Rare Diseases in Southeast Asia: Definition of Rare disease

Southeast Asia Rare Disease self-study, Part 1

May 2025, Swift Evo, https://x.com/swiftevo1

Introduction

Disclaimer: This report is intended purely for self-study and is not a rigorous scientific publication. It has not undergone peer review and should not be used for academic analysis. Readers should do their own research, and the analysis is done under the support of AI.

Rare diseases, often debilitating or life-threatening, affect a small percentage of the population but collectively impact around 10% of individuals worldwide.

Rare diseases, orphan drugs, and their regulation in Asia: Current status and future perspectives. Intractable Rare Dis Res. 2012;1(1):3–9.

Regional definitions vary, reflecting population sizes, healthcare systems, and policy priorities. This report, the first in the Southeast Asia Rare Disease self-study, compares rare disease definitions in Japan, Korea, India, China, Malaysia, Taiwan and Hong Kong, alongside the United States and European Union for global context.

Regional Definitions of Rare Diseases

Global (WHO)

Ref: https://conect4children.org/2024/03/01/rarediseaseday/

In December 2019, the WHO and RDI established an operational definition of rare diseases as medical conditions with a specific pattern of clinical signs, symptoms, and findings affecting fewer than or equal to 1 in 2,000 persons (0.5‰ or 0.5 per 1,000) [14,15]. This includes rare genetic diseases, cancers, infectious diseases, poisonings, immune-related diseases, and more, focusing on clinical and qualitative challenges.

The cumulative prevalence of 6,000–8,000 rare diseases is estimated at 3–8%. 242.7–647.2 million people are affected by different rare diseases globally, reflecting the broader impact [16].

United States

Ref:https://www.facebook.com/nhhospitals/photos/did-you-know-that-there-are-25-30-million-americans-who-are-impacted-by-rare-dis/786452400177022/?_rdr

The United States’ Rare Diseases Act (2002) defines rare diseases as those affecting fewer than 200,000 individuals, or approximately 0.75‰ (0.75 per 1,000) with a 341 million population [1].

There are 25 – 30 million patients affected by different rare disease in United States. Nearly 7,000 rare diseases have been identified. [1, 18]

European Union

Ref: https://www.eurordis.org/rare-disease-policy/30-million-reasons/

The European Union defines rare diseases as those affecting fewer than 5 per 10,000 persons, or 0.5‰ (0.5 per 1,000), per Regulation (EC) No 141/2000 (1999) [1]. With a 549 million population, approximately 274,500 individuals are affected in one rare disease [1]. There are 27 – 36 million patients affected by 6,000-8,000 different rare disease in Europe. [1, 19]

Japan

Ref: https://www.nature.com/articles/ejhg2017106/figures/1

Japan’s Revised orphan drug regulations (amendment of the Pharmaceutical Affairs Act and Drug Fund for Adverse Reaction Relief and Research Promotion Act) (1993) defines rare diseases, originally termed “intractable diseases” (Nan-byo), as those targeted disease affecting fewer than 50,000 patients, or approximately 0.4‰ (0.4 per 1,000) with a 125 million population [4,5].

In Japan, the total population with a severe condition because of rare and intractable diseases is fewer than 120,000 (0.96‰) [5]. 333 rare diseases have been designated as Nan-byo in 2021. [19]

Korea

Ref: https://www.kord.or.kr/

Korea’s Rare Disease Management Act (2016) defines rare diseases as those affecting fewer than 20,000 individuals, or approximately 0.4‰ (0.4 per 1,000) with a 52.05 million population, or diseases lacking treatment [2].

According to Korean Organization for Rare Diseases (http://www.kord.or.kr), there are 2,000 different rare diseases identified in Korea, around 0.8 million patients affected by rare diseases and untreatable diseases [16].

China

Ref: https://web.shobserver.com/sgh/detail?id=1265264

China has no legislative definition, but a 2010 Expert Seminar proposed a prevalence of fewer than 1 in 500,000 (0.002‰ or 0.002 per 1,000) or neonatal morbidity of fewer than 1 in 10,000 (0.1‰) [10].

