Gurjeewan Garewal

Acute Febrile Neutrophilic Dermatosis (Sweet's Syndrome) in Myelodysplastic Syndrome

This is the first report of the rare association of acute febrile neutrophilic dermatosis (Sweets syndrome) and myelodysplastic syndrome (MDS) in a child. The skin lesions showed a dramatic response to colchicine.

Prevalence of the H63D mutation of the HFE in north India: its presence does not cause iron overload in beta thalassemia trait

Abstract:  Objectives: To determine the allele frequency in the north Indian population of the two mutations in the HFE gene, the C282Y and H63D, which are responsible for causing hereditary haemochromatosis particularly in Caucasians of north European descent. We also wanted to correlate these mutations with the iron status in beta thalassemia traits. Patients and Methods: Sixty normal subjects and 215 individuals with beta thalassemia trait from north India were screened for the C282Y and H63D by polymerase chain reaction‐restriction fragment‐length polymorphism (PCR‐RFLP). We studied the iron status in these subjects and correlated the same with the HFE gene mutations. Results: On screening for the C282Y gene mutation, all individuals were detected to be of the wild‐type. The overall allele frequency of H63D was 9.09% with three individuals being homozygous for 63D. No statistically significant difference in the iron status was detected between the individuals of the wild‐type and mutant for H63D. Haplotyping of the homozygous 63D alleles revealed the pattern to be identical to the Europeans. Conclusions: Our study shows that H63D is prevalent and C282Y is rare in north Indians and the presence of 63D mutation does not increase body iron as measured by serum ferritin in beta thalassemia traits. Haplotype of H63D gene mutation is of an European haplotype, indicating a common origin.

Serum transferrin receptor-ferritin index shows concomitant iron deficiency anemia and anemia of chronic disease is common in patients with rheumatoid arthritis in north India

Anemia is a frequent cause of morbidity in patients with rheumatoid arthritis (RA). We studied the prevalence of anemia of chronic disorders (ACD) and ACD with coexistent iron deficiency anemia (IDA) in patients with RA using sTfR/log ferritin ratio (sTfR - F index). Complete blood counts, percent transferrin saturation, serum ferritin, sTfR, sTfR-F index measurements were carried out in 100 anemic RA patients. Twenty-five IDA subjects without any other illness and 25 age- and sex-matched normal controls were studied. Prevalence of anemia in RA patients was 50.5%. Patients with sTfR-F index value < 1.5 were classified as pure ACD and patients with sTfR-F index value> 1.5 were classified as ACD with coexistent IDA. Using these criteria, 20% patients were found to have pure ACD and 80% patients had coexistent ACD and IDA. In the normal control group, sTfR-F index was found to be 0.16-1.8. We found that sTfR-F index can clearly distinguish IDA control cases and normal subjects with no overlap in the range of sTfR-F index.

HEMATOLOGICAL DISORDERS IN DOWN SYNDROME: Ten-Year Experience at a Tertiary Care Centre in North India

A total of 239 cases of Down syndrome (DS) were seen in the genetic clinic between 1992 and 2003, of which of 15 had hematological manifestations at presentation. These comprised 4 cases of transient myeloproliferative disorder (TMD), 3 cases of TMD/acute leukemia, 4 cases of acute leukemia (AL), 2 of dual deficiency anemia, and 1 case each of myelofibrosis and idiopathic thrombocytopenia. This study emphasizes the fact that an abnormal hemogram in a DS patient does not necessarily indicate AL/TMD, as a considerable number of the cases in this study had other hematological abnormalities. TMD can be differentiated from acute leukemia only on follow-up.

Spectrum of β-Thalassemia Mutations in Punjabis

Abstract In the present paper the prevalence of the β -thalassemia has been reported. It has been assaved that the trust is 3.5% and nearly half of these individuals belong to the Khatri-Arora castes. These families have migrated from the South-west districts of the undivided Punjab, now in Pakistan. In thalassemia major families, the common five mutations account for 93.5% of the alleles with another 3.35 % with CAP+1 and–88 (C-T), facilitating the prenatal diagnosis of thalassemia in this population.

Derangement of DNA Synthesis in Erythroleukaemia. Normal Deoxyuridine Suppression and Impaired Thymidine Incorporation in Bone Marrow Culture

Deoxyuridine (dU) suppression test (i.e. ability of exogenous dU to suppress the incorporation of subsequently added 3H-thymidine into DNA) and the incorporation of 3H-thymidine (3H-TdR) alone without dU were studied in bone marrow cultures from 10 patients with erythroleukaemia, 10 patients with vitamin B12/folate-deficient megaloblastic anaemia and 10 haematologically normal subjects. Despite morphological resemblance between megaloblastosis in erythroleukaemia and nutritional megaloblastosis, the dU suppression values in erythroleukaemia were within normal range in contrast to abnormal dU suppression in vitamin B12/folate-deficient megaloblastic bone marrows. The incorporation of 3H-thymidine alone was significantly lower in erythroleukaemia than in normal or vitamin B12/folate-deficient megaloblastic bone marrows. Autoradiographic studies showed that 3H-TdR labelling indices as well as mean grain count (MGC) of basophilic and polychromatic erythroblasts were significantly lower in erythroleukaemia than in normal or vitamin B12/folate-deficient bone marrows. The reduced incorporation of 3H-TdR in erythroleukaemia erythroblasts was probably not due to deficiency of the salvage pathway enzyme, thymidine kinase, since MTX (10(-5) M) which blocks the de novo pathway of thymine-DNA synthesis, enhanced the incorporation of 3H-TdR into erythroblasts in erythroleukaemia as well as in normal bone marrows. A high intracellular pool of thymidine-triphosphate (dTTP) due to defective DNA synthesis may allosterically inhibit thymidine kinase and 3H-TdR incorporation.

