comparisons to validate and generalize the findings of this study. Furthermore, repeated prevalence studies within specific regions are necessary to monitor trends over time.

The findings of this study provide critical baseline data that can inform region-specific public health strategies for the management of rare diseases. Identifying local prevalence patterns by age, sex, and disease type allows policy-makers to prioritize resource allocation, enhance early diagnosis programs, and design tailored patient support services.

Compared to previous national reports (annual reports on patients with rare diseases) in Korea, which primarily focused on newly registered patients with rare diseases, this study analyzed the overall prevalence of rare diseases among all the registered patients, thereby offering a broader understanding of the regional burden of rare diseases. International efforts, such as Orphanet, have emphasized the necessity of region-specific surveillance of rare diseases, and our findings align with the growing need for localized epidemiological assessments to guide policy development.

In addition to the general limitations of the administrative data, the rare disease registration system (co-payment reduction program) presents structural limitations that may have resulted in an underestimation of the true prevalence reported in this study. Patients who have not received a diagnosis or who fail to complete mandatory re-registration every five years may be missed. Moreover, inaccuracies in disease coding within administrative datasets cannot be entirely ruled out.

This study is the first to report the overall crude prevalence rate of rare diseases in the Jeju region using a customized research database from the NHIS. The findings revealed the regional characteristics in prevalence by sex, age, and eligibility type. Due to Jeju’s small population size, the rarer the disease, the less likely it is to be observed. These findings provide important baseline data for regional surveillance of rare diseases and policy planning. Moreover, they underscore the importance of region-specific surveillance and can serve as a cornerstone for tailoring rare disease management strategies in geographically distinct populations, such as Jeju.

Supplementary Material

Supplementary Material 1.

jmls-2025-22-2-69-Supplementary-Material-1.xlsx

Supplementary Table 1.

Crude prevalence rate of the top 30 most frequent rare diseases except for ultra-rare diseases and other chromosomal abnormalities in the Jeju (2021)

jmls-2025-22-2-69-Supplementary-Table-1.pdf

Supplementary Table 2.

Single-case rare diseases except for ultra-rare diseases and other chromosomal abnormalities in Jeju (2021)

jmls-2025-22-2-69-Supplementary-Table-2.pdf

Supplementary Figure 1.

The 10 most common rare diseases in Jeju (2021).

jmls-2025-22-2-69-Supplementary-Fig-1.pdf

Notes

ACKNOWLEDGEMENTS

This study was part of a policy research project commissioned by the Korea Disease Control and Prevention Agency (KDCA), titled A Survey on Rare Diseases in the Jeju Region and Proposal of a Regionalized Model for Specialized Centers (Project No. 202203134B5-00). We would like to express our sincere gratitude to the Division of Rare Disease Management, Department of Chronic Disease Prevention and Control, KDCA and the NHIS for providing access to the customized research database (NHIS-2023-1-485) used in this analysis.

CONFLICT OF INTEREST

The author reports no conflict of interest.

FUNDING

None.

Figure 1.

Prevalence and proportion of cases by system classification in Jeju (2021) and comparison between children and adults.

Table 1.

Number of patients with all rare diseases (cases) and claims by sex and age in Jeju (2021)

Sex	Case			Claims
Sex	Adults (19≤)	Children (18≥)	Total	Adults (19≤)	Children (18≥)	Total
Male	1,753 (37.5)	330 (7.1)	2,083 (44.6)	13,214 (32.9)	4,476 (11.1)	17,690 (44.0)
Female	2,339 (50.1)	247 (5.3)	2,586 (55.4)	18,593 (46.2)	3,936 (9.8)	22,529 (56.0)
Total			4,669 (100.0)			40,219 (100.0)

Values are presented as frequency (%).

Table 2.

