I Deficiency (i + deficiency)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Influence of factor IX on overall plasma coagulability and fibrinolytic potential as measured by global assay: monitoring in haemophilia B

HAEMOPHILIA, Issue 1 2008
N. A. GOLDENBERG
Summary., We sought to determine the influence of factor IX (FIX) deficiency upon overall coagulative and fibrinolytic capacities in plasma using the clot formation and lysis (CloFAL) assay, and to investigate the role of this global assay as an adjunctive monitoring tool in haemophilia B. CloFAL assay parameters were measured in vitro in platelet-poor plasma in relation to FIX activity and antigen (FIX:Ag), and were determined ex vivo among FIX-deficient patients (n = 41) in comparison to healthy individuals (n = 48). Supplementation of FIX-deficient plasma with FIX in vitro demonstrated a non-linear concentration dependence of FIX upon overall plasma coagulability. Ex vivo, coagulability was significantly decreased in FIX-deficient vs. healthy subjects among adults [median coagulation index (CI): 4% vs. 104% respectively; P < 0.001] and children (median CI: 9% vs. 63%; P < 0.001). Fibrinolytic capacity was increased in adult FIX-deficient vs. healthy subjects (median fibrinolytic index: 216% vs. 125%, respectively, P < 0.001), and was supported by a trend in shortened euglobulin lysis time (ELT). Severe haemophilia B patients showed heterogeneity in aberrant CloFAL assay waveforms, influenced partly by FIX:Ag levels. Patients with relatively preserved FIX:Ag (i.e. dysfunctional FIX) exhibited a shorter time to maximal amplitude in clot formation than those with type I deficiency. During patient treatment monitoring, markedly hypocoagulable CloFAL assay waveforms normalized following 100% correction with infused FIX. The CloFAL global assay detects FIX deficiency, demonstrates differences in coagulability between dysfunctional FIX and type I deficiency, and appears useful as an adjunctive test to routine FIX measurement in monitoring haemophilia B treatment. [source]


Amantadine for levodopa-induced choreic dyskinesia in compound heterozygotes for GCH1 mutations

MOVEMENT DISORDERS, Issue 10 2004
Yoshiaki Furukawa MD
Abstract Amantadine suppressed severe levodopa-induced choreic dyskinesia, which developed at initiation of levodopa therapy, in two siblings manifesting dystonia with motor delay phenotype of GTP cyclohydrolase I deficiency caused by compound heterozygous GCH1 mutations. Our finding suggests a beneficial effect of amantadine on this type of dyskinesia frequently observed in relatively severe dopamine-deficient metabolic disorders. © 2004 Movement Disorder Society [source]


Carbamoyl phosphate synthetase I deficiency: molecular genetic findings and prenatal diagnosis

PRENATAL DIAGNOSIS, Issue 8 2001
Tsutomu Aoshima
Abstract We report a Japanese boy who died at Day 28 of life because of severe carbamoyl phosphate synthetase I (CPS1) deficiency that was proven by enzyme assay. By analysis of cDNA and genomic DNA, he was shown to be a compound heterozygote with two point mutations of the CPS1 gene, 840G>C leading to an aberrant splicing and 1123C>T (predicting Q375X). The 840G>C was a mutation described in another Japanese family. Since his parents carried each mutation heterozygously, we performed prenatal diagnosis at 16 weeks of his mother's next gestation by multiplex PCR and melting curve analysis in a single capillary containing two-color fluorescent (LC-Red 640 and LC-Red 705) probes on LightCycler. We analyzed genomic DNA extracted from amniotic cells and found that the fetus was homozygous for the wild-type alleles. At term a healthy girl was born without hyperammonemia. Copyright © 2001 John Wiley & Sons, Ltd. [source]


