OBJECTIVE: To explore the efficacy of a Thalassemia risk assessment software for the screening of thalassemia mutation carriers and distribution of thalassemia genotypes detected by screening. METHODS: A total of 6 040 individuals were evaluated at Leshan Maternal and Child Health Care Hospital between 2022 and 2024 using the commonly used clinical thalassemia risk assessment method and the thalassemia screening software, respectively, and the performance indicators of the two methods were compared and analyzed against the result of thalassemia gene testing. This study was approved by the Ethics Committee of our hospital (Ethics No.: LfyLL[2022]005). RESULTS: The high-risk rate by the thalassemia screening software was 11.19%, with a sensitivity of 95.12%, specificity of 93.28%, positive predictive value of 43.20%, negative predictive value of 99.72%, and the area under the ROC curve (AUC) was 0.942. The thalassemia gene detection rate of the high-risk samples screened was 4.83%. The high-risk screening rate of the conventional method was 2.50%, with a sensitivity of 51.22%, specificity of 93.28%, positive predictive value of 80.79%, negative predictive value of 97.40%, and the AUC was 0.754. The thalassemia gene detection rate of the high-risk samples was 2.02%. CONCLUSION The software can effectively detect thalassemia carriers and significantly reduce the missed detection compared with conventional method, thereby significantly improve the efficacy of screening.
Humans ; Thalassemia/diagnosis* ; Software ; Female ; Genetic Testing/methods* ; Male ; Mutation ; Adult ; Genotype ; ROC Curve ; Risk Assessment

INTRODUCTION: Elevated troponin, while essential for diagnosing myocardial infarction, can also be present in non-myocardial infarction conditions. The myocardial-ischaemic-injury-index (MI3) algorithm is a machine learning algorithm that considers age, sex and cardiac troponin I (TnI) results to risk-stratify patients for type 1 myocardial infarction. METHOD: Patients aged ≥25 years who presented to the emergency department (ED) of Singapore General Hospital with symptoms suggestive of acute coronary syndrome with no diagnostic 12-lead electrocardiogram (ECG) changes were included. Participants had serial ECGs and high-sensitivity troponin assays performed at 0, 2 and 7 hours. The primary outcome was the adjudicated diagnosis of type 1 myocardial infarction at 30 days. We compared the performance of MI3 in predicting the primary outcome with the European Society of Cardiology (ESC) 0/2-hour algorithm as well as the 99th percentile upper reference limit (URL) for TnI. RESULTS: There were 1351 patients included (66.7% male, mean age 56 years), 902 (66.8%) of whom had only 0-hour troponin results and 449 (33.2%) with serial (both 0 and 2-hour) troponin results available. MI3 ruled out type 1 myocardial infarction with a higher sensitivity (98.9, 95% confidence interval [CI] 93.4-99.9%) and similar negative predictive value (NPV) 99.8% (95% CI 98.6-100%) as compared to the ESC strategy. The 99th percentile cut-off strategy had the lowest sensitivity, specificity, positive predictive value and NPV. CONCLUSION The MI3 algorithm was accurate in risk stratifying ED patients for myocardial infarction. The 99th percentile URL cut-off was the least accurate in ruling in and out myocardial infarction compared to the other strategies.
Humans ; Male ; Female ; Emergency Service, Hospital ; Middle Aged ; Electrocardiography ; Machine Learning ; Singapore ; Chest Pain/blood* ; Troponin I/blood* ; Myocardial Infarction/blood* ; Risk Assessment/methods* ; Aged ; Algorithms ; Acute Coronary Syndrome/blood* ; Adult ; Sensitivity and Specificity

Consensus ; Humans ; Child ; Thalassemia/therapy* ; Disease Management ; Pediatrics/standards* ; China/epidemiology* ; Blood Transfusion

Iron overload is a major complication of thalassemia, clinically manifested as heart failure, liver cirrhosis, diabetes, growth and development retardation, and delayed sexual development, with severe cases leading to death. Standardized iron chelation therapy is essential to ensure long-term and high-quality survival for patients. This guideline provides recommendations on methods for detecting iron overload, the timing for initiating iron chelation therapy, treatment strategies for transfusion-dependent and non-transfusion-dependent thalassemia, and special circumstances regarding iron chelation therapy, serving as a reference for iron chelation treatment in thalassemia.
Humans ; Thalassemia/drug therapy* ; Iron Chelating Agents/therapeutic use* ; Iron Overload/diagnosis* ; Chelation Therapy

Transfusion-dependent thalassemia (TDT) is a severe genetic chronic hemolytic disease, and growth retardation is a common clinical feature in patients with TDT. Due to the need for regular blood transfusions, these patients often experience iron overload, which leads to various endocrine dysfunctions, including abnormalities in the growth hormone/insulin-like growth factor axis, hypothyroidism, hypoparathyroidism, hypogonadism, adrenal insufficiency, and decreased bone density. This paper reviews the clinical monitoring and intervention measures for growth disorders and related endocrine functions in patients with TDT, providing references for clinicians.
Humans ; Thalassemia/physiopathology* ; Child ; Growth Disorders/diagnosis* ; Blood Transfusion ; Endocrine System Diseases/therapy*

