A systems perspective on rare diseases: integrating human phenotype ontology with the Anukta framework of Ayurveda

Abstract

Rare diseases, though individually uncommon, collectively affect millions and remain among the most underdiagnosed and poorly managed conditions in conventional healthcare. Ayurveda, with its systems approach and emphasis on Dosha imbalance, offers a complementary lens to interpret such unlisted conditions, known as Anukta Vyadhi. Human Phenotype Ontology (HPO) that catalogs 10,610 phenotypes across 12,678 rare diseases can be used to bridge modern phenotype vocabularies and Ayurvedic classifications. This study explores whether integrating the Anukta framework can enable meaningful assessment of rare diseases in Ayurveda clinical settings. A curated list of 140 Nanatmaja Vikara (NV)-Vata (80), Pitta (40), and Kapha (20) was mapped to HPO terms, preserving the semantic context of Ayurvedic descriptions. Noteworthy, 128 of NV phenotypes mapped to 199 HPO terms. Over 7200 rare diseases had representation of Nanatmaja Vikara. Vata-linked features were the most enriched (4786), followed by Pitta (465) and Kapha (240). 1349 of diseases showed dual Dosha involvement and 360 of all three. Seizures, short stature, and ptosis were most prevalent features of nV; gastroesophageal reflux, fever, and abnormal skin blistering of nP; and obesity, lethargy, and pallor of nK. Detailed case interpretation of Steinert Myotonic Dystrophy, Syndromic Diarrhea and Alstrom Syndrome revealed association with Vata-Kapha, Vata-Pitta, and Tridosha features respectively. This integration of Anukta framework with structured ontologies provides a practical pathway for understanding rare diseases for management in Ayurveda clinics and integrative decision-making when biomedical options are limited.