Kinase Deficiency (kinase + deficiency)

Distribution by Scientific Domains


Selected Abstracts


,Two cases of isolated glycerol kinase deficiency with heterogeneous neurological symptoms'

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2007
S Illsinger MD
No abstract is available for this article. [source]


IRAK-4 kinase activity-dependent and -independent regulation of lipopolysaccharide-inducible genes

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2008
Magdalena Koziczak-Holbro
Abstract IRAK-4 kinase inactive (IRAK-4 KD) knock-in mice display defects in TLR- and IL-1 receptor signaling and are resistant to LPS-induced shock. In the present study we examined the LPS-induced response in IRAK-4 KD mice in more detail. We show that IRAK-4 kinase activity is required for certain aspects of TLR-mediated signaling but not for others. We found that IRAK-4 KD cells displayed reduced JNK and p38 signaling, while NF-,B was activated to a normal level but with delayed kinetics compared to wild-type cells. TLR4-mediated IRF3 activation was intact in these cells. Comprehensive analysis of expression of LPS-inducible genes by microarray demonstrated that IRAK-4 KD cells were severely impaired in the expression of many pro-inflammatory genes, suggesting their dependence on IRAK-4 kinase activity. In contrast, the expression of a subset of LPS-induced genes of anti-viral response was not affected by IRAK-4 kinase deficiency. Additionally, we demonstrate that LPS-activated early expression and production of some cytokines, e.g., TNF-,, is partially induced in the absence of IRAK-4 kinase activity. This suggests that the partially unaffected TLR4-mediated signaling could still drive expression of these genes in early phases and that IRAK-4 kinase activity is important for a more sustained anti-bacterial response. See accompanying commentary http://dx.doi.org/10.1002/eji.200838161 [source]


Phosphoglycerate kinase deficiency in two brothers with McArdle-like clinical symptoms

EUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2000
J. Aasly
Phosphoglycerate kinase (PGK) catalyses the transfer of the acylphosphate group of 1,3-diphosphoglycerate to ADP with formation of 3-phosphoglycerate and ATP in the terminal stage of the glycolytic pathway. Two young brothers are presented who both experienced muscle pain, cramps and stiffness shortly after beginning heavy exercise. After these episodes they noticed that the urine was dark brown, indicating rhabdomyolysis and myoglobinuria. The neurological examinations were without remarks. There was no lactate increase in the ischaemic forearm exercise test. Both had very low PGK levels in muscle, erythrocytes, leukocytes and fibroblasts. This is the first family with more than one affected case of PGK deficiency and exercise-induced stiffness, myalgia and rhabdomyolysis. The clinical manifestations may resemble myophosphorylase deficiency (McArdle's disease: glycogenosis Type V) and muscle phosphofructokinase deficiency (Tarui's disease: glycogenosis Type VII). PGK deficiency is inherited as an X-linked trait and may show other features such as mental retardation and/or haemolytic anaemia. [source]


Mutational spectrum and genotype,phenotype correlations in mevalonate kinase deficiency,

HUMAN MUTATION, Issue 8 2006
Saskia H.L. Mandey
Abstract Mevalonate kinase deficiency (MKD) is an autosomal recessive autoinflammatory disorder caused by mutations in the MVK gene resulting in deficient activity of mevalonate kinase (MK). Depending on the clinical severity, MKD may present as hyper-IgD and periodic fever syndrome (HIDS) or the more severe mevalonic aciduria (MA). We analyzed the MVK gene in 57 patients with MKD and found 39 different mutations including 15 novel mutations, expanding the total mutational spectrum of MKD to 63 mutations. To get more insight into the genotype,phenotype correlation in MKD, we studied the effect of selected missense mutations on MK protein stability and activity in various patient fibroblast cell lines. All MKD cell lines showed markedly decreased MK activities that correlated well with the clinical severity and, for most of the cell lines, with the amount of MK protein. When fibroblasts of MKD patients were cultured under conditions known to promote a more controlled protein folding, all cell lines of patients with the HIDS phenotype and few cell lines of patients with the MA phenotype showed an increase in the residual MK activity. This increase in enzyme activity correlates well with an increase in the MK protein levels in these cell lines, indicating that most of the mutations in MKD affect stability and/or folding of the MK protein rather than affecting the catalytic properties of the enzyme. The finding that the residual activity in MKD can be manipulated by environmental conditions may offer therapeutic options to alleviate or prevent the clinical symptoms associated with MKD. Hum Mutat 27(8), 796,802, 2006. © 2006 Wiley-Liss, Inc. [source]


