Five-year Incidence Trends and the Status of Major Rare Diseases in 2023 in the 「Annual Report on the Rare Disease Patients in Korea」

Abstract

Objectives

This study analyzed 5-year trends in rare disease incidence, deaths, and medical expenditures in the Republic of Korea using the 「Annual Report on the Rare Disease Patients in Korea」 (the Annual Report), with particular attention to the 2023 incidence figures by age, province, and frequently occurring diseases.

Methods

This retrospective descriptive study used data from the Annual Report from 2019 to 2023. The annual numbers of newly registered rare disease cases and of deaths and the figures for healthcare utilization were analyzed, with particular attention to the incidence status in 2023.

Results

Newly registered rare disease cases remained at around 50,000 annually before rising to 62,420 in 2023, with deaths and medical expenditures also increasing. In 2023, the incidence was highest among individuals in their 60s and those in the Gyeonggi-do region. Idiopathic pulmonary fibrosis and systemic lupus erythematosus with organ or system involvement were the most common rare diseases among males and females, respectively. Crohn’s disease of the small and large intestine was the most frequent among those in their 10s and 20s, autosomal dominant polycystic kidney disease among those in their 30s to 50s, and idiopathic pulmonary fibrosis among those aged 60 and older, which last also incurred the highest total annual medical expenditure.

Conclusions

The Annual Report has enhanced analytical accuracy and comprehensiveness through data refinement and statistical expansion. Future efforts should be directed to a transition from incidence-centered statistics to the establishment of a longitudinal data infrastructure that records incidence rates, survival rates, and the overall prevalence of rare diseases.

Key messages

① What is known previously?

Five editions of the 「Annual Report on the Rare Disease Patients in Korea」 have been published. Until 2022, the number of new rare disease cases remained around 50,000.

② What new information is presented?

In 2023, the number of new rare disease cases was found to be 62,420, of which idiopathic pulmonary fibrosis accounted for the largest share of both the number of cases and total annual medical expenditures, followed by the newly designated polycystic kidney disease, autosomal dominant.

③ What are implications?

Expansions of the rare disease list and advances in statistics successfully steered potential patients into the healthcare system, indicating that future policies should tailor the statistical framework to disease characteristics.

Introduction

Globally, an estimated 300 to 400 million people are affected by rare diseases, and this number is increasing as new rare diseases are being continuously identified [1]. However, for each individual rare disease, the number of patients is small; therefore, the pathophysiology of such diseases has not been clearly elucidated, and the patterns of manifestation of such diseases are diverse, often making them highly unpredictable [2,3]. Previous studies have reported that it takes an average of more than 5 years to receive a definitive diagnosis for a rare disease, and even after diagnosis, patients face challenges because 95% of these diseases have no approved treatments [4,5]. Although diagnosis rates are gradually improving with advancements in medical technology, patients also face economic difficulties and multidimensional unmet needs due to the burden of medical expenses from high treatment costs and the accumulation of caregiving costs [6]. For these reasons, although rare diseases are a public health area requiring systematic management at the national level, most research on rare diseases is primarily based on small target populations focused on specific diseases, which limits the ability to identify longitudinal changes and trends in healthcare utilization patterns for all rare diseases nationwide [7,8].

To overcome these limitations and establish a foundation for evidence-based policy-making, the Korean government has been publishing the 「Annual Report on the Rare Disease Patients in the Korea」 (the Annual Report) since 2020, which systematically links data dispersed across various administrative and public institutions [9-13]. The Annual Report has policy and academic value in that it annually presents the number of incident cases of rare diseases by sex, region, and age, the number of deaths occurring in the same year among the incident cases for that year, and healthcare utilization status during the one-year period following registration for the Special Copayment Reduction Program for Rare Diseases. Due to the low prevalence and clinical diversity of rare diseases, it is difficult to bridge the gap between patients’ actual healthcare and welfare needs and support policies [14-16]. This phenomenon might be attributed to the small number of patients, which makes it difficult to provide sufficient quantitative evidence for policy-making, and the different clinical characteristics of each disease, which may create constraints within a generalized support system. Therefore, to incorporate patients’ multidimensional needs into policy, it is necessary to refine the national statistical system and provide empirical data.

Over the past 5 years, the compilation method for the Annual Report has been continuously refined to enhance the precision and inclusivity of the data. The 2019 Annual Report presented only the number of incident cases for that year on a limited basis, while the mortality status of the 2019 incident cases and their healthcare utilization during the first 3 months after registration were linked and published in the following year’s 2020 Annual Report due to the data follow-up period. Consequently, concerns were raised that this transitional approach, which resulted in the inclusion of statistics from different years (2020 incidence statistics and 2019 mortality and healthcare utilization statistics) within a single annual report, could undermine the timeliness and utility of the data and lead to confusion in interpretation. To address this structural limitation, the generation of 2021 incidence statistics was temporarily suspended. Instead, the number of 2020 incident cases was recalculated, and their mortality and 3-month healthcare utilization were analyzed, leading to the publication of the 2020 Annual Report (2) in 2022. Subsequently, starting with the 2021 Annual Report published in 2023, the collection and follow-up period for administrative data was extended from the previous 1 to 2 years and established as standard practice. This approach established a stable system for integrating statistics on incident cases, mortality, and healthcare utilization for a given year within a single annual report. As the data follow-up period was extended to 2 years, healthcare utilization status for the first 3 months after registration was expanded to healthcare utilization statistics for the first 12 months after registration, thereby improving the accuracy of disease burden measurement. Furthermore, the geographic unit of analysis was disaggregated from the previous seven metropolitan regions to the 17 province-level administrative districts. In the 2022 Annual Report, published in 2024, the approaches for statistics analyses were enhanced. To diversify the analysis of mortality, an item for the number of deaths by disease and sex was newly added. Additionally, the decedent age group and incident case age group, which were previously managed differently, were standardized to 10-year intervals, ensuring linkage between result tables. Moreover, the status of healthcare utilization by type of health security (national health insurance or medical aid) was introduced as a new item, establishing a foundation for understanding healthcare utilization among the vulnerable population. In the 2023 Annual Report, published in 2025, the comprehensiveness of the data was expanded. Previously, the status by age and region was disclosed only for diseases with more than 200 incident cases; however, this list was expanded to apply to all rare diseases. However, to minimize the risk of personal identification, a balance was struck between the openness and information security of national health and medical data through limited disclosure, whereby detailed items are not revealed in cases where the count is three or fewer.

As such, longitudinally examining the dynamic changes and data of the Annual Report accumulated over the past 5 years goes beyond a simple confirmation of statistical figures and becomes core foundational data for tracking the development process of the national rare disease healthcare data system and identifying rare disease occurrence trends. Previous studies have also achieved the accomplishment of presenting the compilation method for the Annual Report and the demographic distribution and scale of medical expenses of newly incident cases for the corresponding year [17-19]. However, the list of rare diseases is continuously expanding every year, and accordingly, the influx of new patients, the patterns of high-frequency diseases, and medical expenses are also newly changing every year. Therefore, it is necessary to analyze and share the most recently published statistical results to secure the timeliness of healthcare policy and to establish the direction of rare disease management. To this end, this study, by utilizing the Annual Report from 2019–2023, intends to longitudinally analyze the national rare disease occurrence patterns and, at the same time, to analyze, in detail, the rare disease occurrence status for the year 2023.

Methods

1. Study Design

This study is a descriptive statistics-based retrospective analysis conducted to identify the status and characteristics of the incidence, mortality, and healthcare utilization of rare diseases in the Republic of Korea (ROK) using data from the Annual Report published over the past 5 years.

2. Study Population and Data Collection Methods for the 「Annual Report on the Rare Disease Patients in Korea」

1) Definition and criteria of the study population

The newly incident patients with rare diseases in the ROK covered by the Annual Report are individuals who were first registered as beneficiaries of the Special Copayment Reduction Program for Rare Diseases for diseases classified as nationally managed rare diseases announced by the Korea Disease Control and Prevention Agency (KDCA). Among these patients, new registrants for a given year are finalized by restricting the cohort to individuals whose “Effective Start Date of the Special Copayment Reduction Program for Rare Diseases” falls between January 1 and December 31 of that year, based on the Special Copayment Reduction Program for Rare Diseases data finally collected by December 31 of the following year, taking into consideration potential administrative delays in registration.

