Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article is the first report of hemoglobin (Hb) Pyrgos along with other Hbs forming triple-heterozvgous patterns. Of 2 cases, the first occurred in a Thai girl with thalassemic facies, marked anemia, and hepatosplenomegaly, who had Hb Pyrgos in association with Hb H disease with Hb Constant Spring (CS). This case represents a triple heterozygosity comprising Hb Pyrgos, alpha-thalassemia 1, and Hb CS. Hb electrophoresis revealed an abnormal Hb in addition to Hbs CS, A2, A, Bart's, and H. This abnormal Hb moved slightly faster than Hb A but more slowly than Hb Bart's. Polymerase chain reaction revealed that the abnormal Hb was caused by a missense mutation within codon 83 of the beta-globin gene (GGC to GAC) resulting in a glycine-to-aspartic acid substitution, which corresponds to Hb Pyrgos. The patient required blood transfusions by the age of 3 years. A splenectomy was performed when she was 5 years old, after which her hematocrit level remained above 32%. The second case was the patient's older sister who was also triple heterozygous (Hb Pyrgos, E, and CS) but was healthy.
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PMID:Triple heterozygosity of a hemoglobin variant: hemoglobin Pyrgos with other hemoglobinopathies. 1184 88

A six-year-old boy was diagnosed with beta-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for beta-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD.
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PMID:Bone marrow transplantation for beta-thalassaemia major by an HLA-mismatched parent. 1204 3

In Vietnam, the carrier rate for beta-thalassemia varies from 1.5% to 25% depending on the ethnic groups of the population. The molecular basis of beta-thalassemia in South Vietnam was studied in 50 unrelated beta-thalassemia patients. Of these, 31 had beta-thalassemia/Hb E, 18 were homozygous for beta-thalassemia, and 1 carried the beta-thalassemia trait. The majority of the patients were Kinh, four were Chinese, and two were Kinh-Chinese. All had severe anemia and received blood transfusions regularly, every 1-3 months. Hepatosplenomegaly was found in all patients, and splenectomy had been done in six patients. Normal alpha-globin genotype (alpha alpha/alpha alpha) was found in all subjects. Reverse dot-blot hybridization using oligonucleotide probes specific for Southeast Asian mutations can detect beta-thalassemia in 60 chromosomes in addition to 31 chromosomes with beta(E) mutation. Excluding the beta(E) gene, six previously reported Thai and Chinese beta-thalassemia mutations were found, including codons 41/42 (-TCTT) 35.3%, codon 17 (A-->T) 25.0%, -28 (A-->G) 7.3%, codons 71/72 (+A) 7.3%, IVS-II nt 654 (C-->T) 7.3%, and IVS-I nt 1 (G-->T) 6.0%. The Vietnamese frameshift mutation at codon 95 (+A) was detected by ARMS in seven chromosomes (10.3%). DNA polymorphism of the beta-globin gene cluster carrying the codon 95 mutation was - + - - - - - + for (G)gamma/XmnI, epsilon/HincII, (G)gamma/HindIII, (A)gamma/HindIII, psi beta/HincII, 3' psi beta/HincII, beta/AvaII, and 3'beta/BamHI, respectively. The remaining mutation detected by the gap PCR was a large deletion known as the Chinese (G)gamma((A)gamma delta beta)(0)-thalassemia. The two most common mutations were the frameshift at codons 41/42 (-TCTT) and the nonsense mutation in codon 17 (A-->T). Thus beta-thalassemia mutations in South Vietnam is similar to the previous report from the North, although at different frequencies. This result will help to establish a center for prenatal diagnosis and for prevention and control of thalassemia in Vietnam.
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PMID:Molecular analysis of beta-thalassemia in South Vietnam. 1235 5

