Primary Hyperoxaluria (Total 195326 Papers Found)

Massive myocardial calcification is a very rare finding usually associated with previous myocardial infarction, ventricular aneurysms, myocarditis, endomyocardial fibrosis, tuberculosis and systemic metabolic disease such as sarcoidosis and primary hyperoxaluria. Rarely, it can be associated with idiopathic mitral annular calcification or rheumatic heart disease. We report an unusual case of massive myocardial calcification without other predisposing factors and with documented disease progressi ...
Primary hyperoxaluria is a genetic disorder in glyoxylate metabolism that leads to systemic overproduction of oxalate. Functional deficiency of alanine-glyoxylate aminotransferase in this disease leads to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and kidney failure. We present a young woman with end-stage renal disease who received a kidney allograft and experienced early graft failure presumed to be an acute rejection. There was no improvement in kidney function, and she w ...
We analyzed the records of 3 patients transplanted for end-stage renal failure due to primary hyperoxaluria and evaluated on repeat biopsies the role played by oxalate deposits in the constitution of renal failure after isolated kidney graft, or combined liver and kidney transplantation. Early failure of the renal graft is frequent and often interpreted as the consequence of recurrence because of the presence of oxalate deposits on the graft biopsy. In fact, the decrease in oxalate deposits obse ...
Most organ transplantations have clear-cut indications, and the results have improved substantially over the years. Long-term results in children are today comparable to those in adults. The most common indications for kidney transplantation (KT) are obstructive uropathies and malformations of the urinary tract followed by glomerulonephritis and congenital diseases. Fiveto 10-yr survivals are excellent, and the timing of renal transplantation is well defined. Heart transplantation is performed i ...
Immunoblotting of human liver sonicates, after SDS-polyacrylamide gel electrophoresis, demonstrated the presence of a 40 kDa protein, corresponding to the subunit of alanine:glyoxylate aminotransferase, in six controls and three patients with primary hyperoxaluria type 1 (peroxisomal alanine:glyoxylate aminotransferase deficiency). This immunoreactive 40 kDa protein was absent in a further nine patients. Subcellular fractionation of patients' livers showed that the 40 kDa protein, when present, ...
Dear Editor, Bone marrow (BM) oxalosis is a type of systemic oxalosis wherein oxalate is deposited in BM. It is characterized by cytopenias, leukoerythroblastosis, and hepatosplenomegaly [1] as well as BM findings of calcium oxalate crystals that are birefringent under polarized microscopy and granulomatous structures [2]. Hyperoxaluria (excessive urinary excretion of oxalate) can develop into systemic oxalosis when oxalate is deposited in organs [3]. Hyperoxaluria is classified as primary or se ...
ed with poor feeding, respiratory distress and decreased urine output. He was noted to be in the 1st percentile for weight, and 60th percentile for height. At admission he was hypertensive with systolic blood pressures ranging from 107-124 mmHg and diastolic pressures of 6672 mmHg. Physical exam was remarkable for fussiness and decreased musculoskeletal tone for age. Labs demonstrated hemoglobin 4.5 g/dL, sodium 121 mmol/L, potassium 7.5 mmol/L, blood urea nitrogen 239 mg/dL, serum creatinine of ...
Recent population studies have found symptomatic kidney stone formers to be at increased risk for chronic kidney disease (CKD). Although kidney stones are not commonly identified as the primary cause of ESRD, they still may be important contributing factors. Paradoxically, CKD can be protective against forming kidney stones because of the substantial reduction in urine calcium excretion. Among stone formers, those with rare hereditary diseases (cystinuria, primary hyperoxaluria, Dent disease, an ...
Primary hyperoxaluria type 1 (PH1) is a rare autosomal-recessive disorder, caused by a deficiency of the liver-specific intermediary-metabolic enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in increased synthesis and excretion of the metabolic end-product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. Numerous mutations and polymorphisms have been identified in the gene (AGXT) that encodes AGT, some of which interact synergistic ...
Recent advances in RNA interference (RNAi) delivery and chemistry have resulted in the development of more than 20 RNAi-based therapeutics, several of which are now in Phase III trials. The most advanced clinical trials have utilized modifications such as lipid nanoparticles and conjugation to N-acetyl galactosamine to treat liver specific diseases. Recent reports have suggested that reducing endogenous oxalate synthesis by RNAi may be a safe and effective therapy for patients with the rare dise ...