2) Data collection methods

The Annual Report collects data individually from five related institutions (National Health Insurance Service, Korea Social Security Information Service, Health Insurance Review and Assessment Service, Ministry of the Interior and Safety, and Ministry of Data and Statistics), and the collected data are used after undergoing processes such as data cleaning and transformation according to the characteristics of each dataset. Information on beneficiaries of the Special Copayment Reduction Program for Rare Diseases is collected from the National Health Insurance Service and the Korea Social Security Information Service. Healthcare utilization information for the 12 months following the Effective Start Date of the Special Copayment Reduction Program for Rare Diseases for newly incident patients is collected from the Health Insurance Review and Assessment Service. Mortality information for newly incident patients during the corresponding year is collected from the Ministry of Data and Statistics. Address and residency status information for newly incident patients are collected from the Ministry of the Interior and Safety.

3) Analytical methods for the 「Annual Report on the Rare Disease Patients in Korea」

The raw data on beneficiaries of the Special Copayment Reduction Program for Rare Diseases, collected from the National Health Insurance Service and the Korea Social Security Information Service, contain multiple duplicate cases for the same patient, as update histories resulting from modifications to patient demographic information, disease changes, eligibility changes, and other revisions are cumulatively recorded in the form of log data. Therefore, a connected-component analysis was conducted to identify duplicate patients by recognizing eligibility information for the same individual entered at different time points as a single entity when the records could be linked together through identifier variables. During the construction of the final analysis dataset, a single value was finalized for each patient by selecting only the most recent data record without logical errors from among the multiple log records sorted by patient. Among these, only patients with no registration history for the Special Copayment Reduction Program for Rare Diseases in previous years were filtered to identify the final cohort of newly incident patients with rare diseases. The disease information (disease classification code and disease classification code serial number) recorded in the Special Copayment Reduction Program for Rare Diseases data for the finally selected newly incident patients was converted into disease codes and Korean and English disease names in accordance with the annually announced list of rare diseases eligible for the Special Copayment Reduction Program for Rare Diseases. Additionally, for these finally selected newly incident patients, the result tables for the Annual Report were generated by linking healthcare utilization data (Health Insurance Review and Assessment Service) for the 12 months following registration for the Special Copayment Reduction Program for Rare Diseases, mortality data for the corresponding year (Ministry of Data and Statistics), and address data (Ministry of the Interior and Safety).

3. Data Analysis Methods

In this study, the following analyses were conducted to identify the incidence patterns of rare diseases in the ROK and the detailed occurrence status in 2023. First, annual trends in the number of nationally managed rare diseases announced by the KDCA, the number of incident cases, and the number of deaths in the corresponding year were comparatively analyzed for 2019–2023. At this stage, the occurrence status of incident cases was analyzed by sex (male and female) and disease group (rare diseases, extremely rare diseases, and other chromosomal abnormality disorders), while mortality status was analyzed by disease group. To examine medical expenditure patterns during the 12 months following registration for the Special Copayment Reduction Program for Rare Diseases, healthcare utilization status for the 3-year period from 2021 to 2023, when these statistics began to be reported consecutively, was analyzed. Second, using the 2023 Annual Report, the occurrence status of rare diseases by age and region, as well as the status of frequently occurring rare diseases, was examined from multiple perspectives. Occurrence status by age was presented in 10-year age groups, and occurrence status by region was presented for the 17 provincial-level administrative districts. For frequently occurring rare diseases, the top five high-frequency diseases were identified by sex and age group to determine the incidence distribution according to demographic characteristics. To analyze the financial burden of disease, the top five diseases were identified based on total annual medical expenses and average medical expenditure per capita.

