title: An Unusual Hydrops Fetalis Associated with Compound Heterozygosity for Krüppel-like Factor 1 mutations.
abstract: Hydrops fetalis is commonly due to Hb Bart's (γ4) disease in South East Asia. Here, we report an unusual case of hydrops fetalis due to congenital dyserythropoietic anemia (CDA) associated with compound heterozygosity for Krüppel-like factor 1 (KLF1) gene mutations. Fetal cardiomegaly was first detected on routine mid-trimester scan in a pregnant woman with normal mean corpuscular volume (MCV) and Rhesus positive status. The fetus subsequently developed hydrops fetalis, and cordocentesis showed severe fetal anemia with a hemoglobin (Hb) level of 3.4 g/dL. Common causes of fetal anemia including Hb Bart's disease, parvovirus infection, and red cell antibodies were excluded. In view of the marked increase in erythroblasts at various stages of erythropoiesis, the diagnosis of CDA was suspected. We screened the couple for previously reported KLF1 gene mutations, showing that the mother was heterozygous for the c.525_526insCGGCGCC, p.Gly176Argfs*179 mutation, and her husband heterozygous for c.1012C>A, p.Pro338Thr mutation. The fetus was a compound heterozygote for these two KLF1 mutations. After counseling, repeated intrauterine transfusions were given at 27, 29, and 34 weeks' gestation; the hydrops fetalis was resolved. The baby was delivered at 34 weeks' gestation and required monthly blood transfusions but was otherwise thriving. Bone marrow aspiration at 10 months of age showed the features of ineffective erythropoiesis, compatible with CDA. In conclusion, hydrops fetalis can rarely be due to CDA associated with a compound heterozygous mutation for KLF1 gene mutations, and be managed by repeated intrauterine transfusions. Our present report adds to the wide clinical spectrum of KLF1 mutations.
authors.affiliation: a Department of Obstetrics and Gynaecology , Queen Elizabeth Hospital , Hong Kong SAR , People's Republic of China.
authors.forename: Helena H L
authors.initials: HH
authors.lastname: Lee
authors.affiliation: a Department of Obstetrics and Gynaecology , Queen Elizabeth Hospital , Hong Kong SAR , People's Republic of China.
authors.forename: Annisa S L
authors.initials: AS
authors.lastname: Mak
authors.affiliation: a Department of Obstetrics and Gynaecology , Queen Elizabeth Hospital , Hong Kong SAR , People's Republic of China.
authors.forename: K O
authors.initials: KO
authors.lastname: Kou
authors.affiliation: a Department of Obstetrics and Gynaecology , Queen Elizabeth Hospital , Hong Kong SAR , People's Republic of China.
authors.forename: C F
authors.initials: CF
authors.lastname: Poon
authors.affiliation: b Department of Clinical Pathology , Queen Elizabeth Hospital , Hong Kong SAR , People's Republic of China.
authors.forename: W S
authors.initials: WS
authors.lastname: Wong
authors.affiliation: c Department of Paediatrics , Queen Elizabeth Hospital , Hong Kong SAR , People's Republic of China.
authors.forename: K H
authors.initials: KH
authors.lastname: Chiu
authors.affiliation: d Prenatal Diagnostic Laboratory, Department of Obstetrics and Gynaecology, Tsan Yuk Hospital , The University of Hong Kong , Hong Kong SAR , People's Republic of China.
authors.forename: Patrick K C
authors.initials: PK
authors.lastname: Au
authors.affiliation: d Prenatal Diagnostic Laboratory, Department of Obstetrics and Gynaecology, Tsan Yuk Hospital , The University of Hong Kong , Hong Kong SAR , People's Republic of China.
authors.forename: Kelvin Y K
authors.initials: KY
authors.lastname: Chan
authors.affiliation: d Prenatal Diagnostic Laboratory, Department of Obstetrics and Gynaecology, Tsan Yuk Hospital , The University of Hong Kong , Hong Kong SAR , People's Republic of China.
authors.forename: Anita S Y
authors.initials: AS
authors.lastname: Kan
authors.affiliation: d Prenatal Diagnostic Laboratory, Department of Obstetrics and Gynaecology, Tsan Yuk Hospital , The University of Hong Kong , Hong Kong SAR , People's Republic of China.
authors.forename: Mary H Y
authors.initials: MH
authors.lastname: Tang
authors.affiliation: a Department of Obstetrics and Gynaecology , Queen Elizabeth Hospital , Hong Kong SAR , People's Republic of China.
authors.forename: K Y
authors.initials: KY
authors.lastname: Leung
mesh_terms: D000328:Adult; D000742:Anemia, Dyserythropoietic, Congenital / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D001805:Blood Transfusion, Intrauterine; D001856:Bone Marrow Examination; D017218:Cordocentesis; D005260:Female; D006579:Heterozygote; D006801:Humans; D015160:Hydrops Fetalis / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D007223:Infant; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor
keywords: Congenital dyserythropoietic anemia; Krüppel-like factor 1 (KLF1) gene mutations; fetal anemia; hydrops fetalis; intrauterine transfusion