OBJECTIVE Hyperglycolic hyperoxaluria is an important biochemical diagnostic hallmark for primary hyperoxaluria type 1 (PH1). Biochemical work-up on urinary specimens becomes impossible after the development end-stage renal failure and anuria. We studied the diagnostic value of determining glycolic acid content in peritoneal dialysate effluent in PH1. PATIENTS AND METHODS We performed a comparative study on an anuric continuous ambulatory peritoneal dialysis (CAPD) patient whose PH1 was confir ...
Many inborn errors of amino acids metabolism are caused by single point mutations affecting the ability of proteins to fold properly (i.e., protein homeostasis), thus leading to enzyme loss-of-function. Mutations may affect protein homeostasis by altering intrinsic physical properties of the polypeptide (folding thermodynamics, and rates of folding/unfolding/misfolding) as well as the interaction of partially folded states with elements of the protein homeostasis network (such as molecular chape ...
The primary hyperoxalurias type 1 (PH1) and type 2 (PH2) are autosomal recessive calcium oxalate kidney stone diseases caused by deficiencies of the metabolic enzymes alanine:glyoxylate aminotransferase (AGT) and glyoxylate/hydroxypyruvate reductase (GR/HPR), respectively. Over 50 mutations have been identified in the AGXT gene (encoding AGT) in PH1, associated with a wide variety of effects on AGT, including loss of catalytic activity, aggregation, accelerated degradation, and peroxisome-to-mit ...
Primary hyperoxaluria type I (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine : glyoxylate aminotransferase (AGT) which is deficient or mistargeted to mitochondria. PH1 shows considerable phenotypic and genotypic heterogeneity. The incidence and severity of PH1 varies in different geographic regions. DNA samples of the affected members from two unrelated Tunisian families were tested by amplifying and sequencing ...
Primary hyperoxaluria type 1 (PH1) is a genetic disorder in which there is a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGXT). In the absence of enzyme activity, glyoxylate is converted to oxalate, which forms insoluble calcium salts that cause nephrolithiasis, nephrocalcinosis, and ultimately renal failure. As kidney function declines and glomerular filtration rate decreases, systemic oxalosis develops with the accumulation of calcium oxalate in ext ...
  • G. N. Wilson,
  • Biochemical medicine and metabolic biology
  • 1991
Progress relevant to human peroxisomal disorders over the past 3 years includes improved biochemical delineation of disease phenotypes and new insights into peroxisomal structure and biogenesis. Immunoblotting studies using antibodies to peroxisomal beta-oxidation enzymes have defined mutations affecting each step of the pathway, some with clinical phenotypes as severe as disorders with global peroxisome deficiency. The latter disorders, typified by Zellweger syndrome, often lack matrix proteins ...
Mutations in the alanine-glyoxylate amino transferase gene (AGXT) are responsible for primary hyperoxaluria type I, a rare disease characterized by excessive hepatic oxalate production that leads to renal failure. We generated a null mutant mouse by targeted mutagenesis of the homologous gene, Agxt, in embryonic stem cells. Mutant mice developed normally, and they exhibited hyperoxaluria and crystalluria. Approximately half of the male mice in mixed genetic background developed calcium oxalate u ...
Recurrence of the original disease in the transplanted kidney is observed in 5.6%-9.3% of the patients. However, the clinical significance of recurrence is often minor. Diagnosis is easy in diseases with specific renal lesions, e.g., in dense deposit disease and IgA-nephropathy, but may be difficult if such a marker is missing. Recurrence is of special clinical importance in the following conditions: Membranoproliferative GN type I (in 33%, often severe) and type II (= dense deposit disease, rec ...
The human hereditary disease primary hyperoxaluria type 1 is caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). In this study, the crystallization and preliminary crystallographic analysis of C-terminal His-tagged human AGT expressed in Escherichia coli is reported. At least two crystal forms were obtained using similar conditions for three different polymorphic variants, namely AGT, AGT[P11L] and AGT[P11L, I340M]. Complete data have been c ...
Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, t ...
INTRODUCTION Because of the shortage of organs available for transplantation, living related sequential transplantation with the use of liver and a kidney from the same donor has emerged as a reasonable therapeutic alternative. However, there is insufficient literature about the complications that living donors experience after simultaneous kidney and liver transplantations. METHODS From December 2001 to October 2009, 5 living donors provided simultaneous donation of livers and kidneys and 1 l ...
