Transfusion Independence Achieved in a Case of Diamond Blackfan Anaemia by Essential Amino Acid Supplementation

Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome usually presenting as pure red cell aplasia in the first few months of life, which can be associated with systemic features like short stature, skeletal, cardiac and renal abnormalities, and has an increased risk of aplasia and malignancy. The genetic defect is now known in 50% of the cases affecting ribosomal proteins and although the pathophysiological mechanism has not been elucidated, it is known that they have inefficient translation, which a recent report suggests that in some cases can be overcome by leucine supplementation both in vitro and in vivo.

We report an 8 years old boy diagnosed at 2 years of age with an Hb 3.4 g/dL requiring monthly blood transfusions. During the first year following the diagnosis he received trials of both steroids and ciclosporin, which he failed to respond to and remained transfusion dependent at the same frequency. At 3 years and 10 months of age the parents sought the advice of a nutritionist because his height was below the 2^nd centile (92 cm) and weight in the 9^th centile (13.9 kg). High performance liquid chromatography measurement of amino acids in blood revealed deficiency of isoleucin 40 μM (NR >44) and threonine 34 μM (NR >31). He received an essential aminoacid supplementation formula containing the following daily amounts: L-5-Hydroxytryptophan 0.01669 g/day, L-Arginine 0.3373 g/day, L-Histidine 0.3625 g/day, L-Isoleucine 0.6043 g/day, L-Leucine 0.6964 g/day, L-Lysine 0.3539 g/day, L-Methionine 0.5265 g/day, L-Phenylalanine 0.4628 g/day, L-Taurine 0.1669 g/day, L-Threonine 0.4908 g/day, L-Valine 0.6652 g/day, Pyridoxal-5-phosphate 0.0106 g/day, Alpha-ketoglutaric acid 0.3049 g/day. Six months after the initiation of the essential amino acid supplementation the interval between transfusions started to become longer and he became transfusion independent at 12 months. The Hb has increased steadily from 10 g/dL to 13.6 g/dL. His height has steadily improved to the 9^th centile and the weight to the 25^th–50^th centile.

Whilst we cannot exclude that this child may have entered into spontaneous remission as it is known to happen in 5–10% of the patients with DBA, this case supports the recent report that essential amino acid supplementation may overcome the terminal differentiation defects found in the erythropoiesis of patients with DBA. A controlled trial of essential amino acid supplementation is warranted in patients with DBA.