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Cases reported "Anemia, Hemolytic, Congenital"
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1/76. Germline mosaicism of MPZ gene in Dejerine-Sottas syndrome (HMSN III) associated with hereditary stomatocytosis.We report on two sisters with Dejerine-Sottas syndrome (DSS) who had a heterozygous Gly 167 Arg mutation in the myelin protein zero (MPZ) gene and hereditary stomatocytosis (HSt). Genetic haplotype analysis suggested that the allele with the MPZ gene mutation originated from maternal lineage. However, the parents, who were normal clinically and electrophysiologically, had no mutation in the MPZ gene. Therefore, the MPZ gene mutation in these sisters was due to germline mosaicism of the MPZ gene in their mother. Stomatocytosis was detected in their mother and a sister who had no neurological symptoms, and therefore autosomal dominant HSt was suspected in this family. As stomatocytosis is very severe in our patients with DDS, we speculate that the association of DSS with stomatocytosis is coincidental but may have additively affected erythrocyte morphology. To our knowledge, these are the first familial cases of DSS with a mutation due to germline mosaicism of the MPZ gene to be reported.- - - - - - - - - - ranking = 1keywords = syndrome, type (Clic here for more details about this article) |
2/76. Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from spain: clinical and molecular studies.In four unrelated patients with chronic haemolysis and markedly reduced red blood cell (RBC) glutathione (49.5%, 12.6%, 11.5% and 15% of the normal concentration respectively), a severe glutathione synthetase (GSH-S, EC 6.3.2.3) deficiency was found. One case exhibited a neonatal haemolytic anaemia associated with oxoprolinuria, but without neurological manifestations. The family study revealed GSH-S activity in both parents to be around half the normal level, a finding consistent with the presumed autosomal recessive mode of inheritance of this enzymopathy. Two cases exhibited a well-compensated haemolytic syndrome without anaemia or splenomegaly at steady state. One of these cases was diagnosed after an episode of acute haemolytic anaemia after fava bean ingestion. The remaining patient suffered from moderate to severe chronic non-spherocytic haemolytic anaemia and splenomegaly, and required occasional blood transfusion for a haemolytic crisis associated with drug ingestion. In this patient, the anaemia was corrected by splenectomy. In addition to GSH-S, a panel of 16 other RBC enzyme activities was also studied in all the patients. hexokinase, aldolase, glucose-6-phosphate dehydrogenase and pyruvate kinase activities all increased; these increases were to be expected, given the rise in the number of circulating reticulocytes. In two patients, the incubation of RBCs with hydrogen peroxide revealed an enhanced production of malonyldialdehyde. dna analysis showed a homozygous state for 656 A-->G mutation in patients 2 and 3. The GSH-S gene of patient 1, studied elsewhere, revealed an 808 T-->C. The GSH-S gene of patient 4 was not available for study. The present study demonstrates that GSH-S deficiency is also present in spain and further supports the molecular and clinical heterogeneity of this enzymopathy- - - - - - - - - - ranking = 0.19425471597003keywords = syndrome (Clic here for more details about this article) |
3/76. Haemoglobin Q-thailand and hereditary spherocytosis in a Chinese family.A Chinese family with concurrent hereditary spherocytosis (HS) and haemoglobin (Hb) Q-thailand is described. The Hb Q-thailand mutation was found on the remaining alpha1 globin gene on a chromosome 16 containing the (-alpha 4.2) deletion. Active haemolysis in members of this family is segregated with the HS phenotype, and the Hb Q-thailand in the heterozygous state does not seem to show any modulating effect on HS.- - - - - - - - - - ranking = 0.028726420149862keywords = type (Clic here for more details about this article) |
