Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in the RAB27A gene. It is characterized by cutaneous hypopigmentation, immunodeficiency, and hemophagocytic lymphohistiocytosis. We describe 2 brothers who had GS2 with clinically diverse manifestations. The elder brother presented with a purely neurological picture, whereas the younger one presented with fever, pancytopenia, hepatosplenomegaly, and erythema nodosum. Considering that cutaneous hypopigmentation was a common feature between the brothers, genetic analysis for Griscelli syndrome was performed. As the elder sibling had died, mutation analysis was only performed on the younger sibling, which revealed a novel homozygous mutation in the RAB27A gene on chromosome 15 showing a single-base substitution (c.136T>A p.F46I). Both parents were heterozygous for the same mutation. This confirmed the diagnosis of GS2 in the accelerated phase in both siblings. The atypical features of GS2 in these cases are a novel mutation, isolated neurological involvement in one sibling, association with erythema nodosum, and 2 distinct clinical presentations in siblings with the same genetic mutation.
Chromosomes, Human, Pair 15 ; Diagnosis ; Erythema Nodosum ; Fever ; Humans ; Hypopigmentation ; Lymphohistiocytosis, Hemophagocytic ; Nervous System Diseases ; Pancytopenia ; Parents ; Siblings*

BACKGROUND: Some reports have shown that co-inheritance of alpha-thalassemia and sickle cell disease improves hematological parameters and results in a relatively mild clinical picture for patients; however, the exact molecular basis and clinical significance of the interaction between alpha-thalassemia and sickle cell disease in India has not yet been described. There is little agreement on the clinical effects of alpha-thalassemia on the phenotype of sickle cell disease. METHODS: Complete blood count and red cell indices were measured by an automated cell analyzer. Quantitative assessment of hemoglobin variants HbF, HbA, HbA2, and HbS was performed by high performance liquid chromatography (HPLC). DNA extraction was performed using the phenol-chloroform method, and molecular study for common alpha-deletions was done by gap-PCR. RESULTS: Out of 60 sickle cell anemia patients, the alpha-thalassemia genotype was found in 18 patients. Three patients had the triplicated alpha-genotype (Anti alpha-3.7 kb), and the remaining patients did not have alpha-deletions. This study indicates that patients with co-existing alpha-thalassemia and sickle cell disease had a mild phenotype, significantly improved hematological parameters, and fewer blood transfusions than the patients with sickle cell anemia without co-existing alpha-deletions. CONCLUSION: Co-existence of alpha-thalassemia and sickle cell anemia has significant effects on the phenotype of Indian sickle cell patients.
alpha-Thalassemia ; Anemia, Sickle Cell ; Blood Cell Count ; Blood Transfusion ; Chromatography, Liquid ; DNA ; Erythrocyte Indices ; Genotype ; Hemoglobinopathies ; Hemoglobins ; Humans ; India ; Phenotype

BACKGROUND: Aberrant myeloid antigen (MA) co-expression and high expression of CD34 antigen on the blasts of acute lymphoblastic leukemia (ALL) patients are independently reported to have a role in pathogenesis and prognosis. This study was conducted to determine whether these two parameters are related. METHODS: A total of 204 cases of ALL were included in an analysis of blast immunophenotypic data. CD34 expression was categorized as low when less than 50% of blasts were CD34-positive (CD34low) and as high when 50% or more were CD34-positive (CD34high). RESULTS: Of 204 cases of ALL, 163 and 41 were of B-cell origin (B-ALL) and T-cell origin (T-ALL), respectively. Of all cases, 132 (64.7%) showed co-expression of MA and among these, 101 (76.51%) were CD34high, while the remaining 31 (23.48%) were CD34low. Of 72 cases without MA co-expression, 25 (34.72%) were CD34high and 47 (67.25%) were CD34low. Furthermore, of 163 cases of B-ALL, 111 showed co-expression of MA and 84 of these were CD34high. Of 52 cases of B-ALL without MA expression, 22 were CD34high. Among 41 cases of T-ALL, 21 co-expressed MA, 17 of which were CD34high. Moreover, all 20 cases of T-ALL without co-expression of MA were CD34low. These differences were statistically significant. CONCLUSION: We observed a strong correlation between aberrant MA expression and CD34high expression on the blasts of ALL. We hypothesize that these different patient subsets may represent unique prognostic characteristics.
Antigens, CD34 ; B-Lymphocytes ; Flow Cytometry ; Humans ; Immunophenotyping ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; T-Lymphocytes ; Tertiary Care Centers*