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The article focuses on the first reported case of GATA1-related X-linked thrombocytopenia with co-inherited β-thalassemia trait (XLTT) in a 16-year-old boy. Topics include the role of GATA1 mutations in various hematopoietic disorders, the specific mutation (p.Arg216Gln) affecting GATA1 in this case, and the complexity of the phenotype resulting from the co-inheritance of XLTT and β-thalassemia.

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(anti3.7)/ααα(anti4.2) and deletional α‐thalassemia testing by multiplex gap‐PCRs, and Xmn1Gγ 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 αααanti3.7, while 3 (6.4%) had αααanti4.2 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 β0 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 + ααα4.2 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. [ABSTRACT FROM AUTHOR]

Hyperunstable hemoglobins (Hbs) are challenging to diagnose and may be missed on conventional hemolytic anemia work-up. Here, we report the case of a 2-year-old Indian boy with infancy-onset severe hemolytic anemia. Its etiology was revealed by targeted next-generation sequencing (NGS) to be the rare Hb Mizuho (HBB: c.206T>C). This variant had been missed on the initial routine laboratory investigations (heat and isopropanol tests for unstable Hbs) owing to its hyperunstable nature. [ABSTRACT FROM AUTHOR]

Compound heterozygosity for one of the Hb Lepore mutations and β-thalassemia (β-thal) is a rare cause of non transfusion-dependent thalassemia. We report a 4-year-old boy who presented clinically as homozygous/compound heterozygous β-thal intermedia (β-TI), an impression that was corroborated by the initial hemoglobin (Hb) high performance liquid chromatography (HPLC). However, the correct diagnosis of a rare compound heterozygous Hb Lepore-Hollandia/β-thal was revealed after parental studies and molecular analyses including β-globin gene sequencing. Our patient highlights the importance of a logical stepwise multi modality approach and the vital importance of parental screening and molecular studies in accurate characterization of complex hemoglobinopathies. Correct diagnosis is especially crucial if pre natal detection is anticipated for future pregnancies. Molecular analyses alone may not compensate for the unavailability of parental testing. This is because the molecular results may be misinterpreted, especially if limited tests are conducted. The infrequent prior reports of this combination from distant parts of the Indian subcontinent suggests that the origin of Hb Lepore-Hollandia from sporadic mutations occurs in isolated families. [ABSTRACT FROM AUTHOR]

The article presents a study on globin gene structure Hemoglobin (Hb) Q-India, for knowing its hematological and Capillary electrophoresis-High-performance liquid chromatography (CE-HPLC) features. Topics include cases confirmed by alkaline potential of hydrogen (pH) agarose gel electrophoresis, blood counts in HbQ showed lower mean corpuscular volume and mean corpuscular hemoglobin, and increasing cases of Q-India traits with microcytosis among boys in India.

The article discusses the findings of a study which investigated the application of cation-exchange (CE)-high performance liquid chromatography (HPLC) in the quantification of hemoglobins and its variants. Topics covered include the unpredictable discrepancies of cellulose acetate electrophoresis (CAE) densitometric hemoglobin fraction levels and the disadvantages of using quantitative screening technique in clinical practice.

A 60-year-old male with myelodysplastic syndrome with excess blasts-1 had unexplained microcytic hypochromic anemia. The cause of his anemia was revealed on supravital staining, hemoglobin studies and next-generation sequencing to be a novel hemizygous potentially pathogenic missense/splice site variant NM_000489.5:c.6848A>C, (p.Lys2283Thr) in exon 31 of the ATRX gene. [ABSTRACT FROM AUTHOR]

Background High performance liquid chromatography in a newborn girl with congenital cyanosis and a unilateral cleft palate revealed a variant hemoglobin with retention time of 4.8 min, similar to hemoglobin Q-India. Since hemoglobin Q-India did not explain the cyanosis, further investigations were initiated. Methods Sequencing of α-globin genes revealed hemoglobin M-Iwate ([α87 (F8) His→Tyr]) that was confirmed on restriction enzyme analysis. Results Hemoglobin M-Iwate is a rare methemoglobinemic variant formed due to a point mutation in the α-globin gene. Primarily reported from the Iwate prefecture of Japan, there have been occasional case reports from other regions as well. Inherited methemoglobinemia finds only rare mention in Indian literature while hemoglobin M-Iwate has not been reported from India. Conclusions This case illustrates the step-wise logical diagnostic approaches necessary to elucidate the cause of methemoglobinemia in an otherwise healthy child with cyanosis. [ABSTRACT FROM AUTHOR]