4/76. Severe jaundice in a patient with a previously undescribed glucose-6-phosphate dehydrogenase (G6PD) mutation and Gilbert syndrome.A patient with chronic hemolytic anemia and G6PD deficiency was noted to be severely jaundiced and to have a high serum ferritin level. Analysis of his dna revealed only heterozygosity for the c.187 C-->G (H63D) mutation of HFE, but showed that he was homozygous for the UDP glucuronosyltransferase promoter mutation of Gilbert's disease and that he had a previously undescribed mutation of G6PD, c.832 T-->C (Ser278Pro). The new variant was named G6PD La Jolla.- - - - - - - - - - ranking = 0.77701886388011keywords = syndrome (Clic here for more details about this article) |
5/76. Red cell calcium leak in congenital hemolytic anemia with extreme microcytosis.A child with congenital hemolytic anemia, extreme microcytosis and bizarre red cell morphology has been studied. splenectomy at the age of 21 mo greatly improved the hemolytic anemia, although red cell morphology was unchanged. Aniso- and poikilocytosis were marked on a stained smear, and there were many small hyperchromatic cells of irregular shape. The MCV of 25 cu mu was very low and the MCHC was normal. osmotic fragility of fresh blood was increased, and postsplenectomy blood showed a fraction of extremely fragile cells. Concentration and fluxes of Na+ and K+ were normal, except K+ efflux, which was stimulated by external Ca2+. Inward Ca2+ movement into the patient's red cells was elevated three- to fourfold above red cells of the same mean age. Red cell Ca2+ concentration was raised 2.5 times normal and most of the Ca2+ was localized in the stroma. Red cell lipid, sialic acid, and ouabain-binding sites, all per milliliter of cells, were increased by 16%-23%, and, since these substances estimate the amount of membrane, it was likely that Ca2+ content per unit of membrane area was at least twice normal. Deformability of the cells, as judged by their filterability was markedly impaired. It was concluded that the red cell membrane was defective, and an increased membrane Ca2+ content was associated with reduced deformability, hemolysis, and distorted red cell morphology in this syndrome.- - - - - - - - - - ranking = 0.19425471597003keywords = syndrome (Clic here for more details about this article) |
6/76. Sub-lethal hydrops as a manifestation of dehydrated hereditary stomatocytosis in two consecutive pregnancies.Dehydrated hereditary stomatocytosis (DHS) is a rare congenital hemolytic anemia mapping to 16q23-q24. We showed recently that it is part of a pleiotropic syndrome likely to display pseudohyperkalemia and/or different forms of fetal and placental fluid collections. Here, we report a woman with DHS. She had two consecutive pregnancies associated with severe fetal hydrops. Hydrops would probably have been lethal in the absence of appropriate removal of ascites and excess amniotic fluid. In utero exchange transfusion, performed once, was useless, because anemia was not pronounced enough to be the cause of the hydrops. In both newborns, ascites resolved within a week following birth and never recurred. The association of hydrops and hemolytic anemia suggests the possibility of DHS. Symptomatic treatment of the hydrops assists survival until spontaneous resorption occurs.- - - - - - - - - - ranking = 0.19425471597003keywords = syndrome (Clic here for more details about this article) |
7/76. Adverse effects of dopamine potentiation by long-term treatment with selegiline.A patient with triosephosphate isomerase (TPI) deficiency exhibited worsening of abnormal involuntary movements of the dystonic type and developed psychiatric symptoms while on selegiline. When selegiline was stopped after 9 years of treatment, abnormal involuntary movements improved to pretreatment level and psychiatric behaviour returned to normal. monoamine oxidase-B platelet activity was low in this patient.- - - - - - - - - - ranking = 0.028726420149862keywords = type (Clic here for more details about this article) |