We report a case of 12-year old Thai girl suffering from mild non-transfusion-dependent thalassemia intermedia. She is the single child in her family. On examination she looked pale; there was no hepatosplenomegaly. The Hb concentration was 9 g/dL. Hb typing and molecular mutation study revealed compound heterozygosity for HbE and Hb Leiden (alpha2beta26/7-Glu, codon 6/7-GAG). The proportion of HbE was 47% whereas that of Hb Leiden was 39%. The patient had no HbA. Hb typing of her father and mother revealed HbE trait, and no Hb Leiden was demonstrated. As the paternity test confirmed the parenthood, we assume that Hb Leiden has arisen by spontaneous mutation. A study of the beta< or= -globin gene framework by molecular cloning and subsequent DNA sequencing of the beta-globin gene in the members of the family indicated that the Hb Leiden mutation occurred on a maternal inherited chromosome. The deletion of codon 6 or 7 (-GAG) of the beta-globin gene in the patient may be due to an unequal crossing over during the mother's oogenesis.
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PMID:Spontaneous mutation of the hemoglobin Leiden (beta 6 or 7 Glu-->0) in a Thai girl. 1468 8

Sickle-beta(+) (beta(+)) thalassemia is a double heterozygous genetic disorder characterized by both a qualitative and quantitative abnormality. We present a case of an African American male who was first diagnosed with sickle cell disease (SCD) at the age 23 years when he presented with generalized bone pain, fever, and hepatosplenomegaly. Laboratory findings included thrombocytopenia, microcytic anemia, and markedly elevated ferritin. He was subsequently diagnosed with a sickle-beta thalassemia hemoglobinopathy. Findings in the bone marrow aspirate and biopsy were consistent with hemophagocytic lymphohistiocytosis (HLH). HLH resolved with the resolution of sickle cell bone pain crisis without use of immunosuppressive therapy. To the best of our knowledge this is the first documented case of HLH associated with sickle cell bone pain crisis.
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PMID:Sickle cell crisis associated with hemophagocytic lymphohistiocytosis. 1549 57

We report on a Thai female patient who presented with hypochromic microcytic anemia, hepatosplenomegaly, and failure to thrive since 3 years of age. Hematological and hemoglobin (Hb) analysis were consistent with a clinical diagnosis of Hb H disease. However, no abnormal Hb fraction had ever been detected. During the 20 years of follow-up, this patient experienced several episodes of hemolytic crisis, which worsened her anemia, necessitating blood transfusion. Recently, we identified Hb Quong Sze (Hb QS), a highly unstable globin gene mutation affecting codon 125 (CTG-->CCG) of alpha(2) globin gene in trans with the commonest alpha(0) thalassemia (-(SEA)) in the patient. This report highlights the clinical significance of Hb QS in Southeast Asians, as previously almost all of the patients described with this variant were of Chinese origin.
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PMID:Hemoglobin H disease induced by the common SEA deletion and the rare hemoglobin Quong Sze in a Thai female: longitudinal clinical course, molecular characterization, and development of a PCR/RFLP-based detection method. 1750 46

The thalassemias are inherited disorders resulting from deficient synthesis of one or more polypeptide chains of normal haemoglobin. There are two main groups of thalassemia: alpha and more common beta. The carriage of thalassemia genes are widely spread and the disease is considered the most common genetic disorder worldwide. Thalassemias are particularly prevalent in inhabitants of Italy, Greece, Spain, Mediterranean Islands, West Africa and some parts of Asia. The most common thalassemia beta cases are characterized from asymptomatic to severe microcytic anaemia with hepatosplenomegaly and physical development disturbances. The authors present eight unrelated children from the Pomerania Region of Poland complaining of chronic microcytic anaemia with normal iron level. Elevated level of haemoglobin A2 and in some of them haemoglobin F revealed thalassemia beta.
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PMID:[Thalassemia beta in children from Pomerania Region]. 1796 68

