EP21.11: A rare non‐immune cause of fetal anemia

A 29-year-old primigravida with low chance trisomy screening was seen in Fetal Medicine at 23 weeks of gestation with a pericardial effusion. The head and circumference were gestation appropriate but all the long bones, whilst normally calcified and straight were ≤ 5th centile. The structurally normal heart was enlarged with a pericardial effusion but good contractility. The hyperdynamic fetal circulation resulted in a peak systolic velocity in the middle cerebral artery >1.5MoMs. Infection screening was negative and an amniocentesis was performed. Fetal blood sampling at 23 weeks revealed a hemoglobin of 2.4g/l. A fetal transfusion of 33mls was given to raise this to 11.3g/l. Results showed a normal CGH array, no evidence of mevalonic aciduria and a negative Kleihauer. Given ongoing fetal anemia concerns a second transfusion was performed at 24 weeks, with further transfusions needed at 28 and 34 weeks of gestation. Whole-exome sequencing showed that both parents were carriers of CDAN1 gene variants. The baby was a compound heterozygote, consistent with a diagnosis of congenital dyserythropoietic anemia type 1. Delivery at 37 weeks of gestation resulted in a liveborn baby, needing phototherapy and subsequently required fortnightly transfusions with chelation. Pegylated interferon α2a was successfully started at one year of age to reduce transfusion frequency. MRI and neurological assessments showed no abnormalities. Congenital dyserythropoietic anemia type 1 is a rare autosomal recessive disorder characterised by ineffective erythropoiesis resulting in moderate-to-severe macrocytic anemia presenting occasionally in utero. More commonly it presents with intrauterine growth restriction and distal limb anomalies (4-14%). Most affected individuals have life-long moderate anemia, usually accompanied by jaundice and splenomegaly. Secondary hemochromatosis develops with age as a result of increased iron absorption even in those who are not transfused.