Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type I glycogen storage disease (GSD-I) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney and intestine. Although kidney enlargement occurs in GSD-I, renal disease has not been considered a major problem until recently. In older patients (more than 20 years of age) whose GSD-I disease has been ineffectively treated, virtually all have disturbed renal function, manifested by persistent proteinuria; many also have hypertension, renal stones, altered creatinine clearance or a progressive renal insufficiency. Glomerular hyperfiltration is seen in the early stage of the renal dysfunction and can occur before proteinuria. In younger GSD-I patients, the hyperfiltration is usually the only renal abnormality found; and, in some patients, microalbuminuria develops before clinical proteinuria. The predominant underlying renal pathology is focal segmental glomerulosclerosis. Renal stones and/or nephrocalcinosis are also common findings. Amyloidosis and Fanconi-like syndrome can occur, but rarely. The risk factors for developing the glomerulosclerosis in GSD-I include hyperfiltration, hypertension, hyperlipidemia and hyperuricemia. Dietary therapy with cornstarch and/or nasogastric infusion of glucose, aimed at maintaining normoglycemia, corrects metabolic abnormalities and improves the proximal renal tubular function. Long-term trial will be needed to assess whether the dietary therapy may prevent the evolution or the progression of the renal disease.
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PMID:Type I glycogen storage disease: kidney involvement, pathogenesis and its treatment. 202 44

The effects of high-dose indomethacin (three daily dose, 8.5 mg/kg ip) on pathology and histology, on serum and urine biochemistry, and on various hepatic enzyme activities were studied in rats. Hepatic cytochrome P-450 and aminopyrine N-demethylase were decreased by 52-62%, but glucuronyl transferase fell by only 22%. Hepatic glucose-6-phosphatase, aryl esterase, 6-phosphogluconate dehydrogenase and sulphotransferase remained unchanged, while glucose-6-phosphate dehydrogenase increased by 29%. There were no widespread changes in hepatic and renal pathology or histology, but noteworthy was a mild, focal, centrilobular hepatic response. By contrast, there were severe intestinal lesions: the effects on hepatic enzymes might have been partly a consequence of the intestinal damage. There was a reversible uraemia and significant decreases (20-40% below normal) in both serum albumin and protein, while serum levels of creatinine and aspartate-amino-transferase activity remained constant. A reversible N-acetyl-beta-D-glucoseaminidase (NAG) enzymuria occurred (300% above normal), but no significant proteinuria (less than 300 mg/l). Administration of 16, 16-dimethylprostaglandin F2 alpha(0.5 mg/kg iv) concomitantly with the indomethacin greatly ameliorated the intestinal lesions and prevented the decreases in hepatic drug-metabolizing enzymes. Concomitant 16,16-dimethylprostaglandin F2 alpha did not, however, influence the indomethacin-induced decreases in serum protein, albumin or NAG-enzymuria. It was concluded that indomethacin had a highly selective effect causing a decrease in hepatic cytochrome P-450, which was not accompanied by severe damage to hepatocyte structure.
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PMID:Comparative effects of indomethacin on hepatic enzymes and histology and on serum indices of liver and kidney function in the rat. 393 37

Deficiency of the enzyme glucose-6-phosphatase is the biochemical defect in glycogen storage disease type I (GSD I). Normally this enzyme is present in the liver, intestine and kidneys. The lack of the enzyme in the kidney makes it obvious that glycogen storage will not be restricted to the liver but that also the kidneys will be involved, possibly resulting in renal damage. Glycogen storage in the kidney is most outspoken present in the proximal tubular cells. In case of insufficient metabolic control, a Fanconi-like syndrome can develop, disappearing with improved therapy. Although renal disease has not been considered a problem in GSD I, recent findings indicate that especially in adult patients chronic renal disease is a common complication. In the past gout nephropathy and renal stones were the complications mentioned. Recently it appears that in a considerable number of patients after a period of 'silent' hyperfiltration, renal damage develops with proteinuria, hypertension and renal dysfunction later on. In biopsies of such patients focal glomerulosclerosis is found.
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PMID:Renal complications in glycogen storage disease type I. 831 28