Results

1. Annual Trends in the Status of Incidence, Mortality, and Healthcare Utilization of Rare Diseases

An analysis of 5-year data from 2019 to 2023 (Table 1) showed that the designated rare disease list expanded from 926 in 2019 to 1,165 in 2023. Accordingly, the number of rare diseases with registered incident patients in the ROK also increased from 636 in 2019 to 784 in 2023. The number of incident cases remained at approximately the mid-50,000 level annually from 2019 (55,549) through 2022 (54,952), but reached 62,420 in 2023. Regarding the trend in occurrence by sex, there were more female incident cases in 2019, 2020, and 2022 and more male incident cases in 2021 and 2023; however, the overall distribution of incident cases by sex remained similar, with no marked disparity between males and females.

Table 1. Annual trends in rare disease incidence and deaths.

Category			2019	2020	2021	2022	2023
No. of rare diseases			926	1,014	1,086	1,123	1,165
No. of occurring rare diseases			636	694	753	770	784
No. of incident cases	Total		55,549	52,310	55,874	54,952	62,420
	Sex	Male	26,171	25,353	27,976	27,357	31,614
		Female	29,378	26,957	27,898	27,595	30,806
	Group	Rare diseases	54,728	50,455	53,967	52,790	59,797
		Ultra-rare diseases	775	1,767	1,820	2,074	2,510
		Other chromosomal abnormalities	46	88	87	88	113
No. of deaths	Total		1,596	1,662	1,845	1,902	2,093
	Group	Rare diseases	1,595	1,643	1,826	1,871	2,044
		Ultra-rare diseases	1	18	19	31	49
		Other chromosomal abnormalities	0	1	0	0	0
Healthcare utilizationa)	Patients		-	-	49,772	52,818	60,050
	Total medical expenses (billion KRW)		-	-	307.2	337.4	391.5
	Medical expenses per capita (KRW 10,000)	Total	-	-	617	639	652
		Insurance benefit	-	-	553	572	584
		Co-payment	-	-	64	66	68

-=not available. ^a)Healthcare utilization data within 12 months of registration have been provided since the 2021 annual report.

In the distribution of incident cases by disease group, rare diseases accounted for more than 95% of all incident cases each year. Extremely rare diseases and other chromosomal abnormality disorders increased substantially over the past 5 years. The number of incident cases of extremely rare diseases increased by more than 3.2-fold, from 775 in 2019 to 2,510 in 2023, while the number of incident cases of other chromosomal abnormality disorders also increased by approximately 2.5-fold, from 46 in 2019 to 113 in 2023.

Meanwhile, the number of deaths occurring in the corresponding year among incident cases in the corresponding year also showed an increasing trend. The number of deaths increased annually from 1,596 in 2019 to 2,093 in 2023. In the distribution of deaths by disease group, most deaths were concentrated in the rare disease group, while the number of deaths in the extremely rare disease group increased from one in 2019 to 49 in 2023.

The annual number of unique patients receiving medical care during the 12 months following registration for the Special Copayment Reduction Program for Rare Diseases increased from 49,772 in 2021 and 52,818 in 2022 to 60,050 in 2023. The annual total medical expenses for patients with rare diseases increased from KRW 307.2 billion in 2021 to KRW 337.4 billion in 2022 and KRW 391.5 billion in 2023, while the average total medical expenses per patient increased from KRW 6.17 million in 2021 to KRW 6.39 million in 2022 and reached KRW 6.52 million in 2023.

2. Occurrence Status of Rare Diseases by Age Group and Region as of 2023

Regarding the distribution of cases by age group in 2023, the 60–69-year age group accounted for the highest proportion, with 12,078 cases (19.3%), followed by the 50–59-year age group with 10,123 cases (16.2%) and the 70–79-year age group with 8,509 cases (13.6%) (Figure 1). The number of incident cases by region was the highest in Gyeonggi-do, with 16,631 cases (26.6%), followed by Seoul Metropolitan City, with 12,375 cases (19.8%) (Figure 2).

Figure 1. Number of new rare disease patients by age group in 2023.

Figure 2. Number of new rare disease patients by province in 2023.

^a)When the registered residential address was unidentifiable or the address on the application was invalid.

