Diamond Blackfan Anemia / Congenital Hypoplastic Anemia

Rare, bone marrow failure syndrome, 90% cases diagnosed in 1st yr of life.

 

Etiology

  • Ribosomal protein gene mutations 40S / 60S subunits (RPS19-40S ribosomal subunit)- 70%cases - ...therefore often called ribosomopathy
  • GATA1 - X.L.R

Clinical Manifestations

  • profund anemia evident by 2-6mo
  • Congenial anomalies
    • craniofacial - 50%
    • skeletal- 30%

LocationAnomalies
Craniofacial
  • Hypertelorism
  • Broad,flat nasal bridge
  • Cleft Palate
  • High arched palate
  • Microcephaly
  • Microtia
  • Micrognathia
  • Low set ears
  • Low hairline
  • Ptosis
Ophthalmic
  • Congenital glaucoma
  • Strabismus
  • Epicanthal folds
  • Congenital cataract
Neck
  • Short, webbed neck
  • Sprengel deformity
  • klippel feil deformity
Thumb
  • Triphalangeal, duplex,bifid
  • hypolastic
  • Flat thenar eminence
  • absent radial artery
Urogenital
  • Absent kidney
  • Horseshoe kidney
  • Hypospadias
Cardiac
  • VSD, ASD
    • Coarctation of aorta
  • Complex heart ds
Other
  • Low birth weight
  • Short stature
  • Syndactyly
  • Learning difficulties

Lab

  • RBC- macrocytic,↑ Hb F,↑ "i" antigen, no other features of megaloblastic anemia
  • ↑Erythrocyte adenosine deaminase(eADA)
  • ↓ Reticulocytes(erythrocyte prescursors)
  • ↑ S.Iron

D.D

  • Transient erythroblastopenia of childhood
  • Fanconi anemia
  • Shwachman Diamond syndrome
  • Myelodysplastic syndrome
  • Aase syndrome
  • HDNB-aplastic crisis
  • parvovirus B19
  • Pearson syndrome

Treatment

  • Chronic transfusion therapy upto 1 year age.(∵early corticosteroid impair physical & neurocognitive development)
  • then, initiate Prednisolone 2mg/kg/day
    • 1-3wks:↑ B.M erythrocyte precursor
    • 4-6wks: Hb normalises
  • when response +ve, Gradually taper till single lowest daily dose, then double the dose & use alternate day.(target maintenance: < 1mg/kg/altday)
  • pneumocystis prophylaxis after 1mo high dose corticosteroid
  • 35% remain unresponsive- transfusions required.
  • rx with l-leucine is promising.
  • HSCT is curative, best results,if done under 9yre age with HLA matched sibling donor.(ensure donor is DBA gene free)

Prognosis

it is known as cancer predisposition syndrome

  • myelodysplastic synd.
  • AML
  • Colonic ca.
  • Osteogenic sarcoma
  • female genital cancer
Iron overload related endocrinal abn.
  • diabetes
  • hypogonadism
Survival rate: @40yrs 87% if maintained on CS theray, 57% if transfusion dependent