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Journal of Thrombosis and Haemostasis :... Nov 2013GFI1B is a transcription factor important for erythropoiesis and megakaryocyte development but previously unknown to be associated with human disease.
BACKGROUND
GFI1B is a transcription factor important for erythropoiesis and megakaryocyte development but previously unknown to be associated with human disease.
METHODS
A family with a novel bleeding disorder was identified and characterized. Genetic linkage analysis and massively parallel sequencing were used to localize the mutation causing the disease phenotype on chromosome 9. Functional studies were then performed in megakaryocytic cell lines to determine the biological effects of the mutant transcript.
RESULTS
We have identified a family with an autosomal dominant bleeding disorder associated with macrothrombocytopenia, red cell anisopoikilocytosis, and platelet dysfunction. The severity of bleeding is variable with some affected individuals experiencing spontaneous bleeding while other family members exhibit only abnormal bleeding with surgery. A single nucleotide insertion was identified in GFI1B that predicts a frameshift mutation in the fifth zinc finger DNA-binding domain. This mutation alters the transcriptional activity of the protein, resulting in a reduction in platelet α-granule content and aberrant expression of key platelet proteins.
CONCLUSIONS
GFI1B mutation represents a novel human bleeding disorder, and the described phenotype identifies GFI1B as a critical regulator of platelet shape, number, and function.
Topics: Adult; Aged; Aged, 80 and over; Blood Platelet Disorders; Blood Platelets; Erythrocytes; Female; Frameshift Mutation; Genetic Linkage; Humans; Male; Megakaryocytes; Middle Aged; Mutation; Phenotype; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins; Repressor Proteins; Sequence Analysis, DNA; Transfection; Young Adult
PubMed: 23927492
DOI: 10.1111/jth.12368 -
European Journal of Haematology May 2023Thalassemias are common monogenic autosomal recessive hemoglobin disorders. The usually asymptomatic heterozygotes (β-thalassemia traits, βTT) may rarely develop...
INTRODUCTION
Thalassemias are common monogenic autosomal recessive hemoglobin disorders. The usually asymptomatic heterozygotes (β-thalassemia traits, βTT) may rarely develop non-transfusion-dependent-thalassemia (NTDT) due to co-inheritance of supernumerary α-globin genes. Literature on phenotypic/genotypic features of these rare combinations is limited.
MATERIALS AND METHODS
We studied the demographic, clinical, and laboratory data from 47 persons with co-inherited βTT + supernumerary α-globin genes. HBB mutations were tested for by ARMS-PCR and/or Sanger sequencing, ααα /ααα and deletional α-thalassemia testing by multiplex gap-PCRs, and Xmn1 γ genotyping by PCR-RFLP.
RESULTS
The 47 cases comprised 0.08% of 61 010 hemoglobinopathy screenings during the study period. Mean age was 31.9 ± 14.7 years (range 5.5-83 years), with 57.4% males. Thirty (63.8%) had NTDT-phenotype, 16 (34%) were asymptomatic/minimally symptomatic, and 1 became transfusion-dependent at the age of 20 years. Anemia/pallor and jaundice were the commonest complaints (76% each); 40% had required blood transfusions. Twenty-one had splenomegaly, 14 had hepatomegaly. Mean hemoglobin was 9.0 ± 1.9 g/dl (range 4.0-13.0). HbA2 was 5.1 ± 0.7% (3.4%-6.3%) and HbF% 4.2 ± 3.2% (0.5%-18.4%). Forty-four (93.6%) had ααα , while 3 (6.4%) had ααα triplications. HBB:c.92+5G>C (47%), HBB:c.27_28insG (14.9%), and HBB:c.47G>A (8.5%) were the commonest β-globin mutations. One case showed HBB:c.-138C>T (β ), while the rest had β or severe-β mutations. Symptomatic cases had significantly lower hemoglobins and higher HbF% than asymptomatic ones.
CONCLUSION
This largest Indian and globally second-largest study reports the βTT + ααα state for the first time in such genotypically-complex Indian cases. Supernumerary α-genes should be suspected in all βTT with disproportionate clinical symptoms, mild-to-moderately elevated HbF, and unexplained anisopoikilocytosis.
Topics: Male; Female; Humans; beta-Thalassemia; alpha-Globins; Genetic Profile; Hemoglobinopathies; Mutation; beta-Globins
PubMed: 36598439
DOI: 10.1111/ejh.13923 -
La Tunisie Medicale Dec 2017- Hemoglobin C is a hemoglobin variant encountered worldwide. The regionswith high prevalence are West Africa and South-East Asia.The objective of this study is to...
