- incidence: rare (400 cases worldwide)
- age of onset:
- median: 2 months (M); 3 months (F)
- risk factors:
- most cases sporadic - i.e., new mutation
- familial in 10% of cases - autosomal recessive
- M > F (1.1:1)
PATHOGENESIS:
- considered to be one of at least 3 disorders where there
is a congenital deficiency in erythroid precursors
- other congenital single cytopenias:
- AASE Syndrome
- Congenital Dyserythropoietic Anemia
2. Genetic Defect
- genetic defect -> defective erythroid stem cells ->
decreased or absent BFU-E and CFU-E in bone marrow
- there may be a defect of the erythropoietin receptors on
erythroid stem cells
CLINICAL FEATURES:
- 10% of patients are severely anemia at birth while 90% are
severely anemic by 12 months of age
- pallor, lethargic, irritable, heart failure, death
2. Dysmorphic Features
- micro- or macrocephaly, micrognathia, macroglossia, wide
fontanelle
- tow coloured hair, snub nose, wide set eyes, thick upper
lip
2. Upper Limbs (10%)
- flattened thenar eminences +/- weak radial pulses
- abnormal thumbs - absent, bifid, subluxed,
supernumerary, triphalangeal
3. Ocular (7%)
- blue sclerae, cataracts, epicanthal folds, glaucoma,
hypertelorism, microphthalmos, strabismus
4. Renal (4%)
- absent, duplicated, or horseshoe kidneys
5. Others
- short stature, short or webbed neck
3. Complications
- due to multiple transfusions (>100)
- hepatosplenomegaly (hepatomegaly)
- leukopenia, thrombocytopenia
- short stature
- delayed puberty
- diabetes mellitus
- death in 2nd decade due to ischemic and siderotic
myo-cardial disease -> CHF
2. Neoplasms
- leukemia - ALL, AML
- thymomas
INVESTIGATIONS:
- Hb: macrocytic, normochromic, low reticulocytes
- high erythropoietin (also in urine)
- fetal characteristics of erythrocytes
- presence of fetal membrane antigen i
- increased HbF
- macrocytosis
- elevated serum iron, ferritin, folic acid, vit B12, RBC
adenosine deaminase activity (ADA)
- negative direct Coombs
- smear - macrocytes, anisocytosis, tear drops
- WBC - normal or slightly decreased
- PLT - normal or slightly increased
2. Bone Marrow
- normocellular with selective deficiency of RBC precursors:
- low number of BFU-E and CFU-E
- myeloid-erythroid ratio (10-200:1)
- erythroid hypoplasia or total aplasia (in 90% of cases)
- few pronormoblasts
- iron accumulation (after multiple transfusions)
MANAGEMENT:
- treatment of choice
- 2 mg/kg/d po tid or qid initially and then may increase
to
- 4-6 mg/kg/d
- reticulocytosis in 1-2 weeks
- normal Hb to normal levels by 4-6 wks
- gradually taper then alternate day therapy
- variable patterns of response - steroid nonresponders,
high-dose responders, and failures may make up 50% of cases
- side effects: growth retardation, osteoporosis, weight
gain, cushingoid appearance, hypertension, diabetes, fluid
retention, gastric ulcers, cataracts, glaucoma
2. RBC Transfusions
- indication: steroid-resistant patients (10% of cases)
- every 3-6 weeks
- side effects: transfusion reactions, AIDS, hepatitis,
alloantibody formation, hemosiderosis (treat with iron
chelating agent - subcutaneous desferrioxamine)
3. Bone Marrow Transplantation
- experimental for steroid-nonresponders
4. Prognosis
- 15-20% spontaneous remission rate
- steroid treatment improves survival with good quality of
life
- median survival age: 31 yrs (including non-responders)
|