MedGen

C3 glomerulopathy is a group of related conditions that cause the kidneys to malfunction. The major features of C3 glomerulopathy include high levels of protein in the urine (proteinuria), blood in the urine (hematuria), reduced amounts of urine, low levels of protein in the blood, and swelling in many areas of the body. Affected individuals may have particularly low levels of a protein called complement component 3 (or C3) in the blood.

The kidney problems associated with C3 glomerulopathy tend to worsen over time. About half of affected individuals develop end-stage renal disease (ESRD) within 10 years after their diagnosis. ESRD is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.

Researchers have identified two major forms of C3 glomerulopathy: dense deposit disease and C3 glomerulonephritis. Although the two disorders cause similar kidney problems, the features of dense deposit disease tend to appear earlier than those of C3 glomerulonephritis, usually in adolescence. However, the signs and symptoms of either disease may not begin until adulthood.

One of the two forms of C3 glomerulopathy, dense deposit disease, can also be associated with other conditions unrelated to kidney function. For example, people with dense deposit disease may have acquired partial lipodystrophy, a condition characterized by a lack of fatty (adipose) tissue under the skin in the upper part of the body. Additionally, some people with dense deposit disease develop a buildup of yellowish deposits called drusen in the light-sensitive tissue at the back of the eye (the retina). These deposits usually appear in childhood or adolescence and can cause vision problems later in life. [from MedlinePlus Genetics]

Proton pump inhibitors (PPIs) inhibit the final pathway of acid production, which leads to inhibition of gastric acid secretion. PPIs are widely used in the treatment and prevention of many conditions including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, H. pylori infection, and pathological hypersecretory conditions. The first-generation inhibitors omeprazole, lansoprazole and pantoprazole are extensively metabolized by the cytochrome P450 isoform CYP2C19 and to a lesser extent by CYP3A4. The second-generation PPI dexlansoprazole appears to share a similar metabolic pathway to lansoprazole. CYP2C19 genotypes have been linked to PPI exposure and in turn to PPI efficacy and adverse effects. CYP2C19 intermediate (IMs) and poor metabolizers (PMs) have been associated with decreased clearance and increased plasma concentrations of the first-generation PPIs, which leads to increased treatment success compared to CYP2C19 normal metabolizers (NMs). However, higher exposure and long-term use of PPIs have also been associated with adverse effects. CYP2C19 ultrarapid (UMs) and rapid metabolizers (RMs) have shown increased metabolism compared to NMs, which may increase the risk of treatment failure. Guidelines regarding the use of pharmacogenomic tests in dosing for PPIs have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. The CPIC guideline provides specific therapeutic recommendations for four PPIs (omeprazole, lansoprazole, pantoprazole, and dexlansoprazole) based on CYP2C19 genotype. [from PharmGKB]

Proton pump inhibitors (PPIs) inhibit the final pathway of acid production, which leads to inhibition of gastric acid secretion. PPIs are widely used in the treatment and prevention of many conditions including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, H. pylori infection, and pathological hypersecretory conditions. The first-generation inhibitors omeprazole, lansoprazole and pantoprazole are extensively metabolized by the cytochrome P450 isoform CYP2C19 and to a lesser extent by CYP3A4. The second-generation PPI dexlansoprazole appears to share a similar metabolic pathway to lansoprazole. CYP2C19 genotypes have been linked to PPI exposure and in turn to PPI efficacy and adverse effects. CYP2C19 intermediate (IMs) and poor metabolizers (PMs) have been associated with decreased clearance and increased plasma concentrations of the first-generation PPIs, which leads to increased treatment success compared to CYP2C19 normal metabolizers (NMs). However, higher exposure and long-term use of PPIs have also been associated with adverse effects. CYP2C19 ultrarapid (UMs) and rapid metabolizers (RMs) have shown increased metabolism compared to NMs, which may increase the risk of treatment failure. Guidelines regarding the use of pharmacogenomic tests in dosing for PPIs have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. The CPIC guideline provides specific therapeutic recommendations for four PPIs (omeprazole, lansoprazole, pantoprazole, and dexlansoprazole) based on CYP2C19 genotype. [from PharmGKB]

VACTERL is an acronym for vertebral anomalies (similar to those of spondylocostal dysplasia), anal atresia, cardiac malformations, tracheoesophageal fistula, renal anomalies (urethral atresia with hydronephrosis), and limb anomalies (hexadactyly, humeral hypoplasia, radial aplasia, and proximally placed thumb; see 192350). Some patients may have hydrocephalus, which is referred to as VACTERL-H (Briard et al., 1984). [from OMIM]

Proton pump inhibitors (PPIs) inhibit the final pathway of acid production, which leads to inhibition of gastric acid secretion. PPIs are widely used in the treatment and prevention of many conditions including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, H. pylori infection, and pathological hypersecretory conditions. The first-generation inhibitors omeprazole, lansoprazole and pantoprazole are extensively metabolized by the cytochrome P450 isoform CYP2C19 and to a lesser extent by CYP3A4. The second-generation PPI dexlansoprazole appears to share a similar metabolic pathway to lansoprazole. CYP2C19 genotypes have been linked to PPI exposure and in turn to PPI efficacy and adverse effects. CYP2C19 intermediate (IMs) and poor metabolizers (PMs) have been associated with decreased clearance and increased plasma concentrations of the first-generation PPIs, which leads to increased treatment success compared to CYP2C19 normal metabolizers (NMs). However, higher exposure and long-term use of PPIs have also been associated with adverse effects. CYP2C19 ultrarapid (UMs) and rapid metabolizers (RMs) have shown increased metabolism compared to NMs, which may increase the risk of treatment failure. Guidelines regarding the use of pharmacogenomic tests in dosing for PPIs have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. The CPIC guideline provides specific therapeutic recommendations for four PPIs (omeprazole, lansoprazole, pantoprazole, and dexlansoprazole) based on CYP2C19 genotype. [from PharmGKB]

Proton pump inhibitors (PPIs) inhibit the final pathway of acid production, which leads to inhibition of gastric acid secretion. PPIs are widely used in the treatment and prevention of many conditions including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, H. pylori infection, and pathological hypersecretory conditions. The first-generation inhibitors omeprazole, lansoprazole and pantoprazole are extensively metabolized by the cytochrome P450 isoform CYP2C19 and to a lesser extent by CYP3A4. The second-generation PPI dexlansoprazole appears to share a similar metabolic pathway to lansoprazole. CYP2C19 genotypes have been linked to PPI exposure and in turn to PPI efficacy and adverse effects. CYP2C19 intermediate (IMs) and poor metabolizers (PMs) have been associated with decreased clearance and increased plasma concentrations of the first-generation PPIs, which leads to increased treatment success compared to CYP2C19 normal metabolizers (NMs). However, higher exposure and long-term use of PPIs have also been associated with adverse effects. CYP2C19 ultrarapid (UMs) and rapid metabolizers (RMs) have shown increased metabolism compared to NMs, which may increase the risk of treatment failure. Guidelines regarding the use of pharmacogenomic tests in dosing for PPIs have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. The CPIC guideline provides specific therapeutic recommendations for four PPIs (omeprazole, lansoprazole, pantoprazole, and dexlansoprazole) based on CYP2C19 genotype. [from PharmGKB]