Mutations of the human SLC4A1 gene encoding erythroid and kidney isoforms of anion exchanger 1 (AE1, band 3) result in erythrocyte abnormalities or distal renal tubular acidosis (dRTA) and such mutations are observed in Southeast Asia, where hemoglobinopathies are prevalent. Genetic and hematological studies in 18 Thai patients with dRTA have shown that 12 of them (67%) carried SLC4A1 mutations (7 G701D/G701D, 3 SAO/G701D, and 2 G701D/A858D). Of these 12 patients, three had homozygous G701D/G701D and heterozygous Hb E; one compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia; and one compound heterozygous G701D/A858D and heterozygous Hb E. Of 6 patients without SLC4A1 mutation, two each carried heterozygous or homozygous Hb E and one of the latter also had Hb H disease (--(SEA)/-alpha(4.2)). The blood smears of patients with homozygous G701D/G701D showed approximately 25% ovalocytes. Strikingly, the patients with coexistence of homozygous G701D/G701D and heterozygous Hb E had 58% ovalocytes. Similarly, the patients who had compound heterozygous SAO/G701D showed 49% ovalocytes, but the patient with coexistence of compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia had 70% ovalocytes. Our previous study has shown that under metabolic acidosis, the patients with homozygous G701D/G701D or compound heterozygous SAO/G701D had reticulocytosis, indicating compensated hemolysis. A patient with compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia presented with hemolytic anemia and hepatosplenomegaly which was alleviated by alkaline therapy. Taken together, the coexistence of both homozygous or compound heterozygous SLC4A1 mutations and hemoglobinopathy has a combined effect on red cell morphology and degree of hemolytic anemia, which is aggravated by acidosis.
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PMID:Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies. 1826 5

The Lepore hemoglobins (Hbs) are a group of structural defects resulting from different recombination events between the delta- and beta-globin genes. They may come with different beta-thalassemia (beta-thal) minor-like phenotypes in the carrier and with variably severe phenotypes in the rare homozygote, and in the common compound heterozygote with beta-thal. The most seriously affected patients are those of Yugoslavian origin presenting with severe transfusion-dependent hemolytic anemia, dyserythropoiesis, hepatosplenomegaly and skeletal malformations. Because of genetic risk, couples where both partners are carriers of these combinations may require prognosis and prenatal diagnosis. In these cases, recognition of the defect must be done with particular care. We report a case of Hb Lepore induced by a yet unknown crossover event found in a 24-year-old Turkish male and compare the novel mutation with those previously reported.
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PMID:Hb Lepore-Leiden: a new delta/beta rearrangement associated with a beta-thalassemia minor phenotype. 1893 69

Fever of unclear origin is a clinical challenge in medical practice. Infectious diseases, neoplasms, and collagen vascular illnesses are its main causes in adults and children. Acute splenic sequestration crises, a known potentially fatal complication of sickle cell disease and sickle beta-thalassemia, are uncommon in beta-heterozygosis. We describe a case of prolonged recurrent episodes of fever with spontaneous resolution, commencing at age 10 in a 15-year-old boy with a history of hypochromic microcytic anemia attributed to a thalassemic trait. He was admitted twice to our university hospital for continuous-remittent fever with a pruritic, macular evanescent Still's skin rash, severe splenomegaly, leucopenia, thrombocytopenia, and sudden aggravation of anemia. Infectious, rheumatologic, autoimmune, and hematologic illnesses were excluded. A genetic-based study revealed heterozygosis of the beta-globin gene for a A>C (Thr>Pro) substitution at position 87 called Hemoglobin Valletta (alpha 2 beta 2 87 PRO) with a C>G transition in homozygosis in beta-globin intronic polymorphism intervening sequence 2 at nucleotide 745. After a follow-up period of 1 year without treatment, the young patient remains apyretic and in good general clinical health with persistent microcythemia and hepatosplenomegaly. Acute splenic sequestration crisis and related cytopenia may be an unusual complication of fever of unclear origin in a beta-thalassemic carrier of a Hemoglobin Valletta mutation and polymorphism in homozygosis of intervening sequence 2 at nucleotide 745. This hemoglobinopathy may predispose to a clinical phenotype of minor or intermediate thalassemia and, during a febrile illness, to hemoglobin instability and splenic sequestration.
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PMID:Fever of unclear origin and cytopenia because of acute splenic sequestration in a young immunocompetent carrier of beta-globin mutation for Hb Valletta. 1909 26


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