Number of patients with all rare diseases and claims by the National Health Insurance’s eligibility type, age, and sex in Jeju (2021)

Category	Case					Claims
	Adults (19≤)		Children (18≥)			Adults (19≤)		Children (18≥)
	Male	Female	Male	Female	Total	Male	Female	Male	Female	Total
NHI enrollees	1,639 (35.1)	2,193 (47.0)	316 (6.8)	237 (5.1)	4,385 (94.0)	12,135 (30.2)	17,477 (43.5)	4,358 (10.8)	3,847 (9.6)	37,817 (94.0)
Medical aid beneficiaries	114 (2.4)	146 (3.1)	14 (0.3)	10 (0.2)	284 (6.0)	1,079 (2.7)	1,116 (2.8)	118 (0.3)	89 (0.2)	2,402 (6.0)
Subtotal	4,092 (87.6)		577 (12.4)			31,807 (79.1)		8,412 (20.9)
Total			4,669 (100.0)					40,219 (100.0)

Values are presented as frequency (%).

NHI: National Health Insurance.

Table 3.

Crude prevalence rate of all rare diseases by age and sex in Jeju (2021)

Age group	Number of populations			Cases			Crude prevalence rate (cases/100,000)
Age group	Male	Female	Total	Male	Female	Total	Male	Female	Total
0-4	12,345	11,683	24,028	55	55	110	446	471	458
5-9	18,015	17,076	35,090	86	75	161	477	439	459
10-14	18,581	17,311	35,892	95	62	157	511	358	437
15-19	18,264	16,287	34,551	118	68	186	646	418	538
20-24	21,510	18,989	40,498	118	92	210	549	485	519
25-29	21,610	19,490	41,100	108	87	195	500	446	474
30-34	18,057	17,471	35,527	82	102	184	454	584	518
35-39	22,954	22,892	45,846	87	132	219	379	577	478
40-44	26,709	25,948	52,657	118	156	274	442	601	520
45-49	30,313	27,982	58,294	135	204	339	445	729	582
50-54	30,981	28,509	59,489	146	232	378	471	814	635
55-59	27,476	25,453	52,928	164	249	413	597	978	780
60-64	24,158	23,749	47,906	195	257	452	807	1,082	944
65-69	16,279	17,043	33,322	170	237	407	1,044	1,391	1,221
70-74	11,833	13,365	25,198	150	195	345	1,268	1,459	1,369
75-79	8,771	11,285	20,056	130	159	289	1,482	1,409	1,441
80-84	5,660	9,642	15,302	81	124	205	1,431	1,286	1,340
85-89	2,555	6,528	9,083	38	77	115	1,488	1,180	1,266
More than 90	613	3,615	4,228	7	23	30	1,142	636	710
Total	336,680	334,313	670,993	2,083	2,586	4,669	619	774	696

Table 4.

Crude prevalence rate of hereditary and non-hereditary rare diseases except for ultra-rare diseases and other chromosomal abnormalities by age and sex in Jeju (2021)

Age group	Number of populations			Hereditary						Non-hereditary
				Cases			Crude prevalence rate (cases/100,000)			Cases			Crude prevalence rate (cases/100,000)
	Male	Female	Total	Male	Female	Total	Male	Female	Total	Male	Female	Total	Male	Female	Total
0-4	12,345	11,683	24,028	20	17	37	162	146	154	41	78	78	332	668	325
5-9	18,015	17,076	35,090	34	34	68	189	199	194	42	96	96	233	562	274
10-14	18,581	17,311	35,892	44	26	70	237	150	195	38	92	92	205	531	256
15-19	18,264	16,287	34,551	37	24	61	203	147	177	46	127	127	252	780	368
20-24	21,510	18,989	40,498	42	22	64	195	116	158	70	150	150	325	790	370
25-29	21,610	19,490	41,100	26	16	42	120	82	102	73	156	156	338	800	380
30-34	18,057	17,471	35,527	24	16	40	133	92	113	88	146	146	487	836	411
35-39	22,954	22,892	45,846	15	17	32	65	74	70	117	191	191	510	834	417
40-44	26,709	25,948	52,657	23	21	44	86	81	84	137	233	233	513	898	442
45-49	30,313	27,982	58,294	23	31	54	76	111	93	174	286	286	574	1,022	491
50-54	30,981	28,509	59,489	17	26	43	55	91	72	208	339	339	671	1,189	570
55-59	27,476	25,453	52,928	35	27	62	127	106	117	224	355	355	815	1,395	671
60-64	24,158	23,749	47,906	33	30	63	137	126	132	231	395	395	956	1,663	825
65-69	16,279	17,043	33,322	28	32	60	172	188	180	209	355	355	1,284	2,083	1,065
70-74	11,833	13,365	25,198	22	25	47	186	187	187	171	300	300	1,445	2,245	1,191
75-79	8,771	11,285	20,056	14	21	35	160	186	175	141	257	257	1,608	2,277	1,281
80-84	5,660	9,642	15,302	12	20	32	212	207	209	104	173	173	1,837	1,794	1,131
85-89	2,555	6,528	9,083	4	9	13	157	138	143	69	103	103	2,701	1,578	1,134
More than 90	613	3,615	4,228	-	2	2	-	55	47	21	28	28	3,426	775	662
Total	336,680	334,313	670,993	453	416	869	135	124	130	2,204	3,860	3,860	655	1,155	575

