Biallelic hypomorphic variants in CAD cause uridine-responsive macrocytic anaemia with elevated haemoglobin-A2.

Autor: Steinberg-Shemer O; Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.; Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Yacobovich J; Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.; Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Noy-Lotan S; Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel., Dgany O; Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel., Krasnov T; Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel., Barg A; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel., Landau YE; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Metabolic Disease Service, Schneider Children's Medical Center of Israel, Petach Tikva, Israel., Kneller K; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel., Somech R; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel., Gilad O; Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Brik Simon D; Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel., Orenstein N; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel., Izraeli S; Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Del Caño-Ochoa F; Structure of Macromolecular Targets Unit, Instituto de Biomedicina de Valencia (IBV), CSIC, Valencia, Spain., Tamary H; Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.; Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Ramón-Maiques S; Structure of Macromolecular Targets Unit, Instituto de Biomedicina de Valencia (IBV), CSIC, Valencia, Spain.; Group 739, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)-Instituto de Salud Carlos III, Valencia, Spain.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2024 Mar; Vol. 204 (3), pp. 1067-1071. Date of Electronic Publication: 2023 Nov 20.
DOI: 10.1111/bjh.19215
Abstrakt: 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.
(© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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