8/76. Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function.We have identified a new mutation in the FBP (fructose 1,6-bisphosphate) aldolase A gene in a child with suspected haemolytic anaemia associated with myopathic symptoms at birth and with a subsequent diagnosis of arthrogryposis multiplex congenita and pituitary ectopia. sequence analysis of the whole gene, also performed on the patient's full-length cDNA, revealed only a Gly346-->Ser substitution in the heterozygous state. We expressed in a bacterial system the new aldolase A Gly346-->Ser mutant, and the Glu206-->Lys mutant identified by others, in a patient with an aldolase A deficit. Analysis of their functional profiles showed that the Gly346Ser mutant had the same Km as the wild-type enzyme, but a 4-fold lower kcat. The Glu206-->Lys mutant had a Km approx. 2-fold higher than that of both the Gly346-->Ser mutant and the wild-type enzyme, and a kcat value 40% less than the wild-type. The Gly346-->Ser and wild-type enzymes had the same Tm (melting temperature), which was approx. 6-7 degrees C higher than that of the Glu206-->Lys enzyme. An extensive molecular graphic analysis of the mutated enzymes, using human and rabbit aldolase A crystallographic structures, suggests that the Glu206-->Lys mutation destabilizes the aldolase A tetramer at the subunit interface, and highlights the fact that the glycine-to-serine substitution at position 346 limits the flexibility of the C-terminal region. These results also provide the first evidence that Gly346 is crucial for the correct conformation and function of aldolase A, because it governs the entry/release of the substrates into/from the enzyme cleft, and/or allows important C-terminal residues to approach the active site.- - - - - - - - - - ranking = 0.11490568059945keywords = type (Clic here for more details about this article) |
9/76. Ex vivo analysis of aberrant splicing induced by two donor site mutations in PKLR of a patient with severe pyruvate kinase deficiency.Two single-nucleotide substitutions in PKLR constituted the molecular basis underlying pyruvate kinase (PK) deficiency in a patient with severe haemolytic anaemia. One novel mutation, IVS5+1G>A, abolished the intron 5 donor splice site. The other mutation, c.1436G>A, altered the intron 10 donor splice site consensus sequence and, moreover, encoded an R479H substitution. We studied the effects on PKLR pre-mRNA processing, using ex vivo-produced nucleated erythroid cells from the patient. Abolition of the intron 5 splice site initiated two events in the majority of transcripts: skipping of exon 5 or, surprisingly, simultaneous skipping of exon 5 and 6 (Delta5,6). Subcellular localization of transcripts suggested that no functional protein was produced by the IVS5+1A allele. The unusual Delta5,6 transcript suggests that efficient inclusion of exon 6 in wild-type PKLR mRNA depends on the presence of splice-enhancing elements in exon 5. The c.1436G>A mutation caused skipping of exon 10 but was mainly associated with a severe reduction in transcripts although these were, in general, normally processed. Accordingly, low amounts of PK were detected in nucleated erythroid cells of the patient, thus correlating with the patient's PK-deficient phenotype. Finally, several low-abundant transcripts were detected that represent the first examples of "leaky-splicing" in PKLR.- - - - - - - - - - ranking = 0.057452840299724keywords = type (Clic here for more details about this article) |
10/76. Dehydrated hereditary stomatocytosis is associated with neonatal hepatitis.Dehydrated hereditary stomatocytosis (DHSt) is an inherited haemolytic anaemia associated with increased red cell membrane permeability to Na(+) and K(+). It is increasingly recognized that a syndrome of self-limiting perinatal ascites can accompany the haemolysis. The cause of the perinatal ascites is unknown, and it has been argued that this could be due to cardiovascular, hepatic or lymphatic problems. We describe the case of a 16-year-old girl who presented neonatally with abnormal liver function tests and ascites. She was extensively investigated at that time. A liver biopsy showed hepatitis and fatty changes. Her ascites resolved within 6 months. At the age of 15 years, she developed an episode of acute haemolysis and was re-investigated. A diagnosis of DHSt was made. Pseudohyperkalaemia, due to ex vivo loss of K(+) from red cells, was present. This study confirms the previously noted association of DHSt, pseudohyperkalaemia and perinatal ascites, and suggests that the latter is of predominantly hepatic origin.- - - - - - - - - - ranking = 0.19425471597003keywords = syndrome (Clic here for more details about this article) |
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