Clinical Summary

Sydney is a 4 year old white female. She was born term after an uncomplicated pregnancy and delivery to a 31 year old G1P0 via spontaneous vaginal delivery. BW 2887gms. APGAR'S 8/9. Parents are healthy with no significant past history. (I have evaluated CBC and blood smears of both parents and they are normal). No family history of thalassemia or CDA. Union is non-consanguineous. Sydney was born here in Orlando . There was no BART'S Hb present on neonatal screening. Both Sydney and mother are blood group O POS. Direct COOMBS NEG.

Sydney was a vigorous healthy appearing neonate but developed jaundice in the first 24 hours of life. She received antibiotics but there was no real set up for sepsis or hemolysis. Physical exam was normal.

Initial labs were:

She received triple phototherapy. The highest bilirubin was 20.3 mg/dl on day of life 2(DOL). Working diagnosis at the time was hyperbilirubinemia likely secondary to a congenital hemolytic process possibly due to a RBC enzyme defect.

Sydney continued to be stable and active and hyperbilirubinemia responded to phototherapy. However during the first week of life her Hb and reticulocyte count continued to fall. By DOL9 her Hb had fallen to 7.3 g/dl with reticulocyte count 4.9% and absolute 116 and RBC 2.37. WBC and platelets normal. She was subsequently transfused PRBC. G6PD and Pyruvate kinase enzyme levels were performed prior to transfusion and were normal.

Sydney, now 4 years old has remained transfusion dependent since her first transfusion on DOL9. She requires PRBC transfusions every 3-4 weeks. Her Hb is maintained at 8-9g/dl. She has also remained reticulocytopenic. Average pre transfusion absolute reticulocyte count is 20-40. This reticulocytopenia persist even with Hb as low as 5g/dl. There has been no evidence for hemolysis since the early neonatal period.

She has had 3 BM evaluations 9/04 ,3/05 and 7/07 ages 4 months,10 months and 3 years. The first BM had marked erythroid hyperplasia with a M:E ratio of 1:15.Otherwise trilineage hematopoiesis with no erythroid dysplasia. The subsequent 2 BM's had normal ME ratio and no dysplasia. Serum RBC enzyme studies, RBC ADA and Hb electrophoresis have all been normal, Erythropoietin level 26IU/ml (normal 4-24), RPS19 mutation negative .However all these investigations were performed while Sydney was being transfused.

Clinically Sydney has splenomegaly that developed since 2 years old and is stable at 4cm below the left costal margin. There is no other abnormal clinical findings. She is a charming and affable young girl that is developmentally normal and thriving appropriately.There is no laboratory evidence for hemolysis and her other cell lines are normal.

In summary Sydney is a 4 year old girl with splenomegaly, congenital anemia and reticulocytopenia and with essentially normal BM morphology. A variant of DBA with primarily ineffective erythropoiesis seem likely. However splenomegaly suggest extramedullary hematopoiesis suggesting a globin chain synthetic disorder The next investigation I think would be useful is reticulocyte (or BM) alpha/beta globin synthetic ratio and reticulocyte ADA level.

Sydney has been a challenge diagnostically. She tolerates monthly PRBC transfusions well an is on iron chelation therapy. Advise on the use of steroids or splenomegaly would be useful.


Respectfully,

Paul Gordon, MD

07/2008