Distal arthrogryposis syndrome.

A 5-month-old male infant presented with weak cry, decreased body movements, tightness of whole body since birth, and one episode of generalized seizure on day 4 of life. He was born at term by elective caesarian section performed for breech presentation. The child had failure to thrive, contractures at elbow and knee joints, hypertonia, microcephaly, small mouth, retrognathia, and camptodactyly. There was global developmental delay. Abdominal examination revealed umbilical and bilateral inguinal hernia. Visual evoked response and brainstem evoked response audiometry were abnormal. Nerve conduction velocity was normal. Magnetic resonance imaging of brain revealed paucity of white matter in bilateral cerebral hemispheres with cerebellar and brain stem atrophy. The differential diagnoses considered in the index patient were distal arthrogryposis (DA) syndrome, cerebroculofacioskeletal syndrome, and Pena Shokier syndrome. The index patient most likely represents a variant of DA: Sheldon Hall syndrome.

Hairy cell leukemia: Clinical, pathological and ultrastructural findings in Asian-Indians.

Background: Hairy-cell leukemia (HCL), lymphoproliferative disease of older age, is characterized by projections from surface of abnormal cells. Aim: The aim was to study the clinical presentation and ultrastructural changes in hairy cells (HCs) following cladribine treatment. Settings and Design: Clinical presentation, peripheral smear, bone marrow aspiration and biopsy of HCL cases diagnosed over a period of three years were reviewed. Materials and Methods: Consecutive HCL cases in Hematology clinic of a tertiary care center were enrolled. Tartarate-resistant acid phosphatase (TRAP) test was done to detect HCs and electron microscopy was done to demonstrate initial ultrastructural changes and alterations following cladribine therapy. Results: Fifteen cases of HCL, aged 32-57 years (median 47 years) were studied. The clinical presentation included splenomegaly in 15 (100%), fever in 10 (67%), hepatomegaly and pain abdomen in eight (53%), fatigue in nine (60 %) cases. The commonest laboratory features were monocytopenia in 13 (87%), neutropenia in 12 (80%), anemia in 10 (67 %) and pancytopenia in nine (60%). All patients showed symptomatic improvement on cladribine therapy. Electron microscopy after treatment (three months) showed loss of the finger like projections, characteristic bald lymphocytes, loss of ribosomal lamellar complexes, as well as decrease in mitochondria and vacuoles. Conclusions: Indian patients with HCL are younger. Cladribine is an effective therapy for these patients and leads to complete response in most of the patients. There is a significant improvement in the ultrastructural features following cladribine therapy.

Evidence for non-HFE linked hemochromatosis in Asian Indians.

BACKGROUND: Hereditary hemochromatosis is commonly due to two HFE1 (Histone Family E1) gene mutations - H63D and C282Y. Mutations in the Asian Indians are less well studied. AIMS: The aim of this preliminary study was to find out the prevalence of HFE gene mutations in nonviral liver cirrhosis patients. SETTINGS AND DESIGN: Unexplained liver cirrhosis cases with transferrin saturation> 45%, attending the gastroenterology clinic in the years 2004 and 2005 were subjects of the prospective study. Asymptomatic individuals with negative family history of hemolytic anemia or liver disease served as controls. MATERIALS AND METHODS: The clinical presentation was recorded in the patients. Transferrin saturation was estimated by standard colorimetric technique. The two common mutations in HFE1 gene and Y250X mutation of TFR (transferrin receptor) gene were studied by polymerase chain reaction based methods. RESULTS: A majority of the cases were sporadic, but family history was positive in four patients. In one family with multiple affected members, there was clear evidence of autosomal dominant inheritance. Seven out of 31 (22.6%) of unexplained cirrhosis cases were positive for mutations. One was homozygous for H63D. In healthy controls, prevalence was 8.1% (6/74). None of the patients or controls was positive for C282Y mutation of HFE1 or Y250X of TFR gene. CONCLUSIONS: Thus, in a number of cases of hemochromatosis in Indians, a gene with dominant inheritance may be involved in causation of the phenotype. The prevalence of HFE mutations in Indians is comparable to that reported from neighboring countries. It is worth studying other mutations in HFE gene and other iron overload genes in cryptogenic cirrhosis cases.

Cord blood analysis for prenatal diagnosis of thalassemia major and hemophilia A.

Beta thalassemia and Hemophilia A are common genetic disorders for which prenatal diagnosis (PND) is an accepted option. Our aim was to evaluate cord blood analysis as a method for PND of these disorders. Cord blood samples at 18-26 weeks gestation from nine mothers with previous thalassemia major child and five families with previous hemophilia A were studied. In the former; HbF, HbA2 and HbF were determined by high performance liquid chromatography (HPLC) and in latter; Factor VIII and IX assays were done by one stage method. In HPLC studies for thalassemia, three out of nine fetuses were affected, five were carriers and one was normal. In hemophilia PND samples, 2 out of five fetuses were affected. Thus, HPLC and factor VIII assay in cord blood are feasible alternatives for PND in Beta thalassemia and hemophilia A respectively, especially when DNA analysis is uninformative or there are financial constraints.