Primary hyperoxaluria type I (PH I) is a rare recessive autosomal disorder characterized by systemic calcium oxalate depositions, that results in renal failure and systemic oxalosis. We report a 38-year-old male with cardiac oxalosis, a severe complication of PHI, presenting with an infiltrative cardiomyopathy, secondary heart failure and severe mitral regurgitation, necessitating surgical repair to allow combined liver-kidney transplantation. We discuss pathogenesis, diagnostics and therapy of ...
Hypericum polyanthemum, H. caprifoliatum and H. myrianthum, are vegetal species native to southern Brazil and demonstrated antinociceptive and antidepressant-like effects. These species have a strong tendency to accumulate phenolic compounds with the phloroglucinol substitution pattern, such as benzopyrans (HP1, HP2, HP3) and dimeric phloroglucinol derivatives (uliginosin B, hyperbrasilol B, japonicin A). Pre-clinical studies suggest that dimeric phloroglucinols and benzopyrans might constitute ...
We describe three novel deletions in the human AGT gene in three patients with primary hyperoxaluria type 1, an autosomal recessive disease resulting from a deficiency of the liver peroxisomal enzyme, alanine glyoxylate aminotransferase (AGT; EC 2.6.1.44). A deletion of 4 nucleotides in the exon 6/intron 6 splice junction (679-IVS6+2delAAgt) is expected to cause missplicing. It would also code for a K227E missense alteration in any mRNA successfully spliced. A 2-bp deletion in exon 11 (1125-1126 ...
Of 166 paediatric liver transplant recipients, 17(10.2%) had transplant for a metabolic disorder. Four had α-1-antitrypsin deficiency (mean age 9.1 y) , 5 Wilson's disease (mean age 11.2 y), 2 tyrosinemia (1y & 4y) , 1 type IV glycogenosis (1 y). Five had no liver insufficiency: three Crigler-Najjar syndromes (2.2, 3.5 & 7.5 y), 1 type I glycogenosis (7 y), 1 primary hyperoxaluria (10y, liver-kidney transplantation). Type IV glycogenosis patient died subsequently from related cardiac failure. T ...
Few data have been published on the course of oxalosis cardiomyopathy after combined liver and kidney transplantation in hyperoxaluria patients with myocardial involvement. We report the case of a primary hyperoxaluria type 1 patient with renal failure who developed end-stage cardiomyopathy. Left venticulography showed severe diffuse hypokinesia and left ventricular ejection fraction was calculated at 12%. Endomyocardial biopsy demonstrated platelike calcium oxalate crystals within the myocardiu ...
Semantic Scholar extracted view of "The conversion of [1-13C]glycine and [2-13C]glycine to [13C]oxalate in primary hyperoxaluria: evidence for the existence of more than one metabolic pathway from glycine to oxalate in man." by Brian Dean et al. ...
BACKGROUND Angiotensinogen (AGT) M235T and angiotensin-converting enzyme (ACE) Insertion/Deletion polymorphisms have been reported to be significantly associated with ischemic stroke. However, the results have been inconsistent. Therefore, we performed a comprehensive meta-analysis to evaluate the role of the AGT M235T and ACE I/D polymorphisms as risk factors for ischemic stroke in Han Chinese population. METHODS We performed a comprehensive search in MEDLINE (PubMed), the China National Know ...
BACKGROUND In primary hyperoxaluria type I (PH 1), hepatic overproduction of oxalate leads to its deposition in various organ systems including bone (oxalosis). To evaluate skeletal status non-invasively in PH 1 we measured bone mineral density (BMD). METHODS Peripheral quantitative computed tomography of the distal radius was performed in 10 children with PH 1 (mean chronological age 9+/-3.1, mean skeletal age 8.3+/-3.0 years): seven were on conservative treatment (CT) including one patient a ...
Primary hyperoxaluria is an uncommon, inherited metabolic disorder due to hepatic enzyme deficiencies with consequent hepatic oxalate overproduction and attendant systemic complications. The diagnosis is established on a combination of clinical parameters, elevated urinary excretion of oxalate and glycolate and determination of alanine glyoxylate aminotransferase in the liver tissue. We describe a 45-year-old female with end-stage renal disease secondary to nephrolithiasis, who presented with a ...