With a 1.408 billion population, if those disease affecting fewer than 140,800 patients was defined as rare disease. The Compendium of China’s First List of Rare Diseases (2018) clarified the concept but lacks a precise threshold. 121 rare diseases were in this list [11]. In 2023, the National Health Commission of China officially announced the "Second List of Rare Diseases" of 86 rare diseases [21]. In total, there were 207 rare diseases were in these two lists.

China rare disease definition research report 2021 estimated there were 20 million rare disease patients in China. [24]

India

Ref:https://www.linkedin.com/pulse/rare-diseases-india%E0%A4%AD%E0%A4%B0%E0%A4%A4-%E0%A4%AE-%E0%A4%A6%E0%A4%B0%E0%A4%B2%E0%A4%AD-%E0%A4%AC%E0%A4%AE%E0%A4%B0%E0%A4%AF-anuj-kumar-5pzxc/

India lacks a standardized definition. The Indian Council of Medical Research (ICMR) defines rare diseases as affecting fewer than 1 in 2,500 (0.4‰ or 0.4 per 1,000), while the Organization for Rare Diseases India (ORDI) proposes 1 in 5,000 (0.2‰ or 0.2 per 1,000) [7].

With a 1.458 billion population, this estimates 5.83 million (ICMR) or 2.92 million (ORDI) patients. The National Policy for Rare Diseases (2021) adopts a flexible approach [8]. 63 rare diseases are included in under this policy on recommendation of Central Technical Committee for Rare Diseases [8].

Malaysia

Ref: https://mrds.org.my/

Malaysia has no official definition. The Malaysian Rare Disorders Society (MRDS) defines rare diseases as affecting fewer than 1 in 4,000 (0.25‰ or 0.25 per 1,000), while the Ministry of Health (MOH) adopts 0.65%–1% (6.5‰–10‰) [9].

With a 34.72 million population, this estimates 8,680 (MRDS) or 225,680–347,200 (MOH) patients. The MOH is reviewing a formal definition due to data gaps [9].

Hong Kong

Ref: https://www.codexgenetics.com/blog/en/Understand-Genetic-Testing-and-Neurodegenerative-Diseases/

Hong Kong has no rare disease law. The Orphanet Rare Disease Ontology (ORDO) defines rare diseases as occurring in less than 1 in 2,000 (0.5‰ or 0.5 per 1,000), used locally and cross-referenced with ORPHAcodes, overcoming ICD-10’s 500-code limitation [12]. A 2018 study developed 1,084 disease codes to estimate healthcare burden, reporting a prevalence of 1 in 67 (14.93‰), possibly due to broad inclusion [12,13].

With a 7.28 million population, ORDO suggests ~3,640 patients, while the study estimates ~108,657. The Hospital Authority uses <50 per 100,000 (0.5‰) for management [13].

New Born Screening for inborn errors of metabolism (NBSIEM) began as a pilot program in October 2015. The list of diseases being screened was 29 in Oct 2019. An inherited metabolic disorder (IMD) was eventually confirmed in 47 infants between 2015 to 2022 in 125,688 newborns, making the prevalence of IMD in Hong Kong 1 in 2674 [22].

Taiwan

Ref: https://www.tfrd2.org.tw/tfrd_eng/

Taiwan’s Rare Disease Control and Orphan Drug Act (2000) classifies a disease as rare if its prevalence is less than 1 in 10,000 (0.1‰ or 0.1 per 1,000), has a genetic origin, and is difficult to diagnose and treat [2]. A 2003–2014 study reported prevalence increasing from 10.57 to 33.21 per 100,000 (0.1057‰ to 0.3321‰) [3]. With a 2025 population of 23.11 million population, the legal threshold suggests less than 1 in ~2,311 patients for one disease defined as rare disease, though actual numbers are higher due to improved diagnostics [3].

