1/6. trisomy 21 as the sole abnormality in a refractory anemia with ring sideroblasts.Numerous chromosome abnormalities have been described in myelodysplastic syndromes, but single karyotypic aberrations are much less frequent. We report the case of a 65-year-old woman who presented a trisomy 21 as the sole karyotypic anomaly for a refractory anemia with ring sideroblasts. The nature of such an anomaly is discussed in regard to pathogenesis and prognosis.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
2/6. Acquired haemoglobin H disease in a case of myelodysplastic syndrome.A case of acquired haemoglobin H (HbH) disease with underlying myelodysplastic syndrome in the form of acquired idiopathic sideroblastic anaemia is reported. family studies and subsequent drop in HbH percentage strongly supported the acquired nature of the defect.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
3/6. Autosomal inheritance of sideroblastic anaemia.Inherited sideroblastic anaemia is usually transmitted as an X-linked disorder (Losowsky & Hall 1965). We report a patient in whom family studies indicated autosomal inheritance, with direct transmission from father to son. The severe nature of the sideroblastic abnormality in the proband may be due to interaction between the sideroblastic trait and a single allele for idiopathic haemochromatosis.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
4/6. Energy dispersive x-ray microanalysis of mitochondrial deposits in sideroblastic anemia.Energy dispersive x-ray microanalysis was used to analyze mitochondrial and lysosomal iron-containing deposits in sideroblastic anemia. Although it has been previously known that these deposits contain iron by inference from Prussian blue staining, the possible presence of other cations as well as the nature of the anions present has not been identified. The results show that the mitochondrial deposits in erythroid cells have peaks for iron and phosphorus indicating that they do not represent calcifications which commonly occur following injury and that the principal anion may be phosphorus. Studies of hemosiderin and ferritin aggregates in lysosomes of macrophages in the same bone marrow samples again reveal similar peaks for iron and phosphorus. The results also indicate the probable similarity of mitochondrial and macrophage deposists although ferritin itself was never identified in the mitochondrial deposits. The results illustrate the potential of this method for diagnostic and investigative pathology.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
5/6. Myelodysplasia in a patient with pre-existing paroxysmal nocturnal haemoglobinuria: a clonal disease originating from within a clonal disease.Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic anaemia, clonal in nature, due to somatic mutation. PNH may evolve to aplastic anaemia; more rarely to a myelodysplastic syndrome (MDS) or to acute myeloid leukaemia (AML). We have studied a patient who suffered from PNH and later developed refractory anaemia with ringed sideroblasts (RARS) associated with trisomy 8. By testing peripheral blood cells with appropriate antibodies we have shown that all of the red cells, neutrophils and monocytes, as well as 20% of the lymphocytes, belonged to the PNH clone; in contrast, only 43% of neutrophils and 22% of monocytes belonged to the MDS clone. We infer that the MDS must have arisen from within the PNS clone.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
6/6. X-linked sideroblastic anemia: identification of the mutation in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) in the original family described by Cooley.In 1945, Thomas Cooley described the first cases of X-linked sideroblastic anemia (XLSA) in two brothers from a large family in which the inheritance of the disease was documented through six generations. Almost 40 years later the enzymatic defect in XLSA was identified as the deficient activity of the erythroid-specific form of delta-aminolevulinate synthase (ALAS2), the first enzyme in the heme biosynthetic pathway. To determine the nature of the mutation in the ALAS2 gene causing XLSA in Cooley's original family, genomic DNAs were isolated from two affected hemizygotes, and each ALAS2 exon was PCR amplified and sequenced. A single transversion (A to C) was identified in exon 5. The mutation predicted the substitution of leucine for phenylalanine at residue 165 (F165L) in the first highly conserved domain of the ALAS2 catalytic core shared by all species. No other nucleotide changes were found by sequencing each of the 11 exons, including intron/exon boundaries, 1 kb of 5'-flanking and 350 nucleotides of 3'-flanking sequence. The mutation introduced an Mse I site and restriction analysis of PCR-amplified genomic dna confirmed the presence of the lesion in the two affected brothers and in three obligate heterozygotes from three generations of this family. Carrier diagnosis of additional family members identified the mutation in one of the proband's sisters. After prokaryotic expression and affinity purification of both mutant and normal ALAS2 fusion proteins, the specific activity of the F165L mutant enzyme was about 26% of normal. The cofactor, pyridoxal 5'-phosphate, activated and/or stabilized the purified mutant recombinant enzyme in vitro, consistent with the pyridoxine-responsive anemia in affected hemizygotes from this family.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |