1/208. Familial pseudohyperkalemia maps to the same locus as dehydrated hereditary stomatocytosis (hereditary xerocytosis). Familial pseudohyperkalemia is a "leaky red blood cell" condition in which the cells show a temperature-dependent loss of potassium (K) from red blood cells when stored at room temperature, manifesting as apparent hyperkalemia. The red blood cells show a reduced lifespan in vivo but there is no frank hemolysis. Studies of cation content and transport show a marginal increase in permeability at 37 degrees C and a degree of cellular dehydration, qualitatively similar to the changes seen in dehydrated hereditary stomatocytosis (hereditary xerocytosis). Physiological studies have shown that the passive leak to K has an abnormal temperature dependence, such that the leak is less sensitive to temperature than that in normal cells. We performed genetic mapping on the original family and found that the condition in this kindred maps to the same locus (16q23-ter) that we have previously identified for an Irish family with dehydrated hereditary stomatocytosis, which does not show the same temperature effects. ( info) |
2/208. 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. ( info) |
| portal vein thrombosis is a rare but potentially lethal complication in children requiring splenectomy. We report on a 15-year-old boy with a dehydrated hereditary stomatocytosis, who underwent splenectomy and presented a postoperative partial portal vein thrombosis. With prompt heparin therapy, neither propagation of the thrombus nor further cavernous transformation in the following occurred 6 years. CONCLUSION: Recent data suggest that hereditary stomatocytosis carries a high risk of thrombotic complications, especially after splenectomy. This procedure, the benefit of which is limited in this condition, should therefore be strongly avoided. ( info) |
4/208. Fetal schistocytic hemolytic anemia and umbilical vein varix. A rare case of schistocytic hemolytic anemia presenting in a fetus secondary to a varix of the intra-abdominal umbilical vein is reported. A patient was referred to our hospital at 32 weeks of gestation because of an abnormal hypoechoic finding in the fetal liver. Prenatal ultrasound showed turbulent flow through a 12-mm diameter dilatation of the fetal intra-abdominal umbilical vein consistent with a varix. cardiomegaly also was noted. At birth, the 1098-g, growth-retarded, male neonate was in severe congestive heart failure secondary to anemia as the initial hemoglobin was 5 g/dL. Additional evaluation found the anemia to be secondary to schistocytic hemolysis. After the neonate received a transfusion of packed erythrocytes and supportive care, the anemia quickly resolved, and he was discharged to home doing well after a 6-week stay in the neonatal intensive care unit. Prompt recognition of the varix prenatally and thorough evaluation of the newborn postnatally led to appropriate diagnosis and treatment. ( info) |
5/208. Hemoglobin Moabit: alpha 86 (F7) Leu leads to Arg: a new unstable abnormal hemoglobin. A new alpha chain abnormal hemoglobin variant was found in a Turkish patient with a mild Heinz body hemolytic anemia and splenomegaly. The substitution alpha 86 Leu leads to Arg, which is next to the heme binding proximal histidine, is responsible for a marked instability of the molecule. The oxygen affinity of the erythrocytes was found to be slightly decreased. ( info) |
6/208. Neonatal lupus erythematosus with microvascular hemolysis. A female, term newborn born to a mother with a history of idiopathic thrombocytopenic purpura and antinuclear antibodies, single-stranded A antibody, and IgM anticardiolipin antibodies presented with immune thrombocytopenia, disseminated intravascular coagulation (DIC), microangiopathic hemolytic anemia, and a characteristic lupus rash in the periorbital areas. She responded to combined treatment with dexamethasone and intravenous immunoglobulin (IVIG). At age 9 months, she was readmitted with severe thrombocytopenia, DIC, and microangiopathic hemolytic anemia. She again responded to IVIG. This suggests that microangiopathic hemolysis can be a presenting symptom in neonatal lupus erythematosus and that reoccurrence of the microangiopathic hemolysis may occur even after the disappearance of lupus antibodies. ( info) |
7/208. Haemolytic disease of the newborn due to anti-Ce. A baby was readmitted to the hospital 3 days after delivery when she developed jaundice. At admission, the direct antiglobulin test was also found to be positive. The baby required emergency exchange transfusion. A strongly reacting IgG anti-Ce (Rh7) was found in the serum of the mother. Severe haemolytic disease of the newborn due to anti-Ce is very rare. The mother's serum had been screened and found negative for red cell antibodies at 16 weeks gestation but the test was not repeated later in pregnancy when this antibody might have been detected. ( info) |
8/208. Identification of an erythrocyte pyruvate kinase variant in a family from Latium with non-spherocytic congenital haemolytic anaemia. Erythrocyte PK deficiency was detected in a family from Latium in italy. This PK variant is characterized by normal or increased activity immediately after blood collection, instability to storage, to heat and to urea. Only in the propositus the mutant enzyme exhibited an increased Michaelis constant for PEP, slightly increased inhibition by ATP and an altered optimum pH value. The kinetic anomaly was only partially corrected by activation with F-1, 6-DP and by addition of 2-ME. From these results it can be concluded that in the family observed two distinct erythrocyte PK alterations were demonstrable: instability in the propositus and his father; low affinity for PEP and altered optimum pH value only in the propositus. ( info) |
9/208. 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 ( info) |
10/208. Hb Mont Saint Aignan [beta128(H6)Ala-->Pro]: a new unstable variant leading to chronic microcytic anemia. Hb Mont Saint-Aignan [beta128(H6)Ala-->Pro] is a mildly unstable variant, associated with hemolytic anemia, marked microcytosis and increased alpha/beta biosynthetic ratio (1.55 versus 1.1 /- 0.1 in the control). The abnormal chain was isolated by selective precipitation with isopropanol and the structural modification determined by protein chemistry methods (reversed phase high performance liquid chromatography and mass spectrometry). Possible mechanisms underlying the beta( )-thalassemia-like expression of this variant are discussed. ( info) |