BACKGROUND
- Hemoglobin C is a hemoglobin variant encountered worldwide. The regionswith high prevalence are West Africa and South-East Asia.The objective of this study is to report cases of hemoglobin C disease brought together during these last twelve years in the Laboratory of Biochemistry and Toxicology of RabatMilitary Hospital Mohammed V (MHIMV).
METHODS
- This was a retrospective study including111 cases of hemoglobin C disease collected in the Laboratory of Biochemistry of the MHIMVover the past 12 years. A questionnairewasfulfilledwith the epidemiological data,clinical data and the results of the biological explorations. The screening of the hemoglobin variant in this study included several biochemical (hemoglobin electrophoresis at acid and alkalinepH) and hematological tests.
RESULTS
- Sex-ratio was equal to 1,22. The age at the time of diagnosis ranges between 4 and 80years old, with the mean of 38. North-West regions of Morocco seem most affected. The most frequent reasons for prescription of the hemoglobin's studywere: biological abnormalities, splenomegaly and anemic syndrome. Blood smear reveals frequently anisopoikilocytosis and red blood target. The biochemical tests contribute to the diagnosis and reveal various and varied etiological groups: heterozygous A/C (75%),homozygous C/C (8%), double heterozygous S/C (9%),C/β+-thal (6%) andC/O-Arab (2%). Conclusion - The results of the present descriptive study are in line with the literature data. The importance of genetic counseling and the installation of a national card of systematic neonatal tracking seemto be unavoidable.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Protein Electrophoresis; Child; Child, Preschool; Cohort Studies; Female; Genetic Testing; Hematologic Tests; Hemoglobin C; Hemoglobin C Disease; Humans; Male; Middle Aged; Morocco; Retrospective Studies; Young Adult
PubMed: 29878289
DOI: No ID Found -
Frontiers in Pharmacology 2020We present two unrelated Chinese patients with CAD deficiency manifesting with a triad of infantile-onset psychomotor developmental delay with regression,...
We present two unrelated Chinese patients with CAD deficiency manifesting with a triad of infantile-onset psychomotor developmental delay with regression, drug-refractory epilepsy, and anaemia with anisopoikilocytosis. Timely translation into uridine supplementation, within 2-months of disease onset, allowed us to stop conventional anti-epileptic drugs and led to dramatic improvement in the clinical symptoms, with prompt cessation of seizures, resolution of anaemia, developmental progress, and prevention of development of severe and non-reversible manifestations. The remarkable recovery and prevention of advanced disease with prompt treatment, highlights the need to act immediately upon genetic diagnosis of a treatable disease. This further reinforces CAD deficiency as a treatable neurometabolic disorder and emphasises the need for a biomarker or genetic new born screening for early identification.
PubMed: 33364968
DOI: 10.3389/fphar.2020.608737 -
Leukoerythroblastosis in a Young Child with Severe Malaria and Superimposed Gram Negative Infection.Journal of Tropical Pediatrics Dec 2018Leukoerythroblastosis, a non-specific and often short-lasting response of the bone marrow to different diseases such as malignancies or infections, is characterized by...
BACKGROUND
Leukoerythroblastosis, a non-specific and often short-lasting response of the bone marrow to different diseases such as malignancies or infections, is characterized by the presence in the peripheral blood of immature red and white cells.
METHODS
We present a case of leukoerythoblastosis occurring in a 24 months old Mozambican girl, in the context of a severe malaria episode and an associated urinary tract infection. Peripheral blood smear was used for diagnosis of malaria and leukoerythroblastosis. Enterobacter cloacae isolation and antibiotic susceptibility testing were performed by conventional microbiology.
RESULTS
Peripheral blood smear was positive for Plasmodium falciparum and showed a leukoerythroblastosis with red cell anisopoikilocytosis and left shifted neutrophils. Urine culture confirmed the presence of a multi-resistant E. cloacae. Treatment of underlying conditions resolved the leukoerythroblastic reaction.
CONCLUSIONS
Leukoerythroblastosis may be related to different infectious diseases and may also appear in the context of severe malaria. Bacterial superinfection needs to be investigated.
Topics: Anemia, Myelophthisic; Antimalarials; Blood Transfusion; Child, Preschool; Ciprofloxacin; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Gram-Negative Bacterial Infections; Humans; Malaria, Falciparum; Plasmodium falciparum; Treatment Outcome; Urinary Tract Infections
PubMed: 29272534
DOI: 10.1093/tropej/fmx101 -
Cureus Oct 2017Congenital dyserythropoietic anaemias (CDAs) are very rare, heterogeneous hereditary red blood cell disorders characterized by ineffective erythropoiesis, erythroblast...