3. Occurrence Status of the Top Five Rare Diseases as of 2023

The status of the top five rare diseases in 2023 based on the number of incident cases and total medical expenses is shown in Table 2. In 2023, idiopathic pulmonary fibrosis had the highest number of incident cases (5,543), followed by polycystic kidney, autosomal dominant (autosomal dominant polycystic kidney disease, ADPKD) (4,830) and irreversible dilated cardiomyopathy (3,367). Among males, idiopathic pulmonary fibrosis ranked first (4,308), followed by ADPKD (2,562) and irreversible dilated cardiomyopathy (2,266). Among females, systemic lupus erythematosus with organ or system involvement was the most common (2,346), followed by ADPKD (2,268) and sicca syndrome (Sjögren, 2,093), demonstrating differences in the distribution of the top diseases by sex.

Table 2. Incidence status of the top 5 rare diseases in 2023.

Category		Rank 1	Rank 2	Rank 3	Rank 4	Rank 5
Total (case)		Idiopathic pulmonary fibrosis (5,543)	Polycystic kidney, autosomal dominant (4,830)	Irreversible dilated cardiomyopathy (3,367)	Systemic lupus erythematosus with organ or system involvement (2,718)	Moyamoya disease (2,372)
Sex (case)	Male	Idiopathic pulmonary fibrosis (4,308)	Polycystic kidney, autosomal dominant (2,562)	Irreversible dilated cardiomyopathy (2,266)	Crohn’s disease of both small and large intestine (1,686)	Nonobstructive hypertrophic cardiomyopathy (831)
	Female	Systemic lupus erythematosus with organ or system involvement (2,346)	Polycystic kidney, autosomal dominant (2,268)	Sicca syndrome (Sjögren) (2,093)	Moyamoya disease (1,559)	Idiopathic pulmonary fibrosis (1,235)
Age (case)	<1 yr	Tetralogy of Fallot (96)	Coarctation of aorta (75)	Spina bifida, unspecified (69)	Craniosynostosis (62)	West’s syndrome (60)
	1−9 yrs	Neurofibromatosis (nonmalignant) type 1, type 2 (106)	Moyamoya disease (84)	Juvenile rheumatoid arthritis (74)	Status epilepticus, unspecified (73)	Microtia (70)
	10−19 yrs	Crohn’s disease of both small and large intestine (656)	Narcolepsy and cataplexy (269)	Juvenile rheumatoid arthritis (223)	Crohn’s disease of small intestine (176)	Crohn’s disease of large intestine (143)
	20−29 yrs	Crohn’s disease of both small and large intestine (739)	Narcolepsy and cataplexy (475)	Systemic lupus erythematosus with organ or system involvement (404)	Crohn’s disease of small intestine (295)	Crohn’s disease of large intestine (219)
	30−39 yrs	Polycystic kidney, autosomal dominant (605)	Systemic lupus erythematosus with organ or system involvement (479)	Crohn’s disease of both small and large intestine (376)	Moyamoya disease (344)	Keratoconus (283)
	40−49 yrs	Polycystic kidney, autosomal dominant (1,273)	Systemic lupus erythematosus with organ or system involvement (595)	Moyamoya disease (499)	Irreversible dilated cardiomyopathy (449)	Sicca syndrome (Sjögren) (405)
	50−59 yrs	Polycystic kidney, autosomal dominant (1,376)	Irreversible dilated cardiomyopathy (639)	Sicca syndrome (Sjögren) (615)	Moyamoya disease (577)	Systemic lupus erythematosus with organ or system involvement (481)
	60−69 yrs	Idiopathic pulmonary fibrosis (1,499)	Polycystic kidney, autosomal dominant (921)	Irreversible dilated cardiomyopathy (807)	Sicca syndrome (Sjögren) (630)	Moyamoya disease (432)
	70−79 yrs	Idiopathic pulmonary fibrosis (2,251)	Irreversible dilated cardiomyopathy (673)	Polymyalgia rheumatica (319)	Polycystic kidney, autosomal dominant (309)	Nonobstructive hypertrophic cardiomyopathy (275)
	≥80 yrs	Idiopathic pulmonary fibrosis (1,464)	Irreversible dilated cardiomyopathy (455)	Bullous pemphigoid (437)	Status epilepticus, unspecified (310)	Polymyalgia rheumatica (158)
Annual medical expenses (KRW 1,000)	Total	Idiopathic pulmonary fibrosis (40,453,095)	Status epilepticus, unspecified (36,732,908)	Polycystic kidney, autosomal dominant (26,302,326)	Guillain–Barré syndrome (23,575,310)	Moyamoya disease (19,704,339)
	Per capita average	Gaucher’s disease (318,423)	Morquio(-like)(classic) syndrome (245,701)	Mucopolysaccharidosis, type II (213,268)	Pompe’s disease (166,219)	Hurler-Scheie syndrome (162,846)

