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: Skeletal disease in transfusion-dependent thalassemia is commonly attributed to reduced bone mineral density and managed with anti-resorptive therapy. However, chronic iron overload can induce progressive endocrine siderosis, disrupting anabolic pathways essential for bone homeostasis. This mechanism remains under-recognized and may underlie treatment failure in severe cases. Case: We describe a 34-year-old female with transfusiondependent HbE β-thalassemia, post-splenectomy, receiving regular transfusions and iron chelation, who sustained multiple pathological fractures following a trivial fall, including bilateral supracondylar femur fractures and a distal radius fracture. She had severe systemic iron overload (ferritin 2,621 ng/mL) complicated by hepatic cirrhosis, insulin-dependent diabetes, and hypogonadotropic hypogonadism. Bone mineral density assessment demonstrated severe osteoporosis (hip T-score −5.4) despite prolonged bisphosphonate therapy, with prior vertebral compression fracture. Endocrine evaluation revealed multiaxis dysfunction, including gonadal failure and probable growth hormone deficiency, consistent with pituitary and peripheral endocrine siderosis. Conclusion This case demonstrates that skeletal fragility in transfusiondependent thalassemia reflects an endocrine-driven failure of bone formation rather than isolated loss of bone mineral density. Iron overload–induced endocrine siderosis impairs osteoblast function and suppresses anabolic signaling, leading to profound skeletal vulnerability. The progression of osteoporosis despite anti-resorptive therapy highlights the limitation of conventional approaches and supports reframing thalassemia-associated bone disease as an endocrine disorder. Severe osteoporosis should prompt systematic endocrine evaluation, with early hormonal replacement and consideration of anabolic therapy to prevent catastrophic fractures and long-term disability.
Siderosis ; Thalassemia

Introduction: Thalassemia is a hemoglobin synthesis disorder associated with chronic anemia and transfusion-related iron overload, which predisposes patients to multiple endocrine complications. Iron deposition in the pituitary and gonads may result in growth hormone deficiency (GHD) and hypogonadism. Empty sella syndrome (ESS), characterized by herniation of the subarachnoid space into the sella turcica, may also contribute to hypopituitarism. The coexistence of thalassemia-related endocrinopathies, ESS, and autoimmune thyroid disease is rare and presents significant diagnostic complexity. Case: A 27-year-old female with transfusion-dependent thalassemia on deferiprone presented with secondary amenorrhea and short stature. Her height was 145 cm (below the target range of 140.5–157.5 cm), body mass index 17.3 kg/m², and Tanner stage M3P1. Laboratory evaluation revealed elevated thyroidstimulating hormone (10.92 mIU/L) with low-normal free thyroxine 4 (11.4 pmol/L), consistent with primary hypothyroidism. Thyroid ultrasound demonstrated features of chronic thyroiditis, and anti-thyroid peroxidase antibodies (8.18 IU/mL) supported a diagnosis of Hashimoto’s thyroiditis. Insulin-like growth factor-1 was markedly reduced (68 ng/mL), indicating GHD. Morning cortisol was within normal range (14.5 µg/dL). Gonadotropins were inappropriately low-normal (folliclestimulating hormone 7.42 mIU/mL, luteinizing hormone 11.41 mIU/mL) with low estradiol (26.49 pg/mL), suggesting hypogonadotropic hypogonadism. Skeletal survey showed thalassemia-related bone changes, including trabecular coarsening and metaphyseal widening, with a predicted adult height of 142.7 cm. Pituitary magnetic resonance imaging revealed an empty sella. Conclusion Thalassemia must be recognized not only as a primary hematologic condition but also as a complex multisystem disorder with profound endocrine implications. Furthermore, the co-occurrence of these conditions with rare manifestations such as ESS and Hashimoto’s thyroiditis underscores the diagnostic complexity faced by clinicians. Therefore, early detection and rigorous, regular endocrine screening are essential to optimize management strategies and improve the long-term quality of life for patients with thalassemia.
Empty Sella Syndrome ; Growth Hormone ; Thalassemia ; Thyroiditis

Introduction: Adolescence is a crucial period for achieving peak bone mass. Risk factors such as chronic inflammation, endocrine issues, corticosteroid use, and extended immobility can lead to severe secondary osteoporosis and fragility fractures. Case: A 15-year-old female with transfusion-dependent thalassemia had been hospitalized for over a year following severe acute gastroenteritis complicated by septic shock, multiorgan failure, and secondary hemophagocytic lymphohistiocytosis (HLH). She received pulse methylprednisolone therapy for HLH, which was tapered over 6 months. Her clinical course was further complicated by critical illness polyneuropathy and post-infectious bronchiectasis, leading to ventilator dependence and a bedbound state. During regular physiotherapy sessions, she developed a sudden onset of severe left shoulder pain. A radiograph of the left shoulder revealed a closed fracture of the humeral neck. Biochemical evaluation showed normal serum calcium and phosphate levels, adequate vitamin D status, and normal alkaline phosphatase levels. However, follicle-stimulating hormone, luteinizing hormone (LH), and estradiol levels were undetectable, consistent with arrested puberty due to chronic illness. A bone mineral density scan showed a lumbar spine Z-score of −6, indicating severe osteoporosis. She was started on intravenous zoledronate for secondary osteoporosis, and physiotherapy was resumed to improve musculoskeletal strength. Conclusion This patient was treated with bisphosphonate therapy for severe secondary osteoporosis caused by multiple risk factors, including chronic illness, prolonged immobility, corticosteroid use, and hypogonadotropic hypogonadism, with limited potential for spontaneous bone recovery. This case highlights the importance of early endocrine monitoring and bone health assessments to identify impaired bone growth and prevent fragility fractures in high-risk adolescents.
Adolescent ; Humans ; Chronic Disease ; Thalassemia

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