Clinical Course of Homozygous Hemoglobin Constant Spring in Pediatric Patients

Komvilaisak, Patcharee; Jetsrisuparb, Arunee; Fucharoen, Goonnapa; Komwilaisak, Ratana; Jirapradittha, Junya; Kiatchoosakun, Pakaphan

doi:10.1097/mph.0000000000001160

Cited by 8 publications

(8 citation statements)

References 11 publications

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“…On the other hand, red cells hemolysis in Hb Constant Spring is maybe because of precipitation and aggregation of mRNAs that affecting the red cell membrane and producing visible basophilic stippling 30 .…”

Section: Discussionmentioning

confidence: 99%

Genotype–phenotype correlation in patients with deletional and nondeletional mutations of Hb H disease in Southwest of Iran

Hamid

Keikhaei

Galehdari

et al. 2022

Sci Rep

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We studied the alpha-globin gene genotypes, hematologic values, and transfusion-dependence of patients with Hb H disease. Molecular characterization of alpha-thalassemia was performed. We identified 120 patients with Hb H disease. Of these patients, 35 (29.16%) had deletional form of Hb H disease, and 85 (70.83%) had different form of non-deletional Hb H disease. The most frequently observed Hb H genotypes were --Med/–α3.7 in 33 patients (27.5%), αCD19(-G) α/αCD19(-G) α in 25 cases (20.83%), αpolyA2α/αpolyA2α in 15 (12.5%), and αpolyA1α/αpolyA1α in 13 (10.83%) respectively. The probability of receiving at least one transfusion blood in deletional form was observed in 3 of 35 (8.57%) patients which just seen in 3 of 33 (9%) patients with --Med/–α3.7 genotype. This form was also observed in 8 of 85 (9.4%) patients in non-deletional Hb H diseases which five of them had Med deletion in compound with alpha globin point mutations. Nondeletional Hb H disease was more severe than deletional Hb H disease requiring more blood transfusions. We can recommend that Med deletion in compound with alpha-globin point mutations, polyA1 and constant spring in homozygous form needs to be taken into consideration when offering counseling to high-risk couples.

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Section: Discussionmentioning

confidence: 99%

Genotype–phenotype correlation in patients with deletional and nondeletional mutations of Hb H disease in Southwest of Iran

Hamid

Keikhaei

Galehdari

et al. 2022

Sci Rep

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“…Hb CS is an abnormal Hb produced due to a mutation in the termination codon of HBA2 (18) and is the most common non-deletional mutation found in Southeast Asia. The mutation results in the insertion of glutamine in the stop codon that disrupts its function, leading to the production of elongated α-globin chains with additional 31 amino acid residues (2).…”

Section: Molecular Characterisation Of Common Non-deletional α-Thalas...mentioning

confidence: 99%

“…However, the clinical outcome varies, depending on age. A mild to severe anaemia may occur in children and adults, whereas neonatal jaundice can present in neonates (18). However, there was a reported case involving a neonate who was initially diagnosed with foetal anaemia, and later, developed signs of hydrops foetalis due to homozygous Hb CS (57).…”

Section: Haemoglobin Adanamentioning

confidence: 99%

Clinical and Haematological Parameters of Commonly Reported Non-deletional α-thalassaemia Mutations in Southeast Asia: A Review

Vijian¹,

Rahman²,

Kannan³

et al. 2022

MJMHS

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Alpha (α)-thalassaemia is a common genetic disorder worldwide caused by the deletion and rarely non-deletional mutations of the α-globin gene. Nearly 70 types of non-deletional mutations have been reported worldwide, and this review focuses on the common ones affecting α-thalassaemia patients. The common mutations are initiation codon mutation, codon 30, haemoglobin (Hb) Constant Spring, Hb Quang Sze, Hb Adana and Hb Evora. The haematological parameters of non-deletional mutations usually show mild changes. However, a severe reduction in haemoglobin level, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), and mean corpuscular haemoglobin count (MCHC) has been observed among compound heterozygous HbH disease, involving both deletional and non-deletional mutations. Although non-deletional mutations are rarely reported, it requires the study of more cases to understand the clinical phenotypes that lead to severe clinical manifestations.

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“…Haemoglobin-Constant Spring (Hb-CS, α142, Term→ Gln, TAA>CAA (α 2 ), α cs α/) is a nondeletional form of α-thalassemia (α-Thal) with a nucleotide substitution at the termination codon CD142 (UAA>CAA) of the α 2globin gene [1]. Although the heterozygote of Hb-CS is clinically normal, when associated with a 0 -thalassemia, it can result in HbH-CS disease (-/a CS a), which is the most common type of nondeletional HbH disease (β4) in southern China [2]. In addition, HbH-CS disease-affected individuals are usually more anaemic, more symptomatic, and more prone to significant hepatosplenomegaly, especially compared to an individual with a triple gene deletion involving the a-globin gene (-/-a), who is more likely to require transfusions [3].…”

Section: Introductionmentioning

confidence: 99%

CRISPR/Cas9 gene correction of HbH-CS thalassemia-induced pluripotent stem cells

Xie

Chen

et al. 2019

Ann Hematol

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Haemoglobin (Hb) H-constant spring (CS) alpha thalassaemia (-/-α CS) is the most common type of nondeletional Hb H disease in southern China. The CRISPR/Cas9-based gene correction of patient-specific induced pluripotent stem cells (iPSCs) and cell transplantation now represent a therapeutic solution for this genetic disease. We designed primers for the target sites using CRISPR/Cas9 to specifically edit the HBA2 gene with an Hb-CS mutation. After applying a correction-specific PCR assay to purify the corrected clones followed by sequencing to confirm the mutation correction, we verified that the purified clones retained full pluripotency and exhibited a normal karyotype. This strategy may be promising in the future, although it is far from representing a solution for the treatment of HbH-CS thalassemia now.

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Clinical Course of Homozygous Hemoglobin Constant Spring in Pediatric Patients

Cited by 8 publications

References 11 publications

Genotype–phenotype correlation in patients with deletional and nondeletional mutations of Hb H disease in Southwest of Iran

Genotype–phenotype correlation in patients with deletional and nondeletional mutations of Hb H disease in Southwest of Iran

Clinical and Haematological Parameters of Commonly Reported Non-deletional α-thalassaemia Mutations in Southeast Asia: A Review

CRISPR/Cas9 gene correction of HbH-CS thalassemia-induced pluripotent stem cells

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