Hemoglobin E-beta thalassemia: factors affecting phenotype.

The phenotype of E-beta-thalassemia is affected by several genetic factors. The aim of this study was to analyze severity of E-beta-thalassemia and correlate with HbE, HbF, E/F ratios, beta-mutation and Xmn I polymorphism. Thirty cases of E-beta-thalassemia (23 with childhood onset) were studied. HbE levels were quantitated by HPLC. Xmn1 polymorphism and beta-mutations were studied by PCR-RFLP and ARMS respectively. Commonest features were pallor (100%), splenomegaly (74%), and hepatomegaly (65%), 43% (10/23) were on regular transfusions at diagnosis. One case presented with paraplegia. Patients heterozygous for Xmn I polymorphism (+/-) had later onset (>3 yrs) compared to homozygous (-/-) absence (0.5-2.8 yrs). Most (69.6%) showed beta-mutation IVS 1-5 (G-->C). Negative correlation was found between age of onset and HbE. Thus, presentation is similar to previously reported Thai cases. Heterozygosity of Xmn I polymorphism also delays disease onset. Early diagnosis facilitates appropriate management and prenatal diagnosis.

Internet resources for hemato-oncologist.

AIM OF THE STUDY: To find out sites of interest for the hemato-oncologist on the internet. METHODOLOGY: Use of search engines like www.google.com and www.yahoo.com and selective identification of the relevant sites by thorough browsing. RESULTS: There are several sites which can be useful to the hemato-oncologist. Some of the sites are related to hematology, hemato-oncology, hemato-pathology, etc. were as some are disease specific e.g., thalassemia, hemophilia, myelodysplastic syndrome. Reliability of the sites have to be judged carefully. CONCLUSIONS: Certain sites provide specific information for selected diseases, and accordingly online browsing is required. Latest articles can be retrieved from Pubmed, Biomednet (www.bmn.com) and few general haematology sites like www.medweb.emory.edu and the cancer-related site www.aacr.org. The benefits of internet include rapid access to relevant information, easy use and also e-consultations.

Clinical profile of hereditary spherocytosis in North India.

AIMS OF THE STUDY: Hereditary spherocytosis (HS) is a familial hemolytic disorder manifesting as anaemia, recurrent jaundice, splenomegaly with marked heterogeneity in clinical presentation. The objective was to study the clinical spectrum of the disorder in India. METHODOLOGY: We studied 50 HS patients and followed them for up to six years (Age range 2-47 years). RESULTS: The presenting features were jaundice 35 out of 50, anaemia 30 out of 50 (requiring blood transfusion in 25). Splenomegaly was found in all patients. Increased osmotic fragility was found in all patients whereas spherocytes were found in only 19 out of 42 patients. Reduced red cell survival was noted in 9/12 patients studied with 51Cr labeled RBCs. There was a definite improvement in the hemoglobin values in those who underwent splenectomy. Thirteen cases had similarly affected family member/s. Fifteen of the cases had family history consistent with autosomal dominant (AD) inheritance (eight families) while in six cases (5 families), inheritance was likely to be autosomal recessive (AR). There was intrafamilial variability in the age of presentation in the AD families. CONCLUSIONS: Our results suggest that both autosomal dominant and recessive patterns of HS are seen in India and the clinical profile of the Indian HS patients is similar to that described in other populations. HS presenting in childhood is also not uncommon. However, the predominant underlying protein defect in Indian patients needs to be characterized.

Utility of databases and information technology in pediatric neurology.

Significant number of neurological patients in the pediatric age group have genetic and/or metabolic basis. It is difficult to remember details of each of them as their number is very large and the disorders are encountered infrequently. This impracticality necessitates the use of various websites and data base search. The internet has become a tool by which one can obtain and disseminate information. It has enhanced the medical person's ability to know at the earliest the developments in different medical specialities. Furthermore, these rare disorders are being recognized on the basis of specialized tests available only at selected centres which deal with few of these disorders. Our objective is to provide pediatric neurologists easy access to the expanding body of medical information and also to make them aware of the advancements in information technology, which is likely to facilitate telemedicine as a future consultancy service. Information about these diseases can also be facilitated by e-consultations.

Clinical and molecular diagnosis of spinal muscular atrophy.

The spinal muscular atrophies are a group of disorders characterized by flaccid limb weakness. It is necessary to differentiate these from other causes and identify the SMA variants. In classical SMA, majority of the patients shows homozygous deletion of the telomeric SMN gene (SMN1) on chromosome 5q. The availability of DNA analysis has allowed proper genetic counseling and prenatal diagnosis in the affected families. Application of newer techniques has enabled more accurate carrier detection. Our objective is to stress the variability in the clinical features and recent advances in the molecular diagnosis for SMA.