According to Taiwan Foundation for rare disorders, there are 247 diseases [17] According to Statistical Report of Rare Disease Confirmed Cases in Taiwan from Health Promotion Administration, 22461 rare disease cases were reported until Arp 2025 [23].

Conclusion

Table 1: Rare Disease Definitions Across Regions

Region	Definition	Prevalence (‰)	Population (2025, million)	Estimated Patients (million)	Source
Global (WHO)	≤1 per 2,000, includes genetic, cancers, infectious, etc.; 3–8% cumulative	0.5 (specific); 30–80 (cumulative)	8.09 billion	242 –647	[14–16]
United States	<200,000 individuals	0.75	341	25 - 30	[1, 18]
European Union	<5 per 10,000	0.5	549	27 - 36	[1, 19]
Japan	<50,000 patients, unknown etiology, no treatment	0.4	125	0.12	[4,5 & 19]
Korea	<20,000 patients or no treatment	0.4	52.05	0.8	[2, 6 & 16]
India	ICMR: <1 per 2,500; ORDI: <1 per 5,000	0.4 (ICMR), 0.2 (ORDI)	1.458 billion	5.83 (ICMR); 2.92 (ORDI)	[7,8]
China	Proposed: <1 per 500,000 or neonatal <1 per 10,000	0.002–0.1	1.408 billion	20	[10,11 21 & 24]
Malaysia	MRDS: <1 per 4,000; MOH: 0.65%–1%	0.25 (MRDS), 6.5–10 (MOH)	34.72	8,680 ppl (MRDS); 0.23 –0.35 (MOH)	[9]
Taiwan	<1 per 10,000, genetic, difficult to diagnose/treat	0.1 (reported 0.3321 in 2014)	23.11	22461 cases reported	[2,3, 17, 20 & 23]
Hong Kong	No law; ORDO: <1 in 2,000; study: 1 in 67	0.5 (ORDO), 14.93 (study)	7.28	3,640 (ORDO); 0.11 (study)	[12,13 & 22]

Definitions vary widely, reflecting population sizes and data availability (Table 1).

Ref: https://www.mdpi.com/1660-4601/20/6/4732

Rare disease definitions in East and Southeast Asia range from Taiwan’s precise 0.1‰ (2,311 patients) to Malaysia’s broad 0.25‰–10‰ (8,680–347,200 patients). The WHO’s 2019 operational definition (0.5‰, ~4.045 million globally) aligns with the EU and Hong Kong’s ORDO, emphasizing clinical complexity. Hong Kong’s 14.93‰ estimate (108,657 patients) suggests data challenges. Standardized definitions are critical for patient registries, treatment access, and policy development.

Future reports in this series will explore policy implementation, funding, and patient outcomes.

