Marrow Failure Syndromes

Transient Erythroblastopenia of Childhood

• Temporary peripheral reticulocytopenia: anemia with normal WBC and platelet lines
• Male and female incidence about even
• 80% present at age > 1 year (versus Diamond-Blackfan anemia's 15% at > 1 year); 10% present after 3 years of age.
• About half are preceeded by a viral infection.
• Presenting Hgb usually about 6, with reticulocytes of about 1% and normal MCV.
• BM demonstrates erythroblastopenia.
• No increase in adenine deaminase (as is seen in Diamond-Blackfan anemia)
• Natural History: Usually recover within 1-2 months of diagnosis.
• Treatment
• Observe.
• Transfuse only if cardiovascularly unstable.
• No steroids.

Shwachman-Diamond Anemia

• Neutropenia with exocrine pancreatic insufficiency
• Presents with malabsorbtion, steattorhea, FTT, skin infection, pneumonia
• Inheritance is autosomal recessive.
• Diagnostic tests:
• Decreased duodenal trypsin (like Fanconi Anemia)
• Decreased duodenal lipase and amylase (unlike Fanconi Anemia)
• Negative sweat test
• Bone marrow findings
• Decreased to normal cellularity
• Myeloid line normal or arrested
• Erythroid line normal or increased
• Treatment
• Antibiotics
• Transfusions
• Consider GCSF
• ? Steroids

Diamond-Blackfan Anemia

• Usually presents in infancy, 90% by one year of age
• Both dominant and recessive patterns
• Physical Exam: Often flattened thenar eminence, weak radial pulse, triphalangeal thumbs
• Lab Findings:
• Normochromic, macrocytic more often than normocytic
• Persistent fetal hemoglobin, persistence of i-antigen on RBC membrane
• Serum Fe, ferritin, folic acid, B12 and erythropoetin increased
• DAT negative
• Adenosine deaminase often increased (unlike TEC)
• Bone marrow
• Normocellular with selective deficiency of RBC precursors
• Myeloid line normal to decreased
• Megakaryocytes normal to increased
• Normal Chromosomes
• Treatment
• Transfusions: Leuko-depleted pRBCs q 3-6 weeks to keep Hgb > 6 g/dL
• Side effect is hemosiderosis (possible diabetes, liver failure, growth abnormalities, failure to enter puberty, etc.)
• Steroids
• 2 mg/kg/day divided tid-qid
• Reticulocytes increase in one to two weeks.  Continue until Hgb > 10 g/dL then wean.
• Stem Cell Transplant
• Splenectomy has no effect on DBA

Pearson Syndrome

• Rare
• Clinical presentation: malabsorbtion, FTT
• Characterized by metabolic acidosis and anemia
• Maternal inheritance
• Mitochondrial DNA deletion
• Variable size, encompasses mtDNA encoding oxidative phosphorylation enzymes and some mt-tRNAs
• Lab findings
• Macrocytic anemia
• ANC < 1000 cells/uL in about 50%
• Bone Marrow: Vacuolated erythroid and myeloid precursors
• On stain, (ringed) sideroblasts
• Natural History
• May outgrow transfusion dependent
• Death is from acidosis, sepsis, liver or renal failure
• Some develop Kearns-Sayre Syndrome (ophthalmoplegia, pigmentary retinopathy, ataxia, heart block)