Hb Bart's Hydrops Fetalis

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

ALG1, PMM2, THSD1, HBA2, ASAH1, HBA1, CCBE1, PIEZO1, GUSB, EPHB4, NEU1, AARS2, GBA, C1orf105, MYOM1, FZD6, UROS, TMEM151B, CARS2, GALNT14, CTSA, UBN1, PIGC, CHRNA1, NEB, COL1A1, LBR, COL1A2, CYP21A2, GATA1, SOX18, ACKR3, ADRA1A, COG6, ALG8, MIR195, ALG9, RPS19, CXCR6, CALCRL, LPAR2, THBS1, SSTR4, ADRA2B, RASA1, MGAT2, GPR42, EDNRA, BRS3, AFP, LOC111674464

Drugs

(S)-3'-(OH)-desazadesferrithiocin-polyether, magnesium salt, 4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methylthiazole-4(S)-carboxylic acid, Allogeneic multi-virus specific T lymphocytes targeting BK virus, cytomegalovirus, human herpesvirus-6, Epstein Barr virus and adenovirus, Deferasirox ( EXJADE, DEFERASIROX MYLAN ), Deferiprone ( FERRIPROX, DEFERIPRONE LIPOMED ), haematopoietic stem cells and blood progenitors umbilical cord-derived expanded with (1R, 4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine dihydrobromide dihydrate

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A rare, severe form of alpha-thalassemia that is almost always lethal. It is characterized by fetal onset of generalized edema, pleural and pericardial effusions, and severe hypochromic anemia.

Epidemiology

The disease occurs predominantly in Southeast Asia. Incidence in this region is estimated to be between 1/2,000 and 1/200 births. Exact incidence in other regions is not known.

Clinical description

Edema, signs of heart failure and profound intra-uterine anemia are the presenting features in the fetus. Other clinical features include marked hepatosplenomegaly, retardation in brain growth, hydrocephaly, urogenital and cardiovascular deformities, and extramedullary erythropoiesis. Maternal complications during pregnancy include preeclampsia, polyhydramnios or oligohydramnios, antepartum hemorrhage, and premature delivery. Early therapeutic termination of at-risk pregnancies is usually recommended due to the severity of the syndrome and the risk of potentially serious maternal complications during pregnancy.

Etiology

Bart's hydrops fetalis is caused by deletion or inactivation of all four alpha-globin alleles leading to a severe deficiency in alpha-globin chains of Hb, and to the production of gamma-4 tetramers (Hb Bart). Hb Bart tetramers have an extremely high oxygen affinity and are incapable of effective tissue oxygen delivery. The disease is the result of mutations in the HBA1 or HBA2 genes (16p13.3).

Diagnostic methods

The disease is usually diagnosed on ultrasound at 22 to 28 weeks gestation and can be suspected in at-risk pregnancies at 13 to 14 weeks gestation when increased nuchal or placental thickness, and increased cardiothoracic ratio are found.

Differential diagnosis

The main differential diagnosis is hydrops fetalis (see this term) without alpha-thalassemia, which is a common non-specific sign of numerous fetal or maternal disorders.

Antenatal diagnosis

Because of the risks for the fetus and for the mother, prenatal diagnosis for Hb Bart's should be offered.

Management and treatment

Death almost always occurs in utero or shortly after birth, although a very small number of patients survive following intra-uterine transfusions and repeated frequent transfusions after birth. Treatment is controversial since treated infants surviving the immediate postnatal period show abnormal subsequent development. These patients may be considered for hematopoietic stem cell transplantation.

Prognosis

Most surviving infants experience a complicated perinatal course and a high prevalence of congenital urogenital and limb defects.