Congenital dyserythropoietic anaemias (CDAs) are very rare, heterogeneous hereditary red blood cell disorders characterized by ineffective erythropoiesis, erythroblast morphological abnormalities, haemolysis, and hypoglycosylation of red-blood-cell membrane proteins and lipids. There are four types (I-IV) of the disease identified, and all of them are associated with abnormal maturation and division of erythroid precursors. We report the management of a rare case of CDA type II diagnosed in a 26-year-old pregnant woman.
PubMed: 29308339
DOI: 10.7759/cureus.1811 -
Annales de Biologie Clinique Feb 2020Hemoglobin D-Punjab is a common hemoglobin variant in India but very rare in Morocco. Often, its presence has minimal or no clinical impact. Its heterozygous association...
UNLABELLED
Hemoglobin D-Punjab is a common hemoglobin variant in India but very rare in Morocco. Often, its presence has minimal or no clinical impact. Its heterozygous association with β-thalassemia is exceptional. The purpose of the study is to describe the epidemiological, diagnostic and prophylactic aspects of hemoglobinosis D-Punjab from a family case study.
MATERIAL AND METHODS
Case study of hemoglobinosis D-Punjab in a Moroccan family, diagnosed at the Laboratory of Biochemistry-Toxicology of the Mohammed V Military Teaching Hospital. The biological study was based on iron and hemolysis checkups, hemogram and study of hemoglobin (electrophoresis in alkaline and acid medium, high performance liquid chromatography). The index patient also benefited from sequencing by molecular biology.
RESULTS
The index patient was heterozygous D-Punjab/β-thalassemia, confirmed by molecular biology. Two of her sisters had the same hemoglobin profile. At electrophoresis, all three had hemoglobin D-Punjab higher than 90%, hemoglobin A less than 1% and hemoglobin A higher than 6%. The results of the three hemograms showed similar abnormalities (pseudo-polycythemia, hypochromia, microcytosis, anisopoikilocytosis). Six other members of the family had a thalassemic trait and another three had heterozygous hemoglobinosis D-Punjab.
CONCLUSION
Hemoglobin D-Punjab remains extremely rare in Morocco and very poorly documented in the literature. The number of reported cases is expected to raise due to increasing migration. Biologist advisory services require a precise diagnosis in order to give correct genetic counseling.
Topics: Adolescent; Adult; Child; Family; Female; Genetic Association Studies; Hemoglobins, Abnormal; Humans; Male; Middle Aged; Morocco; Pedigree; beta-Thalassemia
PubMed: 32108581
DOI: 10.1684/abc.2020.1523 -
BMC Pediatrics Jan 2024The administration of high-dose intravenous immunoglobulin (IVIG) is a standard treatment for the management of Kawasaki disease (KD). IVIG is known to be a highly...
BACKGROUND
The administration of high-dose intravenous immunoglobulin (IVIG) is a standard treatment for the management of Kawasaki disease (KD). IVIG is known to be a highly effective and safe treatment.
CASE PRESENTATION
We report the development of hemolytic anemia in seven children receiving repeated doses of IVIG. The children were aged 3-44 months and included 4 girls and 3 boys. All children received 10% IVIG and a second course of immunoglobulin because they did not respond to the first course of immunoglobulin. Two received high-dose aspirin (50 mg/kg), and five received low-dose aspirin (5 mg/kg). Two patients required additional methylprednisolone pulse therapy (30 mg/kg) after the second dose of immunoglobulin, and three patients received oral prednisolone therapy for defervescence. Three patients showed coronary artery dilation during hospitalization and normalized within two months. Pretreatment hemoglobin averaged 11.3-14.2 g/dL, and post-hemolytic anemia hemoglobin ranged from 7.4 to 9.6 g/dL, with a difference of 1.7-6.8 g/dL. Reticulocytes were increased to 3.3-13.2%. Peripheral blood smears showed normochromic normocytic anemia, and anisopoikilocytosis. All children were positive for warm-type antibodies with IgG+, C3d- in direct antiglobulin test, and the blood group was A + in five and B + in two. None of the patients received immunomodulatory therapy or red blood cell transfusions. They were followed for a year and all recovered.
CONCLUSION
Especially, in non-O blood group KD patients who are refractory to initial IVIG and require a second dose of IVIG or 10% formulation the possibility of immune hemolytic anemia should be carefully considered, and close follow-up should be maintained after therapy.
