LATE PRESENTATION AND DIAGNOSIS OF DIAMOND BLACKFAN ANEMIA IN A
GREEK FAMILY
Polyxeni Delaporta1, Adrianna Vlachos2,3, Stavros Glentis4 and Antonis Kattamis1
(1)First Department of Pediatrics, National and Kapodistrian University of Athens, Aghia Sophia
Children's Hospital, Athens, Greece
(2)Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York
(3)Division of Hematology/Oncology and Cellular Therapy, Cohen Children’s Medical Center, Northwell
Health, New Hyde Park,, New York
(4)Pediatric Hematology/Oncology Unit (POHemU) First Department of Pediatrics University of
Athens, Aghia Sophia Children's Hospital, Athens, Greece
Background: Diamond Blackfan Anemia (DBA) is a rare congenital, bone marrow failure
syndrome characterized by normochromic macrocytic anemia, reticulocytopenia, absence or
paucity of erythroid precursors, short stature, congenital anomalies, and cancer
predisposition. The disease is associated with heterozygous mutations in one of 26 genes
encoding either a large or small subunit-associated ribosomal protein (RP) resulting in RP
haploinsufficiency. Apart from RP mutations, there are few cases of DBA caused by mutations
in X-linked genes encoding TSR2 and the erythroid transcription factor GATA1. The genetic
basis in around 25% of the cases remain elusive.
Case presentation: A 29 year old male was admitted to the hospital due to worsening anemia.
Blood analysis revealed macrocytic anemia (Hb 9.3 g/dL, MCV101.8 fl) with a low reticulocyte
count (RET: 0.4%) and increased HbF levels while bone marrow biopsy revealed severe
hypoplasia of the erythroid cell line with dysplastic abnormalities in megakaryocyte
precursors (PLT: 415 x10*9/L). Molecular analysis showed a heterozygous mutation (c. 124
C>T, p.Gln42Ter) of the RPL11 (NM_000975.5) gene which was inherited from his father. This
mutation has also been previously described in a patient with DBA. The patient, the first child
of the family, was born at 40 weeks gestation to non-consanguineous Greek parents. He has
bilateral triphalangeal thumbs without other somatic malformations. At the age of 2 years he
was diagnosed with tuberculosis infection and he received appropriate treatment for 12
months. During childhood mild normochromic normocytic (MCV 89 fl) anemia was noted with
hemoglobin levels between 10-11 g/dL. Hypothyroidism was diagnosed at the age of 19 years.
At the age of 26 years he presented with ventricular extrasystole arrhythmia and he was
treated with catheter ablation. For the anemia of DBA at age 29 years, the patient received
treatment with prednisolone, to which he responded very well, reaching a Hb of 12.9 g/dL
with minimal steroid dose of 0.06 mg/kg/day.
The father of the patient was also noted to have bilateral triphalangeal thumbs and
hexadactyly. The father has mild normochromic macrocytic (MCV 95 fl) anemia Hb 12.3g/dl.
At the age of 46 years he presented with a right ocular melanoma without hepatic metastases,
for which he received radiation therapy.
Conclusions: The phenotypic spectrum of DBA shows significant heterogeneity, even within
the same families. Phenotypes can range from individuals with classical features to individuals
with solitary somatic malformations. Our cases show late hematologic presentation with
unique features, namely ventricular extrasystole and occurrence of ocular melanoma in adult
patients with previously undiagnosed DBA. Late presentation of DBA, especially in adults with
anemia and congenital anomalies, must be considered for optimal diagnosis, intervention and
guidance.
POSTER 11
SCIENTIFIC PROGRAMME
SESSION I
BONE MARROW
RESPONSE TO VIRAL
INFECTIONS
SESSION II
HAEMATOLOGICAL
RESPONSE TO SARS
COV2 INFECTION
SESSION III
DYSERYTHROPOIESIS IN
CLONAL HAEMOPOIESIS
AND MDS
SESSION IV
ERYTHROPOIESIS
CONTROL
SESSION V
ERYTHROPOIESIS
CONTROL : PHASE 2
SESSION VI
IRON METABOLISM
AND ERYTHROPOIESIS
SESSION VII
INHERITED
DYSERYTHROPOIESIS
SESSION VIII
GENE THERAPY/EDITION
SESSION IX – DRUGS
AND INEFFECTIVE
ERYTHROPOIESIS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
FACULTY DISCLOSURES