Evaluation of eosin-5-maleimide flow cytometric test in diagnosis of hereditary spherocytosis

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1p2 2010
R. KAR
Summary A flow cytometry-based test using eosin-5-maleimide (EMA) dye was used for diagnosis of hereditary spherocytosis (HS). The mean fluorescence intensiy (MFI) of EMA tagged erythrocytes is lower in HS than that in other hemolytic and nonhemolytic anemias. We enrolled 114 subjects comprising 20 confirmed HS, 20 suspected HS/hemolytic anemia (HA), 20 normal controls, 20 other hemolytic anemias [13 autoimmune hemolytic anemia, three congenital dyserythropoietic anemia (CDA), one pyruvate kinase deficiency, two microangiopathic hemolytic anemia], 18 microcytic anemia and 16 macrocytic anemia cases. All samples were subjected to flow cytometry as per standard protocol. The mean MFI of normal control subjects was 11 861.5 (SD 883.5) and of confirmed HS was 7949.3 (SD 1304.1). Using this test, of 20 patients suspected to be HS/HA but with no confirmatory diagnosis, eight patients were diagnosed as HS. Using logistic regression analysis, the optimum cut-off MFI value between HS and normal controls was 10126. The area under the ROC curve was 0.99. The statistical significance of MFI values was obtained by t -test or Wilcoxon rank sum test as applicable. Compared with normal controls, the MFI values in HS were lower and in megaloblastic anemia were higher which was statistically highly significant (P < 0.01), and the MFI values in CDA were lower which was statistically significant (P < 0.05). False-positive values were obtained in three cases of AIHA and two cases of CDA. The sensitivity and specificity was 96.4% and 94.2% respectively. The EMA-based flow cytometry test is a highly sensitive and specific method for the diagnosis of HS. [source]


AMP-activated protein kinase deficiency exacerbates aging-induced myocardial contractile dysfunction

AGING CELL, Issue 4 2010
Subat Turdi
Summary Aging is associated with myocardial dysfunction although the underlying mechanism is unclear. AMPK, a key cellular fuel sensor for energy metabolism, is compromised with aging. This study examined the role of AMPK deficiency in aging-associated myocardial dysfunction. Young or old wild-type (WT) and transgenic mice with overexpression of a mutant AMPK ,2 subunit (kinase dead, KD) were used. AMPK , isoform activity, myocardial function and morphology were examined. DCF and JC-1 fluorescence probes were employed to quantify reactive oxygen species (ROS) and mitochondrial membrane potential (,,m), respectively. KD mice displayed significantly reduced ,2 but not ,1 AMPK isoform activity at both ages with a greater effect at old age. Aging itself decreased ,1 isoform activity. Cardiomyocyte contractile function, intracellular Ca2+ handling, and SERCA2a levels were compromised with aging, the effects of which were exacerbated by AMPK deficiency. H&E staining revealed cardiomyocyte hypertrophy with aging, which was more pronounced in KD mice. TEM micrographs displayed severe disruption of mitochondrial ultrastructure characterized by swollen, irregular shape and disrupted cristae in aged KD compared with WT mice. Aging enhanced ROS production and reduced ,,m, the effects of which were accentuated by AMPK deficiency. Immunoblotting data depicted unchanged Akt phosphorylation and a significant decrease in mitochondrial biogenesis cofactor PGC-1, in aged groups. AMPK deficiency but not aging decreased the phosphorylation of ACC and eNOS. Expression of membrane Glut4 and HSP90 was decreased in aged KD mice. Moreover, treatment of the AMPK activator metformin attenuated aging-induced cardiomyocyte contractile defects. Collectively, our data suggest a role for AMPK deficiency in aging-induced cardiac dysfunction possibly through disrupted mitochondrial function and ROS production. [source]


