1/29. prolidase deficiency among an Israeli population: prenatal diagnosis in a genetic disorder with uncertain prognosis.prolidase deficiency is an autosomal recessive disorder that is characterized by considerable inter- and intrafamilial variability in its clinical presentation, ranging from asymptomatic to severe and fatal illness. We report here, for the first time, prenatal diagnosis of prolidase deficiency in a family whose first child was severely affected since birth and died at an early age. However, unexpectedly, the parents decided to continue the second pregnancy, which produced a full-term, healthy-appearing baby. The diagnosis of severe prolidase deficiency was confirmed in the baby's leukocytes. At age 4 months the baby is asymptomatic. Since the clinical severity of the disorder cannot be predicted, genetic counselling remains problematic despite the feasibility of prenatal diagnosis.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
2/29. Neonatal purpura fulminans due to homozygous protein c deficiency.Severe and recurrent purpura fulminans developed in a Turkish boy at 1 week of age. Initial coagulation studies performed were compatible with disseminated intravascular coagulation. Subsequent investigations showed that the patient had homozygous and his healthy parents had heterozygous protein c deficiency. The episodes of purpura fulminans were controlled by infusions of fresh frozen plasma and heparinization. Oral anticoagulant therapy was given in the symptom-free period.- - - - - - - - - - ranking = 0.71428571428571keywords = deficiency (Clic here for more details about this article) |
3/29. Congenital transcobalamin II deficiency due to errors in rna editing.Transcobalamin II (TCII) is a plasma protein essential for the transport and cellular uptake of vitamin B12 (B12; cobalamin, Cbl). Congenital deficiency of functional TCII is an autosomal recessive genetic disorder that results in clinical B12 deficiency usually within several months following birth. In this report, we describe the molecular basis for TCII deficiency in two patients who developed a megaloblastic anemia in early infancy. The serum of both patients contained immunoreactive TCII that did not bind [57Co]Cbl. The fibroblasts from each patient secreted a similarly nonfunctional TCII, yet full-length TCII transcripts were identified by Northern blot. Overlapping cDNA fragments were generated by reverse transcription-polymerase chain reaction and several mutations were identified in the coding region of the cDNA, one of which was common to both patients. However, amplification of the corresponding regions of the gene from genomic dna failed to identify these mutations. These findings were confirmed by replicate analyses and support the proposal that a variance in rna editing is the likely mechanism for the mutations that resulted in the expression of a nonfunctional TCII protein in these patients.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
4/29. Null mutations in the N-acetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia.N-acetylglutamate synthase (NAGS) is a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate, an essential allosteric activator of carbamyl phosphate synthetase I, the first enzyme of the urea cycle. liver NAGS deficiency has previously been found in a small number of patients with hyperammonemia. The mouse and human NAGS genes have recently been cloned and expressed in our laboratory. We searched for mutations in the NAGS gene of two families with presumed NAGS deficiency. The exons and exon/intron boundaries of the NAGS gene were sequenced from genomic dna obtained from the parents of an infant from the Faroe islands who died in the neonatal period and from two Hispanic sisters who presented with acute neonatal hyperammonemia. Both parents of the first patient were found to be heterozygous for a null mutation in exon 4 (TGG-->TAG, Trp324Ter). Both sisters from the second family were homozygous for a single base deletion in exon 4 (1025delG) causing a frameshift and premature termination of translation. The finding of deleterious mutations in the NAGS gene confirms the genetic origin of NAGS deficiency. This disorder can now be diagnosed by dna testing allowing for carrier detection and prenatal diagnosis.- - - - - - - - - - ranking = 0.42857142857143keywords = deficiency (Clic here for more details about this article) |
5/29. s-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism.We report studies of a Croatian boy, a proven case of human s-adenosylhomocysteine (AdoHcy) hydrolase deficiency. Psychomotor development was slow until his fifth month; thereafter, virtually absent until treatment was started. He had marked hypotonia with elevated serum creatine kinase and transaminases, prolonged prothrombin time and low albumin. Electron microscopy of muscle showed numerous abnormal myelin figures; liver biopsy showed mild hepatitis with sparse rough endoplasmic reticulum. brain MRI at 12.7 months revealed white matter atrophy and abnormally slow myelination. Hypermethioninemia was present in the initial metabolic study at age 8 months, and persisted (up to 784 microM) without tyrosine elevation. plasma total homocysteine was very slightly elevated for an infant to 14.5-15.9 microM. In plasma, s-adenosylmethionine was 30-fold and AdoHcy 150-fold elevated. Activity of AdoHcy hydrolase was approximately equal to 3% of control in liver and was 5-10% of the control values in red blood cells and cultured fibroblasts. We found no evidence of a soluble inhibitor of the enzyme in extracts of the patient's cultured fibroblasts. Additional pretreatment abnormalities in plasma included low concentrations of phosphatidylcholine and choline, with elevations of guanidinoacetate, betaine, dimethylglycine, and cystathionine. Leukocyte dna was hypermethylated. Gene analysis revealed two mutations in exon 4: a maternally derived stop codon, and a paternally derived missense mutation. We discuss reasons for biochemical abnormalities and pathophysiological aspects of AdoHcy hydrolase deficiency.- - - - - - - - - - ranking = 0.85714285714286keywords = deficiency (Clic here for more details about this article) |