Glycogen storage disease type Ia (GSDIa) is an inherited disorder of glucose metabolism, due to the selective deficiency of the hepatic enzyme glucose-6-phosphatase. Clinical manifestations include severe hypoglycaemia three to four hours post-prandially, increased production of lactic acid, triglycerides and uric acid, hepatic glycogen storage disease with development of multiple adenomas and kidney disease with proteinuria. Liver transplantation is frequently performed in order to achieve metabolic control and when malignant transformation of adenomas is suspected. Long term outcome following transplantation is good, but immunosuppressive therapy can worsen the progression of associated kidney disease. Hepatocyte transplantation could be considered as a less invasive procedure in such patients. Our experience with hepatocyte transplantation in a 47 year-old woman affected by glycogen storage disease type Ia and suffering of severe fasting hypoglycaemia indicates that the procedure can partially correct some metabolic abnormalities and improve the quality of life in this disease. However, the metabolic improvement was reduced and finally abolished during long term follow-up, probably due to rejection or to senescence of transplanted cells. Moreover, the portal and pulmonary hypertension associated with the disease need to be evaluated for their possible influence on haemodynamic changes associated with cell infusion. Finally, hepatic adenomas need careful monitoring because of the possible risk of malignant transformation.
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PMID:Liver and liver cell transplantation for glycogen storage disease type IA. 1643 6

Type Iota(a) glycogen storage disease (GSD Iota(a)) is caused by the deficiency of glucose-6-phosphatase activity, which results in metabolic disorder and organ failure, including renal failure. GSD Iota(a) patients are generally diagnosed at a median age of 6 months. However, we report a 20-year-old Japanese female with newly diagnosed GSD Iota(a) . The renal disorder of GSD Iota(a) is considered to be produced by glomerular hyperfiltration, TGF-beta expression which is induced by renin-angiotensin-aldosterone system (RAS) and uric acid, and the increase in both small dense LDL and modified LDL which is characteristic of GSD Iota(a) as well as hypertriglyceridemia. With the administration of intensive therapies, including angiotensin type 1-receptor blocker and some lipid lowering drugs, along with traditional dietary therapy, daily proteinuria of the patient improved from 2.1 g to 0.78 g. Although the patients of GSD Iota(a) should receive an early and accurate diagnosis and effective therapies before the age of 1 year, the combination of traditional dietary therapies and intensive therapies may have therapeutic potential for the complications of adult patients. In this report, we describe the management of renal disease and the characteristic features of this metabolic disorder.
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PMID:Early diagnosis and treatment may prevent the development of complications in an adult patient with glycogen storage disease type Ia. 2072 Mar 60

Glycogen storage disease type Ia (GSD Ia) leads to disturbed glycogenolysis and gluconeogenesis due to a deficiency in the enzyme glucose-6-phosphatase. A patient with GSD Ia showed hypoglycemia and proteinuria without dietary management since early pregnancy. The patient's condition was complicated by hypertension with increase in proteinuria at 22 weeks of gestation. In spite of administration of antihypertensive drugs and dietary management, the disease became more severe with deterioration in the fetal status and inhibition of fetal growth. Thus, a cesarean section was performed at 26 weeks of gestation. The delivered male infant weighing 412 g died at 2 days after birth. The patient's blood pressure had normalized within 3 months after delivery, while proteinuria persisted.
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PMID:Glycogen storage disease type Ia (GSD Ia) during pregnancy: report of a case complicated by fetal growth restriction and preeclampsia. 2105 47

Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg/dl) was prevented for >6 months by the dsAAV2/7, dsAAV2/8, and dsAAV2/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2/7 and dsAAV2/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2/9 vector. Hepatorenal correction in G6pase (-/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.
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PMID:Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector. 2173 Sep 73