1/61. Hb chile [beta28(B10)Leu-->Met]: an unstable hemoglobin associated with chronic methemoglobinemia and sulfonamide or methylene blue-induced hemolytic anemia.Among the causes of life-long cyanosis are congenital methemoglobinemia due to M hemoglobins, congenital methemoglobinemia due to methemoglobin reductase deficiency, a small number of low oxygen affinity hemoglobins, and a small number of unstable hemoglobins that spontaneously form methemoglobin in vivo at an accelerated rate. We report an unstable hemoglobin with these characteristics that was observed in a family of indigenous (native American) origin living near Santiago, chile. This variant has the substitution beta28(B10)Leu-->Met, unambiguously corresponding to the dna mutation of CTG-->ATG in beta-globin gene codon 28.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
2/61. A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia.Recessive congenital methemoglobinemia due to nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) deficiency is classified into 2 clinical types: type 1 (erythrocyte type) and type 2 (generalized type). We found a Chinese family with type 1 recessive congenital methemoglobinemia, the patients from which were diagnosed according to clinical symptoms and b5R enzyme activity in the blood cells. To learn the molecular basis of type 1 recessive congenital methemoglobinemia in this Chinese family, we isolated total rna from the peripheral leukocytes of the propositus and b5R complementary dna (cDNA) by reverse transcription- polymerase chain reaction (RT-PCR). The coding region of the b5R cDNA was analyzed by sequencing the cloned PCR products. The results showed that the propositus was homozygous for a G-->A transition at codon 203 in exon 7, changing a cysteine to a tyrosine (Cys203Tyr). To characterize the mutant enzyme, both glutathione S-transferase (GST)-fused wild-type b5R and GST-fused mutant Cys203Tyr b5R were expressed in escherichia coli and affinity purified. The results showed that the catalytic activity of the enzyme was not much affected by this amino acid substitution, but the mutant enzyme exhibited decreased heat stability and increased susceptibility to trypsin. These properties of the mutant enzyme would account for the restricted b5R deficiency and mild clinical manifestations of these type 1 patients. The finding of this novel mutation makes codon 203 the only position within the b5R gene at which more than 1 mutation has been found.- - - - - - - - - - ranking = 2keywords = deficiency (Clic here for more details about this article) |
3/61. A case of methemoglobinemia type II due to NADH-cytochrome b5 reductase deficiency: determination of the molecular basis.Clinical, biochemical and molecular findings in a patient with methemoglobinemia type II are described. Furthermore, a comparison between methemoglobinemia type I and type II, both caused by a deficiency of NADH-cytochrome b5 reductase (b5R), is made. Although the clinical pictures of type I and II are strikingly different, mutations in the diaphorase (DIA1) gene located on chromosome 22 have been described in both types. In the present patient, two newly identified mutations, both leading to a stop codon in exon 4 (Gln77Ter) and in exon 6 (Arg160Ter), were found. Identification of different mutations at different positions in the DIA1 gene might shed light on the clinical and biochemical differences between methemoglobinemia type I and type II.- - - - - - - - - - ranking = 5keywords = deficiency (Clic here for more details about this article) |
4/61. A Thai boy with hereditary enzymopenic methemoglobinemia type II.Individuals with methemoglobin exceeding 1.5 g/dl have clinically obvious central cyanosis. Hereditary methemoglobinemia is due either to autosomal dominant M hemoglobins or to autosomal recessive enzymopenic methemoglobinemia. Four types of enzymopenic methemoglobinemia have been described. In addition to methemoglobinemia, individuals with type II, which is the generalized cytochrome b5 reductase deficiency, have severe and progressive neurological disabilities. Here we report a 3-year-old Thai boy with type II hereditary enzymopenic methemoglobinemia. He was born to a second-cousin couple. His central cyanosis was first observed around 10 months of age. His neurological abnormalities were seizures beginning at 1 year of age, microcephaly, and inability to hold his head up. His cardiovascular and pulmonary evaluations were unremarkable. Methemoglobin level by spectral absorption pattern was 18 per cent. A qualitative enzymatic assay confirmed the deficiency of the cytochrome b5 reductase enzyme. With this definite diagnosis, a prenatal diagnosis for the next child of this couple will be possible.- - - - - - - - - - ranking = 2keywords = deficiency (Clic here for more details about this article) |
5/61. Molecular basis of recessive congenital methemoglobinemia, types I and II: Exon skipping and three novel missense mutations in the NADH-cytochrome b5 reductase (diaphorase 1) gene.Hereditary methemoglobinemia due to reduced nicotin amide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5r) deficiency is classified into an erythrocyte type (I) and a generalized type (II). We investigated the b5r gene of three unrelated patients with types I and II and found four novel mutations. The patient with type I was homozygous for a c.535 G-->A exchange in exon 6 (A179T). The patients with type II were found to be homozygous for a c.757 G-->A transition in exon 9 (V253M) and compound heterozygous for two mutations, respectively. One allele presented a c.379 A-->G transition (M127V). The second allele carried a sequence difference at the invariant 3' splice-acceptor dinucleotide of intron 4 (IVS4-2A-->G) resulting in skipping of exon 5. To characterize a possible effect of this mutation on rna metabolism, poly(A)( ) rna was analyzed by RT-PCR and sequencing. The results show that rna is made from the allele harboring the 3'-splice site mutation. Furthermore, western blot analysis revealed a complete absence of immunologically detectable b5r in skin fibroblasts of this patient. The compound heterozygosity for the splice site and the missense mutations apparently caused hereditary methemoglobinemia type II in this patient. Hum Mutat 17:348, 2001.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
