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X-linked sideroblastic anaemia in a female fetus: a case report and a literature review

BACKGROUND: X-linked sideroblastic anaemia (XLSA) is commonly due to mutations in the ALAS2 gene and predominantly affects hemizygous males. Heterozygous female carriers of the ALAS2 gene mutation are often asymptomatic or only mildly anaemic. XLSA is usually characterized by microcytic erythrocytes...

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Autores principales: Nzelu, Diane, Shangaris, Panicos, Story, Lisa, Smith, Frances, Piyasena, Chinthika, Alamelu, Jayanthi, Elmakky, Amira, Pelidis, Maria, Mayhew, Rachel, Sankaran, Srividhya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686580/
https://www.ncbi.nlm.nih.gov/pubmed/34930268
http://dx.doi.org/10.1186/s12920-021-01146-z
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author Nzelu, Diane
Shangaris, Panicos
Story, Lisa
Smith, Frances
Piyasena, Chinthika
Alamelu, Jayanthi
Elmakky, Amira
Pelidis, Maria
Mayhew, Rachel
Sankaran, Srividhya
author_facet Nzelu, Diane
Shangaris, Panicos
Story, Lisa
Smith, Frances
Piyasena, Chinthika
Alamelu, Jayanthi
Elmakky, Amira
Pelidis, Maria
Mayhew, Rachel
Sankaran, Srividhya
author_sort Nzelu, Diane
collection PubMed
description BACKGROUND: X-linked sideroblastic anaemia (XLSA) is commonly due to mutations in the ALAS2 gene and predominantly affects hemizygous males. Heterozygous female carriers of the ALAS2 gene mutation are often asymptomatic or only mildly anaemic. XLSA is usually characterized by microcytic erythrocytes (reduced mean corpuscular volume (MCV)) and hypochromia, along with increased red cell distribution width. However, in females with XLSA the characteristic laboratory findings can be dimorphic and present with macrocytic (elevated MCV) in addition to microcytic red cells. CASE PRESENTATION: We report a case of fetal anaemia, presenting in the early third trimester of pregnancy, in a female fetus. Ultrasound findings at 29 weeks were of cardiomegaly, prominent umbilical veins, a small rim of ascites, and mean cerebral artery peak systolic velocity (PSV) value above 1.5 Multiples of the Median (MoM). She underwent non-invasive prenatal testing that determined the rhesus genotype of the fetus to be rhesus B negative. No red blood cell antibodies were reported. Other investigations to determine the underlying cause of fetal anaemia included microarray comparative genomic hybridization, serology to exclude congenital infection and a peripheral blood film and fetal bilirubin to detect haemolysis. The maternal grandmother had a history of sideroblastic anaemia diagnosed at the age of 17 years. The mother had mild macrocytic anaemia with haemoglobin of 10.4 g/dl and MCV of 104 fl. The fetal anaemia was successfully treated with two in utero transfusions (IUTs), and delivery occurred via caesarean section at 37 weeks of gestation. The red cell gene sequencing in both the mother and fetus were heterozygous for an ALAS2 mutation causing in utero manifestations of XLSA. The haemoglobin on discharge to the local hospital at five days of age was 19.1 g/dl. Subsequently, the infant became anaemic, requiring regular 3–4 monthly blood transfusions and demonstrating overall normal development. Her anaemia was unresponsive to pyridoxine. CONCLUSIONS: This is one of four cases reporting multiple female members presenting with discordant clinical features of XLSA from being entirely asymptomatic to hydropic in utero. Our report is novel in that there are no previous cases in the literature of anaemia in a female fetus heterozygous for ALAS2 mutation.
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spelling pubmed-86865802021-12-20 X-linked sideroblastic anaemia in a female fetus: a case report and a literature review Nzelu, Diane Shangaris, Panicos Story, Lisa Smith, Frances Piyasena, Chinthika Alamelu, Jayanthi Elmakky, Amira Pelidis, Maria Mayhew, Rachel Sankaran, Srividhya BMC Med Genomics Case Report BACKGROUND: X-linked sideroblastic anaemia (XLSA) is commonly due to mutations in the ALAS2 gene and predominantly affects hemizygous males. Heterozygous female carriers of the ALAS2 gene mutation are often asymptomatic or only mildly anaemic. XLSA is usually characterized by microcytic erythrocytes (reduced mean corpuscular volume (MCV)) and hypochromia, along with increased red cell distribution width. However, in females with XLSA the characteristic laboratory findings can be dimorphic and present with macrocytic (elevated MCV) in addition to microcytic red cells. CASE PRESENTATION: We report a case of fetal anaemia, presenting in the early third trimester of pregnancy, in a female fetus. Ultrasound findings at 29 weeks were of cardiomegaly, prominent umbilical veins, a small rim of ascites, and mean cerebral artery peak systolic velocity (PSV) value above 1.5 Multiples of the Median (MoM). She underwent non-invasive prenatal testing that determined the rhesus genotype of the fetus to be rhesus B negative. No red blood cell antibodies were reported. Other investigations to determine the underlying cause of fetal anaemia included microarray comparative genomic hybridization, serology to exclude congenital infection and a peripheral blood film and fetal bilirubin to detect haemolysis. The maternal grandmother had a history of sideroblastic anaemia diagnosed at the age of 17 years. The mother had mild macrocytic anaemia with haemoglobin of 10.4 g/dl and MCV of 104 fl. The fetal anaemia was successfully treated with two in utero transfusions (IUTs), and delivery occurred via caesarean section at 37 weeks of gestation. The red cell gene sequencing in both the mother and fetus were heterozygous for an ALAS2 mutation causing in utero manifestations of XLSA. The haemoglobin on discharge to the local hospital at five days of age was 19.1 g/dl. Subsequently, the infant became anaemic, requiring regular 3–4 monthly blood transfusions and demonstrating overall normal development. Her anaemia was unresponsive to pyridoxine. CONCLUSIONS: This is one of four cases reporting multiple female members presenting with discordant clinical features of XLSA from being entirely asymptomatic to hydropic in utero. Our report is novel in that there are no previous cases in the literature of anaemia in a female fetus heterozygous for ALAS2 mutation. BioMed Central 2021-12-20 /pmc/articles/PMC8686580/ /pubmed/34930268 http://dx.doi.org/10.1186/s12920-021-01146-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Case Report
Nzelu, Diane
Shangaris, Panicos
Story, Lisa
Smith, Frances
Piyasena, Chinthika
Alamelu, Jayanthi
Elmakky, Amira
Pelidis, Maria
Mayhew, Rachel
Sankaran, Srividhya
X-linked sideroblastic anaemia in a female fetus: a case report and a literature review
title X-linked sideroblastic anaemia in a female fetus: a case report and a literature review
title_full X-linked sideroblastic anaemia in a female fetus: a case report and a literature review
title_fullStr X-linked sideroblastic anaemia in a female fetus: a case report and a literature review
title_full_unstemmed X-linked sideroblastic anaemia in a female fetus: a case report and a literature review
title_short X-linked sideroblastic anaemia in a female fetus: a case report and a literature review
title_sort x-linked sideroblastic anaemia in a female fetus: a case report and a literature review
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686580/
https://www.ncbi.nlm.nih.gov/pubmed/34930268
http://dx.doi.org/10.1186/s12920-021-01146-z
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