Table 5.

Numbers of all rare diseases in Jeju (2021)

Category	Officially announced Diseases by KDCA^*	Number of all rare diseases from NHIS
Category	Officially announced Diseases by KDCA^*	Diseases	Diseases with reported cases in Jeju	Diseases without reported cases in Jeju	Ratio^† (%)
All rare diseases	1,201 (100)	640 (100)	279 (100)	361 (100)	44
Rare diseases except for ultra-rare diseases and other chromosomal abnormalities	898 (75)	470 (73)	249 (89)	221 (61)	53
Ultra-rare diseases	249 (21)	161 (25)	29 (10)	132 (37)	18
Other chromosomal abnormalities	54 (4)	9 (1)	1 (0)	8 (2)	11

Values are presented as frequency (%).

NHIS: National Health Insurance Service, KDCA: Korea Disease Control and Prevention Agency.

^* As specified in Table 4 of the Ministry of Health and Welfare notification No. 2021-170, which lists rare diseases eligible for the co-payment reduction program,

^† Number of diseases observed in Jeju/total number of diseases in NHISS.

Table 6.

Multiplicity of diagnosis and proportion of patients with multiple rare disease diagnoses in Jeju (2021)

Multiplicity of diagnosis	Diagnosis count	Rare diseases except for ultra-rare diseases and other chromosomal abnormalities	Ultra-rare diseases
No	1	4,263 (91.8)	27 (75.0)
Yes	2	342 (7.4)	8 (22.2)
Yes	3	36 (0.8)	1 (2.8)
Yes	4	4 (0.1)	NA
Total		4,645 (100.0)	36 (100.0)

Values are presented as frequency (%).

NA: not applicable.

REFERENCES

1. Walkowiak D, Domaradzki J. Perception of psychosocial burden in mothers of children with rare pediatric neurological diseases. Sci Rep 2025;15:6295.

2. Atkins JC, Padgett CR. Living with a rare disease: psychosocial impacts for parents and family members - a systematic review. J Child Fam Stud 2024;33:617-36.

3. Angelis A, Tordrup D, Kanavos P. Socio-economic burden of rare diseases: a systematic review of cost of illness evidence. Health Policy 2015;119:964-79.

4. Sequeira AR, Mentzakis E, Archangelidi O, Paolucci F. The economic and health impact of rare diseases: a meta-analysis. Health Policy Technol 2021;10:32-44.

5. The Lancet Global Health. The landscape for rare diseases in 2024. Lancet Glob Health 2024;12:e341.

6. Choi EK, Lee J. Key findings from 2019 annual report on rare disease patients in Korea. Public Health Wkly Rep 2021;14:2025-36.

7. Ahn YJ. Domestic and international rare disease policies and research trends. Daejeon: BioINpro; c2020 [cited 2024 Jun 25]. Available from: https://www.bioin.or.kr/board.do?num=300917&cmd=view&bid=report.

8. Lee K, Lee TH, Park IS, Kim JY, Sung JH, Choi KH. Current status of statistics and future improvement plans on rare diseases in Korea - focusing on 2021 annual report on the rare disease patients in Korea -. Public Health Wkly Rep 2024;17:1635-53.

9. INSERM. Prevalence and incidence of rare diseases: bibliographic data prevalence, incidence or number of published cases listed by diseases (in alphabetical order) [Internet]. Paris: Orphanet; c2024 [cited 2025 Mar 31]. Available from: https://www.orpha.net/pdfs/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf.

10. Jeju Regional Center for Rare Diseases. Introduction to the Jeju Regional Center for Rare Diseases [Internet]. Jeju: Jeju National University Hospital; c2021 [cited 2025 Mar 31]. Available from: https://www.jejunuh.co.kr/specialcenter/rare-disease/introduction/intro/_/view.do.

11. Ministry of Health and Welfare. Criteria for the Co-payment Reduction Program [Internet]. Sejong: Ministry of Government Legislation Korean Law Information Center; c2022 [cited 2025 Apr 3]. Available from: https://law.go.kr/LSW/admRulLsInfoP.do?admRulSeq=2100000211826.

12. Yoo KY. Categorical data analysis for medical and health research. Seoul: Seoul National University Press; 1996.

13. Lee HL, Kim JY, Seok JM, Hong YH, Lim NG, Shin HY, et al. Prevalence and incidence of neuromyelitis optica spectrum disorder in Korea: population based study. J Korean Med Sci 2020;35:e115.

14. Seo SR, Jang SY, Lee GY, Choi B, Chun H, Cho EJ, et al. Prevalence of amyloidosis in Korea. Orphanet J Rare Dis 2017;12:1-5.

15. Lim J, Kim HJ. Epidemiology of autoimmune liver disease in Korea: evidence from a nationwide real-world database. Orphanet J Rare Dis 2024;19:178.

16. Yoon HY, Kim HM, Kim YJ, Song JW. Prevalence and incidence of sarcoidosis in Korea: a nationwide population-based study. Respir Res 2018;19:1-8.

17. Ministry of the Interior and Safety. Resident registration-based population statistics [Internet]. Daejeon: Statistics Korea; c2023 [cited 2024 Mar 4]. Available from: https://kosis.kr/statHtml/statHtml.do?orgId=101&tblId=DT_1B040B3&conn_path=I2.

18. Korea Disease Control and Prevention Agency (KDCA). 2019 annual report on the rare disease patients in Korea [Internet]. Cheongju: KDCA; c2023 [cited 2025 Apr 3]. Available from: https://helpline.kdca.go.kr/cdchelp/ph/ptlcontents/selectPtlConSent.do?schSno=145&menu=C0400.

19. Korea Disease Control and Prevention Agency (KDCA). 2020 annual report on the rare disease patients in Korea [Internet]. Cheongju: KDCA; c2023 [cited 2025 Apr 3]. Available from: https://helpline.kdca.go.kr/cdchelp/ph/ptlcontents/selectPtlConSent.do?schSno=145&menu=C0400.

20. Korea Disease Control and Prevention Agency (KDCA). 2020 annual report on the rare disease patients in Korea (2) [Internet]. Cheongju: KDCA; c2023 [cited 2025 Apr 3]. Available from: https://helpline.kdca.go.kr/cdchelp/ph/ptlcontents/selectPtlConSent.do?schSno=145&menu=C0400.

21. Korea Disease Control and Prevention Agency (KDCA). 2021 annual report on the rare disease patients in Korea [Internet]. Cheongju: KDCA; c2023 [cited 2025 Apr 3]. Available from: https://helpline.kdca.go.kr/cdchelp/ph/ptlcontents/selectPtlConSent. do?schSno=145&menu=C0400.

22. Korea Disease Control and Prevention Agency (KDCA). 2022 annual report on the rare disease patients in Korea [Internet]. Cheongju: KDCA; c2023 [cited 2025 Apr 3]. Available from: https://helpline.kdca.go.kr/cdchelp/ph/ptlcontents/selectPtlConSent.do?schSno=145&menu=C0400.

23. Ministry of the Interior and Safety. Sex ratio at birth [Internet]. Daejeon: Statistics Korea; c2023 [cited 2024 Apr 3]. Available from: https://kosis.kr/statHtml/statHtml.do?orgId=101&tblId=DT_1B040A3&conn_path=I2.

24. Nathan H, Pawlik TM. Limitations of claims and registry data in surgical oncology research. Ann Surg Oncol 2008;15:415-23.

25. French GL, Cheng AF, Wong SL, Donnan S. Repeated prevalence surveys for monitoring effectiveness of hospital infection control. Lancet 1989;2:1021-3.