6/61. Haemolytic anaemia after oral self-giving of naphthalene-containing oil.A clinical case of suicide attempt by means of oral self-giving of naphthalene-containing oil in an old man was reported. Clinical features showed haemolytic anaemia supported by a decrease of haemoglobin concentration and red blood cell count, an increase of bilirubin (prevalently indirect) and lactate dehydrogenase and very low levels of haptoglobin. Methaemoglobin (metHb) measured at admission to the Emergency Room and 19 days after poisoning was still above normal limits. No deficiency of glucose-6-phosphate dehydrogenase was detected. The clinical manifestations ameliorated after treatment with concentrated red blood cells and ascorbic acid, with fast normalization of metHb. The clinical picture appeared almost normal 1 month after poisoning. The clinical diagnosis was 'haemolytic anaemia caused by naphthalene'. Absence of glucose-6-phosphate dehydrogenase deficiency probably reduced the severity of poisoning.- - - - - - - - - - ranking = 41.789144072521keywords = dehydrogenase deficiency, dehydrogenase, deficiency (Clic here for more details about this article) |
7/61. Hemolytic anemia after methylene blue therapy for aniline-induced methemoglobinemia.methylene blue is utilized as the main treatment of methemoglobinemia conventionally, but it may be ineffective in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a G6PD-deficient patient who suffered from aniline-induced methemoglobinemia with initial good response Heinz body but hemolytic anemia appeared later 3 d after methylene blue therapy. G6PD deficiency was identified. He recovered uneventfully with hydration, packed blood transfusion and adjuvant luvela-N(dl-alpha-tocopheryl nicotinate) medication. Caution should be taken in using methylene blue as antidote of acute methemoglobinemia, especially when a history of G6PD deficiency is obscure.- - - - - - - - - - ranking = 6.4987811039736keywords = dehydrogenase, deficiency (Clic here for more details about this article) |
8/61. Cyanotic child--can it be methaemoglobinemia?Methaemoglobinemia is a rare condition and can give surprise in emergency setup. We have encountered one such case in emergency recently that presented with both peripheral and central cyanosis without cardio-respiratory compromise. The patient was confirmed to be suffering from methaemoglobinemia due to antimalarials that he had received before coming to the hospital. cyanosis due to methaemoglobinemia in our patient was precipitated by concomitant glucose 6-phosphate dehydrogenase (G6PD) deficiency. The patient was managed with conservative management and vitamin C administration.- - - - - - - - - - ranking = 4.4987811039736keywords = dehydrogenase, deficiency (Clic here for more details about this article) |
9/61. Eight blue babies.methemoglobinemia is a serious medical condition that affects hundreds of infants in the united states each year. The condition involves the oxidation of red cell hemoglobin to a state that is unable to transport oxygen. Affected infants appear cyanotic and may have altered mental status. The condition is readily reversible if recognized and treated appropriately. The wisconsin Division of public health investigates all cases of infant methemoglobinemia in an attempt to determine their cause. Between January 1990 and September 1999, 8 infants were diagnosed with this condition. review of their hospitalization records found that 3 of these cases involved infants whose formula was prepared with water from nitrate-contaminated wels. risk factors identified in the remaining cases included use of folk remedies, misuse of over-the-counter analgesics, and an inherited enzyme deficiency. Causes were not identified for 2 of the cases. All of the affected infants recovered.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
10/61. Congenital methemoglobinemia due to NADH-methemoglobin reductase deficiency in three Indian families.Congenital methemoglobinemia is a relatively rare clinical disorder characterized by life-long cyanosis, caused by either an inherited mutant hemoglobin (Hb-M) or deficiency of physiologically active NADH-dependent methemoglobin reductase (NADH-MR). NADH-MR deficiency leads to two different types of recessive congenital methemoglobinemia. In type I, cyanosis is the only major symptom and NADH-MR deficiency is restricted only to the red blood cells. In type II, cyanosis is associated with severe mental retardation and neurological impairment. The objective of this study is to establish the cause of cyanosis in our cases of congenital methaemoglobinemia. Erythrocyte NADH-MR activity was assayed spectrophotometrically. Spectral analysis of the hemolysate treated with potassium ferricyanide was recorded between 400-700 nm and Hb electrophoresis on starch gel at pH 7.0 was done to rule out the presence of Hb-M. NADH-MR deficiency was detected in 3 families. There was a history of consanguinity in one of these cases. The three propositi presented with breathlessness, fever and peripheral cyanosis. There was no history of cardiac illness or exposure to drugs and chemicals. There were no signs and symptoms of mental retardation. The presence of Hb-M was ruled out. Hb-A2, Hb-F, G6PD activity and reduced glutathione levels were normal. NADH-MR activity in all the cases ranged from 4.1 to 9.2 IU/g Hb (normal range 7.0-24.0 IU/g Hb). We describe NADH-MR deficiency in three unrelated cases (age 4 months to 6 years) where the activity of the enzyme was 30-40% of normal. These three cases of congenital methemoglobinemia are due to type-I NADH-MR deficiency without mental retardation.- - - - - - - - - - ranking = 10keywords = deficiency (Clic here for more details about this article) |
| | Next -> |