Systemic Genetic & Rare Disease Mechanisms
This volume covers systemic-body genetic and rare diseases — one standalone page per disease — giving each a graded molecular mechanism, a reproducible burden position, and its established treatment. It is the jamming branch of the Jamming Physics programme.
This is the jamming branch of the programme → VP Theory (foundation). The brain, nervous system, heart, and affect are owned by the sibling neuro and mind whitepapers and are cross-referenced, not duplicated.
Reading order. The framework (§1) defines the classification, the deterministic burden index, and the grade legend. Each placed disease then has its own page (§2 onward), ordered by residual burden; the not-placed diseases and the mechanism-class cross-references follow, each disease still on its own page. The burden order is a provisional [H] prioritisation device, not a registry-locked ranking — treatments are accession-dated [L] (33 of 35), onset is lifted to registry [L] (Orphanet, 28 of 35) and disability to registry [L] (GBD 2013 disability weights, 13 of 35; order_locked 6 of 35); severity lifts to registry [L] where a dominant sequela carries a cited HPO Severity-modifier annotation (R8), and progression lifts to registry [L] where cited PMC open-access literature gives a disease-level magnitude with a frozen-R3-derived tier (R9), with the rest of severity/progression the remaining lift.
Sections
- §1Classification, burden, and treatment frameworkthree axes + deterministic burden index + residual offset + grade legend · grade [H]
- #1Achondrogenesis type IIskeletal disease in COL2A1; residual burden rank 1/23 · grade [H]
- #2Niemann-Pick disease, type Alysosomal disease in SMPD1; residual burden rank 2/23 · grade [H]
- #3Becker muscular dystrophymusculoskeletal disease in DMD; residual burden rank 3/23 · grade [H]
- #4alpha Thalassemiahematologic disease in HBA1, HBA2; residual burden rank 4/23 · grade [H]
- #5Achondroplasiaskeletal disease in FGFR3; residual burden rank 5/23 · grade [H]
- #6Duchenne muscular dystrophymusculoskeletal disease in DMD; residual burden rank 6/23 · grade [H]
- #7Fabry diseaselysosomal disease in GLA; residual burden rank 7/23 · grade [H]
- #8Osteogenesis imperfectaskeletal disease in COL1A1, COL1A2; residual burden rank 8/23 · grade [H]
- #9Tyrosinemia type Ihepatic/metabolic disease in FAH; residual burden rank 9/23 · grade [H]
- #10Glycogen storage disease, type IImetabolic/muscular disease in GAA; residual burden rank 10/23 · grade [H]
- #11Polycystic kidney disease 2renal disease in PKD2; residual burden rank 11/23 · grade [H]
- #12Classic homocystinuriametabolic disease in CBS; residual burden rank 12/23 · grade [H]
- #13Hurler syndromelysosomal disease in IDUA; residual burden rank 13/23 · grade [H]
- #14Hereditary factor VIII deficiency diseasehematologic disease in F8; residual burden rank 14/23 · grade [H]
- #15Maple syrup urine diseasemetabolic disease in BCKDHA, BCKDHB; residual burden rank 15/23 · grade [H]
- #16Phenylketonuriametabolic disease in PAH; residual burden rank 16/23 · grade [H]
- #17Cystic fibrosisrespiratory/exocrine disease in CFTR, FCGR2A, TGFB1; residual burden rank 17/23 · grade [H]
- #18Gaucher disease type Ilysosomal disease in GBA1; residual burden rank 18/23 · grade [H]
- #19Tyrosinemia type IImetabolic disease in TAT; residual burden rank 19/23 · grade [H]
- #20Hereditary factor IX deficiency diseasehematologic disease in F9; residual burden rank 20/23 · grade [H]
- #21Gaucher diseaselysosomal disease in (gene not annotated at this aggregate concept); residual burden rank 21/23 · grade [H]
- #22Marfan syndromeconnective_tissue disease in FBN1; residual burden rank 22/23 · grade [H]
- #23Beta-thalassemia HBB/LCRBhematologic disease in HBB, HBB-LCR; residual burden rank 23/23 · grade [H]
- np21-Hydroxylase-Deficient Congenital Adrenal Hyperplasiaendocrine disease in CYP21A2; not placed (2/5 axes scored) · grade [O]
- npAcute intermittent porphyriametabolic disease in HMBS; not placed (2/5 axes scored) · grade [O]
- npAlpha-1-antitrypsin deficiencyhepatic/respiratory disease in SERPINA1; not placed (2/5 axes scored) · grade [O]
- npHb SS diseasehematologic disease in HBB; not placed (2/5 axes scored) · grade [O]
- npHemochromatosis type 1hepatic/metabolic disease in BMP2, HFE; not placed (2/5 axes scored) · grade [O]
- npWilson diseasehepatic/metabolic disease in ATP7B; not placed (2/5 axes scored) · grade [O]
- npAlkaptonuriametabolic disease in HGD; not placed (1/5 axes scored) · grade [O]
- npCystinosisrenal/lysosomal disease in CTNS; not placed (1/5 axes scored) · grade [O]
- npCystinuriarenal disease in SLC3A1, SLC7A9; not placed (1/5 axes scored) · grade [O]
- npEhlers-Danlos syndrome, classic type, 1connective_tissue disease in COL5A1; not placed (1/5 axes scored) · grade [O]
- npEhlers-Danlos syndrome, type 4connective_tissue disease in COL3A1; not placed (1/5 axes scored) · grade [O]
- npvon Willebrand disease type 1hematologic disease in VWF; not placed (1/5 axes scored) · grade [O]
- [F]Lysosomal storage and transport disordersmechanism class linking 7 member disease pages · grade [F]
- [F]Fibrillar collagenopathiesmechanism class linking 4 member disease pages · grade [F]
23 diseases are placed in the rankable order (≥ 3 of 5 burden axes scored); 12 further diseases are listed as not placed (fewer than three axes scored, rank null, open axes graded [O] not guessed), each still on its own page. 2 cross-cutting mechanism chapters (lysosomal storage; fibrillar collagenopathies) link their member disease pages without restating them. The systemic cohort has no repeat-expansion disease — those are neurological, owned by the sibling neuro volume.