Effect of inflammatory attacks in the classical type hyper-IgD syndrome on immunoglobulin D, cholesterol and parameters of the acute phase response

JOURNAL OF INTERNAL MEDICINE, Issue 3 2004
A. Simon
Abstract. Background., Classical type hyper-immunoglobulin D (IgD) syndrome (HIDS) is an hereditary auto-inflammatory disorder, characterized by recurrent episodes of fever, lymphadenopathy, abdominal distress and a high serum concentration of IgD. It is caused by mevalonate kinase deficiency. Objective., To further characterize the acute phase response during fever attacks in HIDS in order to improve diagnosis. Subjects., Twenty-two mevalonate kinase-deficient HIDS patients. Methods., Blood samples were drawn during and in between febrile attacks, and concentrations ofC-reactive protein (CRP), ferritin, procalcitonin, pentraxin 3, IgD and cholesterol in several lipoprotein fractions were determined. Results., The marked acute phase response at the time of a fever attack in classical type HIDS is reflected by a rise in CRP accompanied by a moderate but statistically significant rise in procalcitonin and pentraxin 3. In only two of 22 patients, procalcitonin concentration rose above 2 ng mL,1 during fever attack, compatible with the noninfectious nature of these attacks. Ferritin does not reach the high concentrations found in adult-onset Still's disease. Despite the defect in mevalonate kinase, a component of cholesterol metabolism, serum cholesterol did not change during attacks. IgD concentration is elevated regardless of disease activity, although there is appreciable variation during life. Its role in HIDS remains unclear. Conclusion., The combination of high CRP concentration plus procalcitonin concentration <2 ng mL,1 in a symptomatic HIDS patient might indicate a febrile attack without (bacterial) infection; this observation warrants further investigation for its usefulness as a marker in clinical practice. [source]


Erythrocytic pyruvate kinase deficiency and AB blood types in Australian Abyssinian and Somali cats

AUSTRALIAN VETERINARY JOURNAL, Issue 1-2 2009
VR Barrs
Objective,, To determine the frequency of the mutant pyruvate kinase (PK) allele, haematological parameters and AB blood types of Abyssinian and Somali cats in Australia. Design,, Complete blood cell and reticulocyte counts, DNA PK mutation testing and blood typing were performed in all cats. Results,, A total of 60 cats (36 Abyssinians, 24 Somalis) were included (37 females, 23 males). For the mutant PK allele, three female Somalis were homozygous (affected, 5%), 17 cats were heterozygous (carrier, 28%) and 40 cats tested negative (normal, 67%). Pedigree analysis revealed common ancestry of affected and many carrier cats. Of affected cats, two had regenerative anaemias and all had reticulocytosis (range 64,390 × 109/L; P < 0.001 compared with normal or carrier cats). The only consistent historical sign was lethargy. One affected cat was euthanased 18 months after testing, because of anaemia, neutropenia, anorexia and weight loss. The mutant allele frequency was 0.19 overall (0.29 in Somalis, 0.13 in Abyssinians). All cats had blood type A. The commercial blood typing card method incorrectly identified 12 cats as having type AB blood. Conclusions,, The frequency of the mutant PK allele is high in Australia. Screening for PK deficiency is indicated before mating and in individual cats of these breeds, even in the absence of anaemia and especially when there is reticulocytosis. Although all cats in the present study had blood type A, blood type B is common in these breeds worldwide. Retyping of any AB typed cats by a laboratory technique is recommended. [source]


Paravertebral extramedullary haemopoiesis associated with pyruvate kinase deficiency

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2009
Rupert Hipkins
No abstract is available for this article. [source]


Fetal bradycardia at 28 weeks of gestation associated with cardiac glycogen phosphorylase b kinase deficiency

ACTA PAEDIATRICA, Issue 11 2003
C Bührer
No abstract is available for this article. [source]