Topics: Child; Female; Humans; Male; Anemia, Hemolytic; Aspirin; Hemoglobins; Immunoglobulins, Intravenous; Mucocutaneous Lymph Node Syndrome; ABO Blood-Group System
PubMed: 38245705
DOI: 10.1186/s12887-024-04546-z -
Cureus Apr 2024Congenital dyserythropoietic anemias (CDAs) are rare hereditary disorders, of which type II CDA is the most common. Mutations in the gene located on chromosome 20...
Congenital dyserythropoietic anemias (CDAs) are rare hereditary disorders, of which type II CDA is the most common. Mutations in the gene located on chromosome 20 result in this autosomal recessive disorder. In this case report, we present a case of CDA II with unique biopsy findings being detected via genetic testing. A female aged 30 years presented with major complaints of pallor weakness and easy fatiguability since childhood. The patient gave a history of 25 units of blood transfusion, the majority of which were transfused during pregnancy, followed by regular transfusions thereafter. On examination, all her vitals were in the normal range. Pallor, frontal bossing, and malocclusion of teeth were noted. Her laboratory workup showed the following: hemoglobin (Hb): 3.7 g/dl; mean corpuscular volume: 83 fl; mean corpuscular Hb: 29 g/dl; mean corpuscular Hb concentration: 34.9 g/dl; red cell distribution width: 30.4%; reticulocyte count (RC): 6.2%; corrected RC: 1.3%; lactate dehydrogenase: 441 IU/L; direct Coombs test/indirect Coombs test: negative; serum iron: 242 microgram/dl; transferrin saturation: 96.08%; ferritin: 1,880 ng/ml; and normal high-performance liquid chromatography and eosin-5'-maleimide binding test. The peripheral blood film showed normocytic normochromic anemia with anisopoikilocytosis in the form of a few spherocytes. No immature cells were seen. After obtaining the patient's consent, we performed a hereditary hemolytic anemia gene analysis test, which showed homozygous missense variation in exon 12 of the gene. The bone marrow examination showed hyperplasia in the erythroid series with dyserythropoiesis, and surprisingly, myelofibrosis grade I-II (WHO 2017) was also observed on biopsy. Patients with CDA type II generally present with variable degrees of anemia along with pallor, icterus, splenomegaly, gallstones, and iron overload. In our case, the diagnosis of CDA type II was made at an adult age. Also, evidence of myelofibrosis was noted in our case, making it worth reporting. The use of a hereditary hemolytic anemia gene analysis panel test came as a rescue for its exact diagnosis. This case report emphasizes the role of molecular genetic testing for early and accurate diagnosis, which, in turn, could help in appropriate treatment planning and proper genetic counseling. The prevalence of CDA type II is still vaguely known; hence, extensive workup of persistent anemias and proper follow-up would be beneficial.
PubMed: 38765414
DOI: 10.7759/cureus.58515 -
Journal of Clinical Pathology Nov 1967Nineteen patients with morphological abnormalities of the red blood cells are described, and these formed approximately 3% of the total cases of cardiac valvular...
Nineteen patients with morphological abnormalities of the red blood cells are described, and these formed approximately 3% of the total cases of cardiac valvular disease. In two patients the abnormal blood film developed after the insertion of an aortic and mitral valve prosthesis respectively, but in another two patients the abnormal blood film was corrected by aortic valve surgery. Anisopoikilocytosis may have been associated with microangiopathic haemolytic anaemia in one patient, but in the others the cardiac valvular disease was severe and other mechanical factors were not present. The mitral valve was involved in 16 patients and the aortic valve in eight. Elliptocytosis was the only abnormality in 11 blood films, schistocytes and burr cells were present in seven, and in three there were a few microspherocytes. Family studies in seven patients produced evidence of hereditary elliptocytosis in three. Anaemia was present in only two patients. One of these had infective endocarditis, and the other developed overt haemolytic anaemia following the replacement of a diseased mitral valve by a Starr-Edwards prosthesis. In this latter case there was a transiently positive direct antiglobulin test, and the anaemia and abnormal blood picture were corrected without further surgical treatment. Haemolytic anaemia did not develop in 23 patients after the insertion of an aortic valve prosthesis or homograft. Indirect evidence of haemolysis was obtained in some patients who were not anaemic. There was a reticulocytosis in one third and serum haptoglobins were decreased or absent in over half of the patients tested.
Topics: Adult; Aged; Anemia, Hemolytic; Blood Cell Count; Coombs Test; Elliptocytosis, Hereditary; Endocarditis, Bacterial; Erythrocytes, Abnormal; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemolysis; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Reticulocytes
PubMed: 5614071
DOI: 10.1136/jcp.20.6.848