TY - JOUR
T1 - Biallelic hypomorphic variants in CAD cause uridine-responsive macrocytic anaemia with elevated haemoglobin-A2
AU - Steinberg-Shemer, Orna
AU - Yacobovich, Joanne
AU - Noy-Lotan, Sharon
AU - Dgany, Orly
AU - Krasnov, Tanya
AU - Barg, Assaf
AU - Landau, Yuval E.
AU - Kneller, Katya
AU - Somech, Raz
AU - Gilad, Oded
AU - Brik Simon, Dafna
AU - Orenstein, Naama
AU - Izraeli, Shai
AU - del Caño-Ochoa, Francisco
AU - Tamary, Hannah
AU - Ramón-Maiques, Santiago
N1 - Publisher Copyright:
© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
PY - 2024/3
Y1 - 2024/3
N2 - Biallelic pathogenic variants in CAD, that encode the multienzymatic protein required for de-novo pyrimidine biosynthesis, cause early infantile epileptic encephalopathy-50. This rare disease, characterized by developmental delay, intractable seizures and anaemia, is amenable to treatment with uridine. We present a patient with macrocytic anaemia, elevated haemoglobin-A2 levels, anisocytosis, poikilocytosis and target cells in the blood smear, and mild developmental delay. A next-generation sequencing panel revealed biallelic variants in CAD. Functional studies did not support complete abrogation of protein function; however, the patient responded to uridine supplement. We conclude that biallelic hypomorphic CAD variants may cause a primarily haematological phenotype.
AB - Biallelic pathogenic variants in CAD, that encode the multienzymatic protein required for de-novo pyrimidine biosynthesis, cause early infantile epileptic encephalopathy-50. This rare disease, characterized by developmental delay, intractable seizures and anaemia, is amenable to treatment with uridine. We present a patient with macrocytic anaemia, elevated haemoglobin-A2 levels, anisocytosis, poikilocytosis and target cells in the blood smear, and mild developmental delay. A next-generation sequencing panel revealed biallelic variants in CAD. Functional studies did not support complete abrogation of protein function; however, the patient responded to uridine supplement. We conclude that biallelic hypomorphic CAD variants may cause a primarily haematological phenotype.
KW - anaemia
KW - genetic disorders
KW - haemoglobin
KW - paediatric
UR - http://www.scopus.com/inward/record.url?scp=85177241215&partnerID=8YFLogxK
U2 - 10.1111/bjh.19215
DO - 10.1111/bjh.19215
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C2 - 37984840
AN - SCOPUS:85177241215
SN - 0007-1048
VL - 204
SP - 1067
EP - 1071
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -