Search results for "Cystinuria"

ABNORMALLY HIGH THROMBOXANE BIOSYNTHESIS IN HOMOZYGOUS HOMOCYSTINURIA. EVIDENCE FOR PLATELET INVOLVEMENT AND PROBUCOL-SENSITIVE MECHANISM.

1993

Homocystinuria due to homozygous cystathionine beta-synthase deficiency is an inborn error of metabolism characterized by a high incidence of thrombosis and premature atherosclerosis. We evaluated TXA2 biosynthesis in vivo and several in vitro tests of platelet function in 11 homocystinuric patients and 12 healthy controls. In vitro, patients' platelet aggregation was within control values as were TXB2 formation, fibrinogen binding, and ATP secretion in response to thrombin. In contrast, the urinary excretion of 11-dehydro-TXB2, a major enzymatic derivative of TXA2, was > 2 SD of controls in all patients (1,724 +/- 828 pg/mg creatinine, mean +/- SD, in patients vs. 345 +/- 136 in controls, …

Cystinuria subtype and nephrolithiasis

1999

PATHOPHYSIOLOGY AND CLINICAL ASPECTS OF URINARY LITHIASIS

2007

Urine is a complex balanced solution containing dissociated and non-dissociated solutes. Any variation in urine saturation grade (number of crystals dissolved in a volume of urine), urinary pH and the concentration of crystallization inhibitors can break the normal existing balance and lead to urolithiasis. In the present article we analyze the principal mechanisms (absorptive, renal, resorptive) of hypercalciuria. It will be also shown how heredity directly influences the clinical aspects of cystine, xanthine and oxalate lithiasis and how diet, in association with metabolic disorders, interferes in uric acid and oxalate stone formation. Finally, we report on the roles of urinary tract malf…

Investigation on a MMACHC mutant from cblC disease: The c.394C>T variant

2022

The cblC disease is an inborn disorder of the vitamin B12 (cobalamin, Cbl) metabolism characterized by methylmalonic aciduria and homocystinuria. The clinical consequences of this disease are devastating and, even when early treated with current therapies, the affected children manifest symptoms involving vision, growth, and learning. The illness is caused by mutations in the gene codifying for MMACHC, a 282aa protein that transports and transforms the different Cbl forms. Here we present data on the structural properties of the truncated protein p.R132X resulting from the c.394C > T mutation that, along with c.271dupA and c.331C > T, is among the most common mutations in cblC. Althou…

Differential cystine and dibasic amino acid handling after loss of function of the amino acid transporter b0,+ AT (Slc7a9) in mice

2013

Cystinuria is an autosomal recessive disease caused by mutations in SLC3A1 ( rBAT) and SLC7A9 ( b 0,+ AT). Gene targeting of the catalytic subunit ( Slc7a9) in mice leads to excessive excretion of cystine, lysine, arginine, and ornithine. Here, we studied this non-type I cystinuria mouse model using gene expression analysis, Western blotting, clearance, and brush-border membrane vesicle (BBMV) uptake experiments to further characterize the renal and intestinal consequences of losing Slc7a9 function. The electrogenic and BBMV flux studies in the intestine suggested that arginine and ornithine are transported via other routes apart from system b0,+. No remarkable gene expression changes were…

Identification of novel SLC3A1 gene mutations in Spanish cystinuria families and association with clinical phenotypes

2004

Cystinuria is an inherited metabolic disease characterized by an abnormal urinary excretion of cystine and dibasic amino acids, leading to kidney stone formation. Incidence of cystinuria in the Mediterranean Spanish population is one of the highest in the world. In view of the low prevalence of previously reported mutations in the SLC3A1 gene, analyses to identify novel variants were carried out on 20 cystinuria families. Additionally, we investigated the possible association between these molecular variants and clinical phenotypes. Genomic DNA from 48 cystinuria patients, 44 healthy relatives and 81 unrelated controls from the East Mediterranean coast of Spain was screened by conformation …

Association between M467T and 114 C--A variants within the SLC3A1 gene and some phenotypical traits in cystinuria patients from Spain.

2000

Cystinuria is an inherited metabolic disease characterized by an abnormal urinary excretion of cystine and dibasic amino acids. Formation of renal calculi, recurrent infections and renal failure are the main complications of this disease. The SLC3A1 gene, which codes for a dibasic amino acid transporter protein, is involved in the pathogenesis of cystinuria. We investigated the possible association between molecular variants (M467T, E483X, T216 M and 114 C--A) within the SLC3A1 gene and some phenotypical traits in a Spanish area. The study population consisted of 45 cystinuria patients, 42 cystinuria relatives and 81 healthy control subjects. Only the M467T mutation was found in chromosomes…