According to the age-group analysis, the most frequently occurring diseases were Tetralogy of Fallot among those aged under 1 year, neurofibromatosis (non-malignant) types 1 and 2 among those aged 1–9 years, Crohn’s disease involving both small intestine and colon among those in their teens and twenties, ADPKD among those in their thirties to fifties, and idiopathic pulmonary fibrosis among those aged 60 years or older.

The disease with the highest annual total medical expenses was idiopathic pulmonary fibrosis, totaling KRW 40.45 billion, followed by status epilepticus, unspecified (KRW 36.73 billion) and ADPKD (KRW 26.30 billion). The highest average medical expenditure per capita was observed for Gaucher disease KRW 318.42 million, followed by Morquio(-like)(classic) syndrome (KRW 245.70 million) and mucopolysaccharidosis type II (KRW 213.27 million).

Discussion

This study was conducted to provide empirical evidence on the occurrence status of rare diseases in the ROK by longitudinally reviewing the Annual Report from 2019 to 2023 and analyzing the characteristics of incident cases reported in the latest 2023 data. Changes in the compilation framework of the Annual Report over the past 5 years demonstrate that the report has matured into foundational data supporting health policy and clinical practice in the ROK. In particular, the structural issue whereby statistics from different years were mixed within the same annual report was addressed by extending the data follow-up period, and the timeliness and precision of the data were improved by integrating incidence, mortality, and healthcare utilization into a single annual report. Furthermore, extending the follow-up period for healthcare utilization to 12 months established a foundation for empirically assessing patients’ annual burden of healthcare costs. Subdividing the geographic unit of analysis into the 17 metropolitan cities and provinces and newly introducing benefit status by type of medical security represented a turning point in improving public health equity by enabling the monitoring of disparities according to place of residence and income level [6]. The decision to disclose age- and region-specific occurrence status even for rare diseases with 200 or fewer incident cases was also consistent with the United Nations General Assembly resolution and the global research governance framework, which call for the collection and dissemination of disaggregated data by sex, age, income, and race at the national level to strengthen international cooperation [15,16]. In this process, to protect personal information and prevent personal identification, a balance between data utility and security was achieved by disclosing only categories with more than three incident cases.

