1/9. Coexistence of congenital red cell pyruvate kinase and band 3 deficiency.The authors report the case of a 9-year-old Caucasian girl, born in northern portugal, with chronic nonspherocytic haemolytic anaemia and without family history of anaemia. The aethiological study of this anaemia revealed pyruvate kinase deficiency (PKD), because of two previously described mutations (426Arg-->Trp and 510Arg-->Gln). Since the blood smear revealed features not fully compatible with PKD diagnosis, additional tests were performed for the propositus and her parents, namely red blood cell membrane protein analysis. A decrease in proteins band 3 (15%) and 4.2 (18%) was found in the propositus. Her father presented only a decrease in band 3 (11%). Coexistence of PKD and erythrocyte membrane proteins deficiency in the same patient is very uncommon. Our findings suggest that a careful blood smear observation may lead to the identification of a combined deficiency in erythrocyte membrane proteins and enzymopathies.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
2/9. Unexpectedly high but still asymptomatic iron overload in a patient with pyruvate kinase deficiency.iron overload is a serious condition, which may lead to irreversible organ damage. The risk of iron accumulation in pyruvate kinase deficiency (PKD) has traditionally been regarded as low, but recent evidence has questioned this notion. We here present a case of a young PKD patient showing evidence of asymptomatic iron accumulation measured as liver iron concentration (LIC) obtained noninvasively by magnetic resonance imaging. The iron overload was not related to blood transfusions, but rather secondary to concomitant risk factors leading to increased intestinal iron absorption, such as chronic hemolysis and splenectomy. The iron status of PKD patients, preferably assessed by LIC measurements, should therefore be evaluated regularly also in asymptomatic patients. This evaluation should start already at a young age, in order to initiate iron chelation before the development of iron-induced organ damage.- - - - - - - - - - ranking = 0.71428571428571keywords = deficiency (Clic here for more details about this article) |
3/9. Deficiency of the alpha and beta subunits of pyruvate dehydrogenase in a patient with lactic acidosis and unexpected sudden death.An infant with moderate muscular hypotonia and congenital lactic acidosis died suddenly at the age of 3 months. autopsy revealed no abnormalities responsible for this unexpected death. Measurement of mitochondrial enzymes involved in energy production indicated a severely decreased total pyruvate dehydrogenase complex (PDHC) activity in muscle tissue (0.23 nmoles x min-1 x mg protein-1, control range 2.8-8.7) and moderately decreased PDHC activity in fibroblasts (0.27 nmoles x min-1 x mg protein-1, control range 0.37-2.32). The activity of the first component E1 (pyruvate dehydrogenase) in muscle tissue was 10 times lower than that of controls (0.008 nmoles x min-1 x mg protein-1, control range 0.10-0.25). The activities of dihydrolipoyl dehydrogenase (E3) and various other mitochondrial enzymes were normal. Immunochemical analysis in skeletal muscle tissue and fibroblasts demonstrated a decrease in the amount of the alpha and beta subunits of E1. The features of this patient are compared with those of other patients reported in the literature with immunochemically confirmed combined E1 alpha and beta deficiency.- - - - - - - - - - ranking = 0.14285714285714keywords = deficiency (Clic here for more details about this article) |
4/9. diagnosis of pyruvate kinase deficiency in a transfusion-dependent patient with severe hemolytic anemia.In a 2-yr old girl a hemolytic anemia was present since birth requiring multiple blood transfusions. pyruvate kinase deficiency was suspected on the basis of a marginal enzyme activity, but could not be established due to the presence of massive numbers of donor cells in her peripheral blood. However, by density fractionation we succeeded in the isolation of a small fraction of the patient's own cells, in which a severe pyruvate kinase deficiency could be detected. In contrast hexokinase and glucose-6-phosphate dehydrogenase activities were extremely high, which is indicative that a very immature cell population is present in this fraction. In immunofluorescence studies a clear crossreaction was apparent with anti M2-type pyruvate kinase antibodies, whereas only a faint reaction with anti L-type could be detected. Despite the presence of a slight amount of L-type immunoreactive material, the residual activity in the patient's cell fraction could only be attributed to M2-type pyruvate kinase as was shown by cellulose acetate electrophoresis.- - - - - - - - - - ranking = 0.85714285714286keywords = deficiency (Clic here for more details about this article) |