The clinical significance of the spectrum of interactions of CAP+1 (A→C), a silent β‐globin gene mutation, with other β‐thalassemia mutations and globin gene modifiers in north Indians

Objectives: To assess the clinical significance of the interactions of CAP+1 (A→C), a silent β‐globin gene mutation, with other β‐thalassemia mutations and globin gene modifiers in north Indians. Methods: The clinical phenotypes associated with compound heterozygosity for the CAP+1 (A→C) mutation with other β‐thalassemia mutations, together with the potential effect of the genetic modifiers α‐thalassemia and the Xmn‐1Gγ C→T polymorphism were studied in 30 patients. The frequency of the CAP+1 (A→C) polymorphism was determined and an analysis of the red cell indices, HbA2 levels, iron status, and α‐globin genes was carried out in 35 heterozygotes. Results: Based on an analysis of 1075 β‐thalassemia alleles the CAP+1 (A→C) mutation constituted 3.2% of north Indians. There was a wide spectrum of phenotypic severity in compound heterozygotes; 18 of 30 were transfusion dependent. There was a very high frequency of the −/− genotype of the Xmn‐1Gγ polymorphism in compound heterozygotes. Analysis of 35 heterozygotes indicated that approximately half were hematologically normal and therefore genuine ‘silent’ carriers. Conclusions: Compound heterozygotes for CAP+1 (A→C) and other severe β‐thalassemia alleles are phenotypically severe enough to necessitate appropriate therapy and counseling. The unexpected severity of these interactions may be due, in part, to the high frequency of β‐thalassemia alleles associated with the Xmn‐1Gγ− allele in Indian populations. It is concluded that the CAP+1 (A→C) mutation can pose serious difficulties in screening and counseling programs in populations in which it occurs at a significant frequency.

Accelerated phase at initial presentation: An uncommon occurrence in Chédiak-Higashi syndrome

The authors describe an Indian child, who presented in the accelerated phase of the Chédiak-Higashi syndrome. The disease usually presents in early childhood with recurrent skin and mucosal infections. This patient had subtle pigmentary abnormalities and no family history of the disease, which made the clinical diagnosis difficult. The cytopenias, hepatosplenomegaly, lymphohistiocytic infiltrate in the bone marrow, and the characteristic granules in the leucocytes clinched the diagnosis. This case underscores the importance of a bone marrow examination in patients with unusual presentations of rare disorders.

AUTOMATED RETICULOCYTE RESPONSE IS A GOOD PREDICTOR OF BONE-MARROW RECOVERY IN PEDIATRIC MALIGNANCIES

The authors attempted to establish the benefits of flow cytometry-based reticulocyte analysis over absolute neutrophil count (ANC) recovery. Serial hemograms of 18 pediatric cases of hematologic malignancies were analyzed until day 35 of chemotherapy. Immature reticulocyte fraction (IRF) showed early recovery in 44.4% of cases compared to ANC. Since reticulocyte fractions are not influenced by infections, they are a better parameter of bone marrow regeneration than ANC. The study shows that IRF can act as a harbinger of regenerating bone marrow activity in patients with persistent neutropenia and guide the modulation of antibiotic strategies in these patients.

Serum Iron Levels and Hepatic Iron Overload in Patients with Nonalcoholic Steatohepatitis

To the Editor: We read with interest the article by Uraz et al. [1] on the serum iron levels and hepatic iron overload in patients with nonalcoholic hepatitis (NASH) and chronic hepatitis. They studied 25 patients, each with biopsy-proven NASH and chronic viral hepatitis, and found higher serum iron and ferritin levels in patients with chronic viral hepatitis in comparison to those with NASH. Five (20%) patients with chronic viral hepatitis showed positivity for iron on Perls’ Prussian blue staining on liver biopsy compared to none in patients with NASH. We agree with Uraz et al. [1] that patients with nonalcoholic fatty liver disease (NAFLD) do not show evidence of iron overload [2]. We studied iron parameters in 59 patients with NAFLD (38 biopsy proven) (Table 1). Only two (3%) patients had high serum iron (>150 μg/dl), five (8%) had high transferrin saturation (>55%), and four (7%) had high serum ferritin (>250 ng/dl). In contrast to Uraz et al. [1], even though the Perls’ Prussian blue staining for iron on liver biopsy was positive in 10 of 30 (33%) patients in whom this information was available