Thalassemia is a group of hereditary disorders characterized by ineffective erythropoiesis due to hemoglobin synthesis abnormalities, resulting in varying degrees of chronic anemia. Patients with transfusion-dependent thalassemia rely on lifelong regular blood transfusions and iron chelation therapy. Proper transfusion treatment and management of transfusion-related complications are essential to ensure the growth and development of pediatric patients and to improve their quality of life. The guideline working group has developed the guideline by referencing domestic and international guidelines, expert consensus, and relevant studies. The aim is to further standardize the transfusion management of transfusion-dependent thalassemia in children in China.
Humans ; Thalassemia/therapy* ; Blood Transfusion/standards* ; Child ; East Asian People

OBJECTIVE: To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia. METHODS: A retrospective study was conducted on 7 patients diagnosed by Yangjiang People's Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People's Hospital of Yangjiang (Ethics No: 20240001). RESULTS: For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A2, whilst another had significantly decreased Hb A and Hb A2, in addition with the appearance of a Hb H band. The content of Hb Bart's in four neonates was ≥ 0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c.2delT, HBA2: c.1A>G, HBA2: c.1A>T, and HBA1: c.2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c.427T>C (Hb CS) and HBA2: c.2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c.1A>G and Southeast Asian type deletion. CONCLUSION Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c.1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.
Humans ; Phenotype ; Codon, Initiator/genetics* ; Female ; Male ; Retrospective Studies ; alpha-Globins/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobin A/genetics* ; Adult ; Mutation

OBJECTIVE: To analyze the hematological characteristics of patients with three common deletional β-thalassemia and concomitant α-thalassemia in Huizhou, Guangdong province. METHODS: A total of 1 335 subjects of childbearing age with hemoglobin F (Hb F) ≥ 5% at the Huizhou First Maternal and Child Health Care Hospital between June 2014 and December 2023 were enrolled as our study cohort. The hematological parameters were determined by blood cell counters and automatic capillary electrophoresis, while liquid phase chip and gap-PCR were employed for the detection of routine thalassemias and the three common deletional β-thalassemia, respectively. The hematological characteristics of patients with the deletional β-thalassemia were analyzed. This study was reviewed and approved by the Ethics Committee of Huizhou First Maternal and Child Health Care Hospital [Ethics No. 20231107(B2)]. RESULTS: A total of 384 cases of the three common deletional β-thalassemia were identified, including 184 cases of Chinese Gγ⁺(Aγδβ)⁰, 191 cases of Southeast Asian hereditary persistence of fetal hemoglobin (SEA-HPFH), and nine cases of Chinese Taiwanese, for a total detection rate of 28.76%. Patients who did not meet the established criteria were excluded from the study, leaving 372 cases. All of which presented with hypochromic microcytic anemia and significantly elevated Hb F. Except for normal or decreasing of Hb A2 levels in patients with Chinese Gγ⁺(Aγδβ)⁰, the levels of Hb A2 in patients with the other two deletional β-thalassemia were increased with different degrees. Differential comparison results showed that significant differences were observed in Hb A2 and Hb F values among the groups of the three common deletional β-thalassemia heterozygotes (P < 0.05). According to the type of gene variation, 180 patients with Chinese Gγ⁺(Aγδβ)⁰ heterozygotes were divided into three groups, including αα/αα, Chinese Gγ⁺(Aγδβ)⁰/β^N (149), -α/αα, Chinese Gγ⁺(Aγδβ)⁰/β^N (14), and --/αα, Chinese Gγ⁺(Aγδβ)⁰/β^N (17). Similarly, 179 patients with SEA-HPFH heterozygotes were divided into three groups, including αα/αα, SEA-HPFH/β^N (150), -α/αα, SEA-HPFH/β^N (12), and --/αα, SEA-HPFH/β^N (17). Differential comparison results showed that the Hb F levels of the Chinese Gγ⁺(Aγδβ)⁰ combined with α⁰-thalassemia group were significantly lower than those of the Chinese Gγ⁺(Aγδβ)⁰ combined with α⁺-thalassemia group and the control group (P < 0.05). The mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and Hb F values of the SEA-HPFH combined with α⁰-thalassemia group were significantly lower than those of the SEA-HPFH combined with α⁺-thalassemia group and the control group (P < 0.05). CONCLUSION The above research results can not only enhance the ability of clinicians to identify deletional β-thalassemia and concomitant α-thal, improve the level of genetic counseling, but also provide data support for the development of deletional β-thalassemia prevention and control programme and the development of prenatal and postnatal care.
Humans ; beta-Thalassemia/complications* ; alpha-Thalassemia/complications* ; Female ; China ; Male ; Adult ; Fetal Hemoglobin/genetics* ; Adolescent ; Young Adult

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a neonate with X-linked alpha-thalassemia mental retardation syndrome (ATR-X) caused by ATRX gene variant, and review related literature on children with ATR-X caused by ATRX gene variants. METHODS: A case of ATR-X neonate who was transferred to the First Affiliated Hospital of Zhengzhou University on February 11, 2022 for poor effect of treatment in the neonatology department of the hospital where he was born for 4 days due to "postnatal slow response, groaning, and cyanosis of the skin for 30 min" was selected as the study subject. 3 mL of peripheral blood was collected from the child and their parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used to verify the pathogenic gene variations in the child's family. The pathogenicity of genetic variant sites was assessed based on the Standards and Guidelines for the Interpretation of Sequence Variants by American College of Medical Genetics and Genomics (ACMG). The amino acid sequence conservation analysis of relevant variant proteins was conducted by the Universal Protein Resource Database (UniProt) and visual analysis of these variant proteins was performed by Swiss online protein three-dimensional modeling database (SWISS-MODEL). Using keywords such as "ATRX gene" and " X-linked alpha-thalassemia mental retardation syndrome" both in Chinese and English, relevant literature on ATR-X children caused by ATRX gene variants was retrieved from the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases, and the clinical phenotypes of ATR-X patients reported in the retrieved literature were analyzed. The literature retrieval time was set from the establishment of each database to December 31st, 2023. This study followed the research procedures approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-1360-002), and informed consent of clinical study was signed by the guardian of the child. RESULTS: The child in this study presented with symptoms such as delayed response, feeding difficulties accompanied by vomiting, low body temperature, hypotonia in all extremities, apnea, abnormal hearing screening, and a Neonatal Behavioral Neurological Assessment (NBNA) score of 19 (lower than the normal range).Hemoglobin (Hb) electrophoresis suggested the presence of α-thalassemia. The results of WES and Sanger sequencing revealed a hemizygous missense variant c.668G>A (p.C223Y) in exon 9 of the ATRX gene in the child of the study, neither of the parents of the child carried this variant, indicating that it is a de novo variant. Based on the Standards and Guidelines for the Interpretation of Sequence Variants released by ACMG, this gene variant was assessed as pathogenic (PS2+PM2_Supporting+PP3_Strong+PP4_Strong). The results of amino acid sequence analysis revealed that the pathogenic variant site normally encodes cysteine, which is highly conserved among various animal species. This pathogenic variant can lead to alterations in the hydrogen bonding structure of ATRX protein, thereby affecting its structural stability. Based on the clinical manifestations and genetic testing results of the child in this study, a diagnosis of ATR-X syndrome was established Based on the literature retrieval strategy established in this study, 13 relevant articles concerning ATR-X syndrome in children caused by ATRX gene variants were retrieved, including 5 Chinese articles and 8 English articles, involving a total of 311 ATR-X children. Including the child in this study, the total number of ATR-X children reaches 312. All 312 children were male and presented with mental retardation. Among them, 45.8% (143/312) had coexisting α-thalassemia, 45.2% (141/312) had abnormal genital appearance, 44.2% (138/312) had facial malformations, and 30.8% (96/312) had hypotonia. Other phenotypes included microcephaly, skeletal dysplasia, among others. CONCLUSION The ATR-X child in this study exhibit a range of clinical phenotypes, including delayed growth and development, facial malformation, abnormal genital appearance, apnea, vomiting symptoms, among others. The de novo variant of ATRX gene c.668G>A (p.C223Y) was identified as the genetic etiology. This study contributes to the expansion of the clinical phenotype spectrum and genetic variation spectrum of ATR-X children.
Humans ; X-linked Nuclear Protein/genetics* ; alpha-Thalassemia/genetics* ; X-Linked Intellectual Disability/genetics* ; Male ; Infant, Newborn ; Exome Sequencing ; Mutation

The 1985 version of WHO G6PD variation classification is no longer suitable for the development of modern medicine, and it has been revised by the WHO G6PD Technical Advisory Group. According to the genetic variation classification of G6PD by WHO in 2024, G6PD deficiency is divided into four categories: Class A: enzyme activity < 20% with chronic hemolytic anemia; Class B: enzyme activity < 45% in association with acute hemolysis caused by inducement; Class C: enzyme activity > 60%, no hemolysis; Class U: for those with incomplete clinical phenotypic information, and will be classified again with new clinical evidence obtained. The clinical implications of the new classification include: (1) To guide the prevention and treatment of G6PD deficiency; (2) To better understand the pathological and non-pathological status of G6PD deficiency, which lays a foundation for re-determining the birth defect rate in China; (3) To guide the safe use of anti-malarial drugs and related oxidizing drugs in G6PD deficient patients; (4) To promote the hierarchical health management of G6PD deficient individuals throughout their life cycle; (5) To guide the pathogenicity rating of G6PD gene variation; (6) To unify the diagnostic criteria for global G6PD deficiency, promote the homogenization, comparability and data sharing of global relevant data, and lay the foundation for the application of artificial intelligence.
Humans ; Glucosephosphate Dehydrogenase Deficiency/diagnosis* ; Glucosephosphate Dehydrogenase/genetics* ; Genetic Variation ; World Health Organization ; China