X-linked NDUFA1 gene mutations associated with mitochondrial encephalomyopathy

ANNALS OF NEUROLOGY, Issue 1 2007
Daniel Fernandez-Moreira PharmB
Objective Mitochondrial complex I deficiency is the commonest diagnosed respiratory chain defect, being genetically heterogeneous. The male preponderance of previous patient cohorts suggested an X-linked underlying genetic defect. We investigated mutations in the X-chromosomal complex I structural genes, NDUFA1 and NDUFB11, as a novel cause of mitochondrial encephalomyopathy. Methods We sequenced 12 nuclear genes and the mitochondrial DNA,encoded complex I genes in 26 patients with respiratory chain complex I defect. Novel mutations were confirmed by polymerase chain reaction restriction length polymorphism. Assembly/stability studies in fibroblasts were performed using two-dimensional blue native gel electrophoresis. Results Two novel p.Gly8Arg and p.Arg37Ser hemizygous mutations in NDUFA1 were identified in two unrelated male patients presenting with Leigh's syndrome and with myoclonic epilepsy and developmental delay, respectively. Two-dimensional blue native gel electrophoresis showed decreased levels of intact complex I with no accumulation of lower molecular weight subcomplexes, indicating that assembly, stability, or both are compromised. Interpretation Mutations in the X-linked NDUFA1 gene result in complex I defect and encephalomyopathy. Assembly/stability analysis might give an explanation for the different clinical phenotypes and become useful for future diagnostic purposes. Ann Neurol 2007;61:73,83 [source]


Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease

ANNALS OF NEUROLOGY, Issue 4 2003
Denise M. Kirby BSc(Hons)
Respiratory chain complex I deficiency is a common cause of Leigh's disease (LD) and can be caused by mutations in genes encoded by either nuclear or mitochondrial DNA (mtDNA). Most pathogenic mtDNA mutations act recessively and only cause disease when present at high mutant loads (typically >90%) in tissues such as muscle and brain. Two mitochondrial DNA mutations in complex I subunit genes, G14459A in ND6, and T12706C in ND5, have been associated with complex I deficiency and LD. We report another ND5 mutation, G13513A, in three unrelated patients with complex I deficiency and LD. The G13513A mutation was present at mutant loads of approximately 50% or less in all tissues tested, including multiple brain regions. The threshold mutant load for causing a complex I defect in cultured cells was approximately 30%. Blue Native polyacrylamide gel electrophoresis showed that fibroblasts with 45% G13513A mutant load had approximately 50% of the normal amount of fully assembled complex I. Fibroblasts with greater than 97% of the ND6 G14459A mutation had only 20% fully assembled complex I, suggesting that both mutations disrupt complex I assembly or turnover. We conclude that the G13513A mutation causes a complex I defect when present at unusually low mutant load and may act dominantly. [source]


Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors , a multicentre case,control study

BRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2000
Christine Heller
The factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, the methylenetetrahydrofolate reductase (MTHFR) T677T genotype, together with fasting homocysteine (HCY) concentration, lipoprotein (Lp)(a), anti-thrombin (AT), protein C (PC), protein S (PS) and anti-cardiolipin antibodies were investigated in 65 consecutively recruited infants (neonate to <,12 months) with renal venous thrombosis (RVT; n = 31), portal vein thrombosis (PVT; n = 24) or hepatic vein thrombosis (HVT n = 10), and 100 age- and sex-matched healthy controls. FV G1691A was found in 14 babies (heterozygous: RVT n = 9, PVT n = 4; homozygous HVT n = 1) and five controls, the MTHFR TT677 genotype together with increased HCY in four infants with thrombosis (RVT n = 2; PVT n = 1; HVT n = 1) compared with one control, and the PT G20210A variant was present in one control only. PC type I deficiency was diagnosed in three patients (RVT n = 2; PVT n = 1) and AT deficiency in two patients (RVT n = 1; PVT n = 1). Three neonates with spontaneous thrombosis showed FV G1691A combined with Lp(a) and the FV G1691A was combined with the PT G20210A genotype in two infants. Additional triggering factors were reported in 27 patients (41·5%). The overall odds ratios (ORs) and 95% confidence intervals (CIs) with respect to the different thrombosis locations were: RVT (OR/CI: 10·9/3·85,31·1; P < 0·0001), PVT (5·47/1·7,17·6; P < 0·0007) and HVT (3·3/0·58,18·7; P = 0·18). The data presented here suggest that genetic prothrombotic risk factors also play an important role in abdominal venous thrombosis during infancy. [source]