| AIDS | Retrovir | Orphan Designation | - |
| AIDS dementia complex | Mepron | Orphan Designation | - |
| AIDS-related disorder | Mepron | Orphan Designation | - |
| Bailey-Bloch congenital myopathy | Epoprostenol | Orphan Designation | - |
| COVID-19–associated multisystem inflammatory syndrome in children | Digibind | Orphan Designation | - |
| Ehlers-Danlos syndrome, classic type, 1 | Exosurf Neonatal for Intratracheal Suspension | Orphan Designation | - |
| Ehlers-Danlos syndrome, dermatosparaxis type | Exosurf Neonatal for Intratracheal Suspension | Orphan Designation | - |
| Emanuel syndrome | Flolan | Orphan Designation | - |
| HIV-associated nephropathy | Mepron | Orphan Designation | - |
| Kaposi's sarcoma | Mepron | Orphan Designation | - |
| Larsen-like syndrome, B3GAT3 type | Alkeran For Injection | Orphan Designation | - |
| PEHO syndrome | Digibind | Orphan Designation | - |
| Pearson syndrome | Carbovir | Orphan Designation | - |
| advanced heart failure | Retrovir | Orphan Designation | - |
| advanced sleep phase syndrome | Retrovir | Orphan Designation | - |
| advanced sleep phase syndrome 1 | Retrovir | Orphan Designation | - |
| advanced sleep phase syndrome 3 | Retrovir | Orphan Designation | - |
| alopecia-intellectual disability syndrome 2 | Mepron | Orphan Designation | - |
| anogenital human papillomavirus infection | Interferon alfa-nl | Orphan Designation | - |
| autosomal recessive congenital ichthyosis 11 | Monolaurin | Orphan Designation | - |
| bilirubin induced brain injury in the newborn | Exosurf Neonatal for Intratracheal Suspension | Orphan Designation | - |
| bronchiectasis with or without elevated sweat chloride 2 | Digibind | Orphan Designation | - |
| central nervous system AIDS arteritis | Mepron | Orphan Designation | - |
| chronic primary adrenal insufficiency | Flolan | Orphan Designation | - |
| classic stiff person syndrome | CarbovirFlolan | Orphan Designation | - |
| colorectal cancer | Retrovir | Orphan Designation | - |
| congenital contractural arachnodactyly | Alkeran For Injection | Orphan Designation | - |
| congenital heart defects, multiple types, 8, with or without heterotaxy | Alkeran For Injection | Orphan Designation | - |
| congenital primary megaureter | Monolaurin | Orphan Designation | - |
| congenital primary megaureter, obstructed form | Monolaurin | Orphan Designation | - |
| developmental and epileptic encephalopathy, 40 | Exosurf Neonatal for Intratracheal Suspension | Orphan Designation | - |
| human papillomavirus-related penile squamous cell carcinoma | Interferon alfa-nl | Orphan Designation | - |
| human papillomavirus-related squamous cell carcinoma | Interferon alfa-nl | Orphan Designation | - |
| idiopathic pulmonary arterial hypertension | Flolan | Orphan Designation | - |
| metastatic malignant neoplasm in the colon | Exosurf Neonatal for Intratracheal Suspension | Orphan Designation | - |
| metastatic malignant neoplasm in the lymph nodes | Exosurf Neonatal for Intratracheal Suspension | Orphan Designation | - |
| metastatic malignant neoplasm in the spinal cord | Exosurf Neonatal for Intratracheal Suspension | Orphan Designation | - |
| myopathy, distal, 7, adult-onset, X-linked | Epoprostenol | Orphan Designation | - |
| myopathy, myofibrillar, 13, with rimmed vacuoles | Epoprostenol | Orphan Designation | - |
| neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities | Alkeran For Injection | Orphan Designation | - |
| newborn respiratory distress syndrome | Exosurf Neonatal for Intratracheal Suspension | Orphan Designation | - |
| pulmonary hypertension, primary, 1 | Flolan | Orphan Designation | - |
| pulmonary hypertension, primary, 2 | Flolan | Orphan Designation | - |
| pulmonary hypertension, primary, 3 | Flolan | Orphan Designation | - |
| pulmonary hypertension, primary, 4 | Flolan | Orphan Designation | - |
| pulmonary hypertension, primary, 6 | Flolan | Orphan Designation | - |
| respiratory distress syndrome in premature infants | Exosurf Neonatal for Intratracheal Suspension | Orphan Designation | - |
| stiff-person syndrome | Carbovir | Orphan Designation | - |
| thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies | Alkeran For Injection | Orphan Designation | - |