The catalog is dominated by Disease (41%), followed by Category (19%) and Malformation Syndrome (18%). Clinical subtypes, morphological anomalies, and clinical groups account for the remaining quarter.
65% are individual disorders, 23% are groups of disorders (umbrella categories), and 12% are subtypes of existing disorders.
Neonatal (3,091) and Infancy (2,566) dominate — over 50% of rare diseases manifest in the first year of life. Adult-onset accounts for 1,486 entries. Elderly onset is the rarest documented category (347).
Breaking onset into lifecycle phases shows the overwhelming pediatric burden. The pre-birth + newborn window (Antenatal + Neonatal) alone covers 4,024 entries. Only a minority are primarily adult conditions.
Autosomal recessive is the single most common mode (2,599 entries), narrowly ahead of autosomal dominant (1,943). X-linked recessive accounts for 388 entries — predominantly affecting males. Mitochondrial inheritance is rare (39).
Counting all recessive modes (autosomal + X-linked + mitochondrial) vs. dominant modes, recessive conditions outnumber dominant ones by ~1.6:1. This ratio is clinically significant for genetic counseling and carrier screening.
Congenital Anomalies (Q-codes) dominate with 2,916 entries — nearly 4x the next category. Nervous System disorders and Endocrine/Metabolic diseases each account for ~1,026 entries, highlighting the outsized role of neurological and metabolic rare diseases.
The top 5 ICD-10 chapters together cover ~65% of all coded rare diseases.
ICD-10 covers 65.8% of records vs only 53.6% for ICD-11 — revealing a significant transition gap as the field moves to the newer standard.
UMLS has the highest coverage at 84.1%, making it the most universally linked identifier. GARD has the lowest at 33.5%, indicating many rare diseases lack US registry representation. MedDRA coverage is just 7.4%.
The two most clinically critical fields — Age of Onset (41.2% missing) and Inheritance Pattern (47.9% missing) — have the largest gaps, limiting genomic counseling utility for nearly half the database.
| Field | Present | Missing | Coverage |
|---|
Malformation syndromes are overwhelmingly Neonatal/Antenatal (prenatal detectability). Diseases show a more even spread — including significant Adult onset. Categories are broadly distributed across all ages.
For pure Diseases, autosomal recessive leads (31%). For Malformation Syndromes, recessive and dominant are nearly equal (~28% each), reflecting heterogeneous developmental pathway disruptions.
Early-onset diseases (Neonatal/Infancy/Antenatal) show a strong autosomal recessive skew — metabolic enzyme deficiencies and structural protein defects manifest at birth. Late-onset diseases (Adult/Elderly) show a higher proportion of autosomal dominant and multifactorial conditions.
The word "Syndrome" appears in 3,284 disease names — 29% of all entries — making it the dominant nomenclature pattern. "Disease" appears in 882 names. Deficiency (702) and Dysplasia (395) reveal common mechanistic themes.
Of the 5,965 records with known inheritance, 872 (14.6%) have two or more inheritance modes listed, suggesting conditions with variable expressivity, heterogeneous mutations, or incomplete documentation. The most common combo: AD + AR (251 cases).
The most common onset combination is Infancy + Neonatal (1,466 cases), indicating diseases that appear at birth or within months. "All ages" (867) is the second most common — suggesting chronic conditions present throughout life.
OrphaCodes are assigned sequentially, making code ranges a proxy for discovery era. Codes ≥50,000 account for 75.8% of all records — reflecting explosive growth in rare disease characterization in recent decades driven by genomics.
Codes <1000 (oldest): 872 · Codes 1K–50K: 1,901 · Codes ≥50K (newest): 8,683
Among the 493 X-linked disorders (XLR + XLD), X-linked recessive dominates at 79% — conditions affecting predominantly males. X-linked dominant (105) often have female-skewed or lethal-in-males profiles. X-linked diseases peak in Neonatal/Infancy onset.
Among the 7,541 ICD-10 coded entries, Congenital Anomalies represent 38.7% — nearly 4× the next largest system. Neurological + Metabolic together comprise another 27%, reinforcing that rare diseases disproportionately affect the brain and metabolism.
Assessing 6 critical fields across all 11,456 records reveals that the database has strong identifier coverage (UMLS, ICD-10) but critical gaps in clinical metadata (onset, inheritance) — the fields most important for patient care and research.