5/9. Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia.A 2-day-old girl developed a severe lactic acidosis with a normal lactate/pyruvate ratio and hyperammonaemia. plasma arginine and citrulline levels were below the limit of detection. In muscle total pyruvate dehydrogenase complex (PDHC) and pyruvate decarboxylase (E1) activities were reduced to a fraction of lower control values. The acute neonatal period was bridged with peritoneal dialysis, dichloroacetate therapy, supplements of arginine and branched chain amino acids, a complete vitamin b complex and lipoic acid. Lactate homeostasis responded to pharmacological supplements of lipoic acid. At age 1 year the child was hypotonic, showed severe developmental retardation, optic atrophy and cranial dysmorphism. She died aged 1 year 8 months with signs of respiratory paralysis but with normal lactate levels under assisted breathing. Pathological findings at autopsy were suggestive of Leigh syndrome, interstitial pneumonia and extensive fatty infiltration of hepatocytes. regression analysis of data from 187 plasma amino acid determinations from the patient over a period of 1 year 8 months revealed a persistent-imbalance involving alanine, glutamic acid, glutamine, proline, citrulline and branched chain amino acids. Aspects of acute and long-term therapy in this patient and some implications of the imbalances in plasma amino acids are discussed.- - - - - - - - - - ranking = 7.5930751876389keywords = carboxylase, deficiency (Clic here for more details about this article) |
6/9. mutation of the E1 alpha subunit of the pyruvate dehydrogenase complex, in relation to heterogeneity.pyruvate dehydrogenase complex was studied using bio- and immunochemical methods in cultured cells derived from two patients with the severe type and one patient with the mild type of pyruvate dehydrogenase complex deficiency. In patients 1 and 2, enzyme activity was all but undetectable and associated with the absence of E1 alpha subunit of the complex. Patient 3 had a slightly reduced level of enzyme activity, and this was associated with a larger form of E1 alpha subunit. The amount and size of E1 alpha mRNA in the three patients was similar to that of control samples. Thus, the severity of E1 alpha deficiency in these three patients is likely to depend on the type of mutation in the pyruvate dehydrogenase E1 alpha subunit and the synthesis and degradation rate of the subunit.- - - - - - - - - - ranking = 0.28571428571429keywords = deficiency (Clic here for more details about this article) |
7/9. pyruvate carboxylase deficiency: acute exacerbation after ACTH treatment of infantile spasms.pyruvate carboxylase deficiency results in congenital lactic acidosis. We report the significant finding in a child with infantile spasms controlled with adrenocorticotrophin hormone (ACTH) but who then developed severe lactic acidosis; pyruvate carboxylase deficiency was subsequently diagnosed. blood lactate, pyruvate, and alanine levels were elevated, as well as cerebrospinal fluid alanine. plasma alanine concentration was doubled by ACTH therapy. fibroblasts contained extremely low pyruvate carboxylase activity. The patient died at 12 weeks of age after recurrent episodes of profound acidosis. At autopsy, the brain manifested cystic degeneration and demyelination. pyruvate carboxylase deficiency is associated with neonatal onset of acidosis, delayed development, seizures, hypotonia, recurrent profound acidosis, and early death. The dramatic rise in plasma alanine content coincident with ACTH therapy suggest that ACTH played a role in precipitating the catastrophic metabolic acidosis.- - - - - - - - - - ranking = 591.03184704515keywords = carboxylase deficiency, carboxylase, deficiency (Clic here for more details about this article) |
8/9. Erythrocyte pyruvate kinase deficiency. A case of severe congenital hemolytic anemia.Although it occurs rarely, erythrocyte pyruvate kinase deficiency is a cause of neonatal jaundice and anemia across many ethnic and geographic groups. In this report of a missouri case, an infant with this condition was also found to have Pelger-Huet leukocyte anomaly.- - - - - - - - - - ranking = 0.71428571428571keywords = deficiency (Clic here for more details about this article) |
9/9. Transient improvement of congenital lactic acidosis in a male infant with pyruvate decarboxylase deficiency treated with dichloroacetate.A comatose male newborn infant with congenital lactic acidosis caused by pyruvate decarboxylase deficiency was treated with dichloroacetate (DCA), which stimulated an 88% drop in serum lactate concentration and reversed his coma. The response to DCA was temporary and the lactic acidosis worsened until his death, but DCA may confer more lasting benefit in less severely affected infants.- - - - - - - - - - ranking = 417.15014316353keywords = carboxylase deficiency, carboxylase, deficiency (Clic here for more details about this article) |