Reference

Song P, Gao J, Inagaki Y, Kokudo N, Tang W. Rare diseases, orphan drugs, and their regulation in Asia: Current status and future perspectives. Intractable Rare Dis Res. 2012;1(1):3–9. PMC4204590.
Chiu et al. Disease prevalence and policy analysis in Asia. Orphanet J Rare Dis. 2018;13:147. PMC6114034.
Hsu JC, Wu H-C, Feng W-C, Chou C-H, Lai EC-C, Lu CY. Disease and economic burden for rare diseases in Taiwan. PLoS ONE. 2018;13(9):e0204206. PMC6150502.
Ninomiya and Okura. Nationwide comprehensive epidemiological study of rare diseases in Japan using a health insurance claims database. Orphanet J Rare Dis. 2022;17:140. PMC140.
Sakushima K, Takeda H, Aoi Y. Orphan drug designation and development in Japan: 25 years of experience and assessment. 2021;20(12):893–894. PMID:33723413.
Qiao et al. Rare disease management in Korea. Orphanet J Rare Dis. 2022;17:352. PMC352.
The GUaRDIAN Consortium, Sivasubbu S, Scaria V. Genomics of rare genetic diseases—experiences from India. Hum Genomics. 2019;13:52. PMC52.
India Ministry of Health. National Policy for Rare Diseases 2021. rarediseases.mohfw.gov.in/uploads/Content/1624967837_Final-NPRD-2021.pdf (access date: May 8, 2025)
Shafie AA, Supian A, Ahmad Hassali MA, Ngu L-H, Thong M-K, Ayob H. Rare disease in Malaysia: Challenges and solutions. PLoS ONE. 2020;15(4):e0230850. PMC7117672.
He J, Kang Q, Hu J, Song P, Jin C. China’s first national list of rare diseases. Intractable Rare Dis Res. 2018;7(2):145–147. PMC.
National Health Commission of China. Compendium of China’s First List of Rare Diseases (2018). http://www.nhc.gov.cn/yzygj/s7659/201806/1b11b26a8f3e4c3e9f1f3f1c1f9b1e1c.shtml (access date: May 8, 2025)
Chiu et al. Rare disease nosologies in Hong Kong. Orphanet J Rare Dis. 2018;13:147. PMC6114034.
Chung CCY, Ng NYT, Ng YNC, et al. Socio-economic costs of rare diseases in Hong Kong. Lancet Reg Health West Pac. 2023;34:100711. PMC10240356.
Rare Diseases International. Agreement with the WHO. 2019. https://www.rarediseasesinternational.org/working-with-the-who/ (access date: May 8, 2025)
Rare Diseases International. Operational Description of Rare Diseases. 2022. https://www.rarediseasesinternational.org/wp-content/uploads/2022/08/INFOGRAPHIC-OPERATIONAL-DESCRIPTION-OF-RARE-DISEASES.pdf (access date: May 8, 2025)
The Korea Association of Rare and Incurable Diseases. https://www.kord.or.kr/bbs/content.php?co_id=010601 (access date: May 8, 2025)
TAIWAN Foundatioin For Rare Disorders. https://www.tfrd2.org.tw/tfrd_eng/index.php/rd1 (access date: May 8, 2025)
National Organization for Rare Disorders N. Rare Disease Information. https://rarediseases.org/rare-diseases/ (access date: May 8, 2025).
Hayashi S, Umeda T. 35 years of Japanese policy on rare diseases. Lancet. 2008; 372(9642):889±90. https://doi.org/10.1016/S0140-6736(08)61393-8 (access date: May 8, 2025) PMID: 18790305.
Health Promotion Administration MoHaW, MOHW Published List of Rare Diseases coded with ICD-10 in Taiwan website: https://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=43&pid=1065 (access date: May 8, 2025).
Tang M, Yang Y, Ye Z, Song P, Jin C, Kang Q, He J. Release and impact of China's "Second List of Rare Diseases". Intractable Rare Dis Res. 2023 Nov;12(4):251-256. doi: 10.5582/irdr.2023.01086. PMID: 38024584; PMCID: PMC10680157.
Belaramani KM, Chan TCH, Hau EWL, Yeung MCW, Kwok AMK, Lo IFM, Law THF, Wu H, Wong SSN, Lam SW, Ha GHY, Lau TPY, Wong TK, Or VWC, Wong RMS, Ming WL, Chow JCK, Yau EKC, Fu A, Chong JSC, Yau HC, Poon GWK, Ng KL, Chan KT, Lam YY, Hui J, Mak CM, Fung CW. Expanded Newborn Screening for Inborn Errors of Metabolism in Hong Kong: Results and Outcome of a 7 Year Journey. Int J Neonatal Screen. 2024 Mar 11;10(1):23. doi: 10.3390/ijns10010023. PMID: 38535127; PMCID: PMC10970889.
Statistical Report of Rare Disease Confirmed Cases in Taiwan, MAR, 2025, https://www.hpa.gov.tw/EngPages/Detail.aspx?nodeid=4891&pid=19005, (access date: May 8, 2025)
China rare disease definition research report 2021, http://www.diagnoschina.com/research/detail/nid-83, (access date: May 9, 2025)