6/29. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.Ca(V)1.2, the cardiac L-type calcium channel, is important for excitation and contraction of the heart. Its role in other tissues is unclear. Here we present Timothy syndrome, a novel disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. In every case, Timothy syndrome results from the identical, de novo Ca(V)1.2 missense mutation G406R. Ca(V)1.2 is expressed in all affected tissues. Functional expression reveals that G406R produces maintained inward Ca(2 ) currents by causing nearly complete loss of voltage-dependent channel inactivation. This likely induces intracellular Ca(2 ) overload in multiple cell types. In the heart, prolonged Ca(2 ) current delays cardiomyocyte repolarization and increases risk of arrhythmia, the ultimate cause of death in this disorder. These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2 ) signaling in autism.- - - - - - - - - - ranking = 0.14285714285714keywords = deficiency (Clic here for more details about this article) |
7/29. Leukocyte adhesion deficiency: identification of novel mutations in two Japanese patients with a severe form.Leukocyte adhesion deficiency is a disorder with mutations of the gene for the beta subunit, a component common to three adhesion molecules; LFA-1, Mac-1 and p150,95. The molecular basis of the disorder was studied in two patients with its severe form. In the first patient, the mutant gene expressed an aberrant mRNA, 1.2 kb longer than usual, resulting from a G to A substitution at the splice donor site of a 1.2 kb intron. Several aberrantly spliced messages, arising from splicing at cryptic donor sites, were also identified. The beta subunit proteins deduced from the mRNA sequences lacked half the carboxyl terminal portion. In the second patient, the mutation was a G to A transition at nucleotide 454, which resulted in an Asp128 to Asn substitution of the beta subunit. The 128th Asp residue is located in a region crucial for the association with alpha subunits and strictly conserved among the integrin beta subunits so far analyzed.- - - - - - - - - - ranking = 0.71849531104329keywords = deficiency, alpha (Clic here for more details about this article) |
8/29. Impaired release of tissue plasminogen activator (t-PA) following DDAVP infusion in von Willebrand's disease with low platelet von willebrand factor content.tissue plasminogen activator (t-PA) and von willebrand factor (vWF) are both released by vascular endothelial cells after the infusion of DDAVP. Such release has not been observed in patients with severe von Willebrand's disease (vWD). In the present work we demonstrate that the degree of simultaneous DDAVP-induced release of t-PA and vWF, in patients with vWD, is strictly related to the platelet vWF content. Twelve patients with type I, and three patients with type III vWD were studied. The type I vWD group included three patients with reduced platelet vWF content (platelet-low) and nine patients with normal levels (platelet-normal). In all patients studied the plasma t-PA levels were within the normal range. No significant change in either t-PA or vWF was observed after DDAVP in the patients with undetectable levels of platelet vWF (type III vWD). A mild increase was found in those patients with type I platelet-low, while in type I platelet-normal vWD the response was similar to that observed in normal subjects. The release of the two molecules appeared, therefore, to be linked to platelet vWF content and the rates of increase in both t-PA and vWF were similar in each group of patients studied. Since platelets are regarded as a tissue compartment of vWF our findings seem to suggest that the presence of vWF and its release from endothelial cells is required for a normal concomitant release of t-PA. In contrast, post-DDAVP release of vWF seems to be independent from that of t-PA since it was normal in a patient with congenital deficiency of t-PA release.- - - - - - - - - - ranking = 0.14285714285714keywords = deficiency (Clic here for more details about this article) |
9/29. Inherited deficiency of the ninth component of complement associated with streptococcal infection.A 7 year old boy, who presented with streptococcal infection, was found to have a low serum complement level (CH50). The C9 component was undetectable. His CH50 rose to the normal value and remained normal for at least three weeks, but decreased to one-third of the normal level three months later. family studies were consistent with a familial C9 deficiency, with autosomal co-dominant inheritance.- - - - - - - - - - ranking = 0.71428571428571keywords = deficiency (Clic here for more details about this article) |
10/29. Albright's hereditary osteodystrophy.Albright's hereditary osteodystrophy is a rare inherited metabolic disorder characterized by a typical phenotype. It may be associated with or without resistance to parathyroid hormone (pseudohypoparathyroidism). Both forms may co-exist in the same family. pseudohypoparathyroidism Type 1 and Pseudo-pseudohypoparathyroidism occur as a consequence of reduced erythrocyte membrane coupled with Gs alpha activity. We report here the variable inheritance of hormone resistance in the presence of characteristic phenotype and reduced Gs alpha activity in the same family.- - - - - - - - - - ranking = 0.0084191935151429keywords = alpha (Clic here for more details about this article) |
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