An examination of the annual number of incident cases of rare diseases showed that the rare disease list, the number of diseases with incident cases, and the annual number of incident cases all exhibited a continuous increasing trend. This finding suggests that the scope of rare disease designation has gradually expanded and that new diagnoses are being made across a broader range of diseases as a result of advances in diagnostic technology and improved disease awareness [1,20,21]. In particular, the number of incident cases reached 62,420 in 2023, exceeding 60,000 for the first time since the publication of the Annual Report. This increase was confirmed to reflect the impact of rare diseases newly designated and officially announced in 2023. Compared with 2022, a total of 42 diseases were newly added to the rare disease list in 2023 (1 rare disease, 20 extremely rare diseases, and 21 other chromosomal abnormality disorders), and no diseases were removed. Within these newly designated diseases, a total of 5,250 incident cases were identified. In particular, ADPKD, one of the newly designated diseases, accounted for 4,830 incident cases and was identified as the primary contributor to the increase in incident cases [13]. However, this increase is subject to administrative limitations in the statistical derivation: because ADPKD was newly designated as a rare disease in 2023, patients who had developed the condition prior to that year were officially registered and thus counted as ‘incident cases’ only upon their registration in 2023. Consequently, these figures encompass both true epidemiological occurrence and individuals whose disease onset occurred before 2023 but who were incorporated into the current year’s counts due to administrative timing, necessitating cautious interpretation when evaluating the 2023 incidence scale. Furthermore, over the past 5 years, the number of incident cases of extremely rare diseases increased by approximately 3.2-fold, while the number of incident cases of other chromosomal abnormality disorders increased by approximately 2.5-fold. The increase in incident cases among these smaller disease groups may be interpreted as reflecting the policy achievement of progressively expanding the designation of nationally managed rare diseases and incorporating potential patient populations that had previously remained in the blind spot of public health and medical care into the healthcare system [16]. However, the increase in the number of deaths in the extremely rare disease group, together with the increase in incident cases, suggests that clinical vulnerabilities inherent to these smaller disease groups, including prolonged time to definitive diagnosis and the lack of standard treatments, still exist [2,3,22]. Nevertheless, the annual number of deaths has the interpretational limitation that deaths directly due to a rare disease cannot be clearly distinguished from deaths due to other diseases or external causes.

From the perspective of healthcare utilization, total medical expenses also continued to increase. In particular, the five diseases with the highest total medical expenses, including idiopathic pulmonary fibrosis and status epilepticus, unspecified, accounted for 35.9% of the total medical expenses for all rare diseases. These findings suggest that, in addition to expanding inclusiveness, future rare disease support policies will also require efficient financial management and monitoring strategies for disease groups with the greatest financial burden. Meanwhile, the five diseases with the highest average total annual medical expenses per patient included Gaucher disease and Morquio(-like)(classic) syndrome, indicating a pattern different from that of diseases with the highest total medical expenses. Therefore, a multifaceted system for strengthening coverage is required to comprehensively cover patients with rare diseases who have relatively small patient populations but a high per-capita medical expense burden without leaving any blind spots. However, because diseases with the highest average total annual medical expenses per patient have extremely small annual numbers of incident cases, the possibility that individual observations acted as outliers cannot be excluded. Therefore, long-term follow-up analyses should be conducted to derive average medical expenses that are clinically relevant and policy-relevant. Furthermore, to take into account the impact of the expansion of nationally managed rare diseases, newly designated and previously designated diseases should be analyzed separately, and disease-specific mortality and medical expenses should be analyzed as a time series to identify the cumulative effects of disease expansion and changes in actual healthcare utilization.

Finally, analyses of the occurrence status of rare diseases by age group and region and of frequently occurring rare diseases showed that rare diseases differed according to sex, region, and age. This finding indicates that rare diseases constitute a multi-layered, heterogeneous group that cannot simply be classified as a single disease category and suggests that the clinical problems and socioeconomic needs faced by patients may vary according to demographic characteristics [6]. According to the existing literature, during infancy, childhood, and adolescence, lifelong treatment and the caregiving burden on the entire family become the primary concerns, whereas women of childbearing age experience difficulties related to pregnancy and childbirth because of their disease. In contrast, older patients with rare diseases may experience compounded difficulties as the pathophysiology of rare diseases combines with declining physical function, making independent daily living more difficult [23-25]. Therefore, rare disease health policies should establish a customized support system for each life cycle stage by stratifying the target population of patients with rare diseases according to the distinct disease characteristics of different demographic groups.

In conclusion, this study is significant in that it empirically identified the patterns of change in rare disease statistics over the past 5 years and the latest occurrence status for 2023. The Annual Report can serve not only as evidence-based data on the occurrence status of rare diseases in the ROK but also as a robust evidence base for proactively forecasting healthcare resource needs associated with the expansion of the rare disease list and for monitoring policies aimed at reducing community health disparities. However, future improvements to the statistical system should extend beyond compiling the number of incident cases to include incidence rates, survival rates, and the overall prevalence of rare diseases, thereby enabling more precise tracking and assessment of demographic and life cycle vulnerabilities.