Abstract:
INTRODUCTION:Alkaptonuria (AKU) is a rare inherited disorder of tyrosine metabolism resulting in an accumulation of homogentisic acid oxidation products in the joints and cardiovascular system. Aortic distensibility may be a non-invasive indicator of cardiovascular complications. Descending thoracic aortic distensibility in alkaptonuria has not been studied. METHODS:Patients diagnosed with alkaptonuria underwent Magnetic Resonance Imaging (MRI) and gated non-contrast and contrast-enhanced cardiovascular computed tomography. Using MRI cine images, aortic distensibility of the descending thoracic aorta was determined. RESULTS:Seventy-six patients with alkaptonuria were imaged. When compared to literature normal values, aortic distensibility in AKU was impaired (5.2 vs 6.2 × 10-3, p < .001). Aortic distensibility was inversely related to age (r = -0.6, p = .0001). Hypertensive patients with alkaptonuria had impaired distensibility compared to normotensive patients with alkaptonuria (4.6 vs 5.6 × 10-3, p = .03), and hyperlipidemic patients with alkaptonuria had impaired distensibility compared to non-hyperlipidemic patients with alkaptonuria (4.1 vs 6.0 × 10-3, p = .001). Male hypertensive patients with alkaptonuria had greater distensibility than their female counterparts (5.3 vs 2.9 × 10-3, p = .02). Similarly, male hyperlipidemic patients with alkaptonuria had greater distensibility than their female counterparts (4.8 vs 2.5 × 10-3, p < .01). Of patients with alkaptonuria, those with a coronary artery calcium (CAC) score greater than 100 had more impaired distensibility than those with a CAC score less than 100 (3.5 vs 5.1 × 10-3, p = .01) and those with aortic calcium score greater than 100 had impaired distensibility compared to those with an aortic calcium score less than 100 (3.2 vs 4.9 × 10-3, p = .02). Univariate analysis revealed age, aortic calcification, and hyperlipidemia to be significant factors of distensibility, and multiple regression analysis showed age as the only significant risk factor of distensibility. CONCLUSIONS:Patients with alkaptonuria have impaired aortic distensibility, which is likely an early marker for reduced cardiovascular health. Variables such as age, hypertension, hyperlipidemia, and aortic and coronary calcification were associated with impaired distensibility.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Thimmapuram R,Bandettini WP,Shanbhag SM,Yu JH,O'Brien KJ,Gahl WA,Introne WJ,Chen MYdoi
10.1016/j.ymgme.2020.05.006subject
Has Abstractpub_date
2020-08-01 00:00:00pages
289-296issue
4eissn
1096-7192issn
1096-7206pii
S1096-7192(20)30120-7journal_volume
130pub_type
杂志文章abstract:OBJECTIVE:To better delineate the natural history of patients with methylmalonic aciduria (MMA). STUDY DESIGN:Thirty patients with vitamin-B12-unresponsive MMA (25 aged 1.5 to 22.0 years (y) at the end of the study and 5 who died during a metabolic crisis) were managed following standardized guidelines and studied ret...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2009.03.006
更新日期:2009-07-01 00:00:00
abstract::To elucidate the basis of mucopolysaccharidosis type VI (MPS VI) from the point of view of enzyme structure, we built structural models of mutant N-acetylgalactosamine-4-sulfatase (4S) resulting from 34 missense mutations (17 severe and 17 attenuated), and analyzed the influence of each amino acid replacement on the s...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.11.017
更新日期:2008-04-01 00:00:00
abstract::Niemann-Pick type C1 (NPC1) is a rare neurodegenerative disease. In NPC1 mouse cerebella, the antibacterial enzyme, lysozyme (Lyz2), is significantly increased in multiple cell types. Due to its possible role in toxic fibril deposition, we confirmed Lyz2 overexpression in culture in different control and NPC1 cell typ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2020.10.009
更新日期:2020-11-01 00:00:00
abstract::Pyruvate dehydrogenase complex (PDC) deficiency is one of the major recognized causes of congenital lactic acidosis. The most common form is due to PDHA 1 gene (Xp22.12) defects. Here, we report the case of a Polynesian girl presenting with delayed neurological development, cortical atrophy, and posterior corpus callo...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2005.08.009
更新日期:2005-12-01 00:00:00
abstract::X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder characterized by the accumulation of saturated and mono-unsaturated very long-chain fatty acids (VLCFA) and reduced peroxisomal VLCFA beta-oxidation activity. In this study, we investigated the role of VLCFA biosynthesis in X-ALD fibrobl...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2004.09.015
更新日期:2005-02-01 00:00:00
abstract::In mammals, the conversion of alpha-aminoadipate to alpha-ketoadipate by alpha-aminoadipate aminotransferase (AADAT) is an intermediate step in lysine degradation. A gene encoding for alpha-aminoadipate aminotransferase and kynurenine aminotransferase activities had been previously identified in the rat (KAT/AadAT). W...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/s1096-7192(02)00037-9
更新日期:2002-07-01 00:00:00
abstract::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 junc...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2001.3222
更新日期:2001-11-01 00:00:00
abstract::Dyggve-Melchior-Clausen (DMC) is a rare autosomal-recessive disorder characterized by the association of a progressive spondylo-epi-metaphyseal dysplasia and mental retardation ranging from mild to severe. Electron microscopy studies of both DMC chondrocytes and fibroblasts reveal an enlarged endoplasmic reticulum net...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2004.08.012
更新日期:2004-09-01 00:00:00
abstract::Isolated methylmalonic aciduria (MMA) results either from a defect in the mitochondrial enzyme methylmalonylCoA mutase (MCM), or in the intracellular conversion of vitamin B12 (cobalamin) into its active coenzyme adenosylcobalamin (AdoCbl). Mutations in the MMAB gene affect the function of the enzyme ATP:cob(I)alamin ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2013.04.020
更新日期:2013-09-01 00:00:00
abstract::An approach to treating Gaucher disease is substrate inhibition therapy which seeks to abate the aberrant lysosomal accumulation of glucosylceramide. We have identified a novel inhibitor of glucosylceramide synthase (Genz-112638) and assessed its activity in a murine model of Gaucher disease (D409V/null). Biochemical ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.04.001
更新日期:2007-07-01 00:00:00
abstract::The oral contraceptive pill is associated with a modest increase in the risk of early-onset breast cancer in the general population, but it is possible that the risk is higher in certain subgroups of women. The relative risk of breast cancer associated with oral contraceptive use has been reported to be higher for Afr...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2000.3130
更新日期:2001-02-01 00:00:00
abstract::We determined the ability of self-complementary adeno-associated virus (scAAV) vectors to deliver and express the pyruvate dehydrogenase E1alpha subunit gene (PDHA1) in primary cultures of skin fibroblasts from 3 patients with defined mutations in PHDA1 and 3 healthy subjects. Cells were transduced with scAAV vectors ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.10.131
更新日期:2008-04-01 00:00:00
abstract::BH(4) administration results in the reduction of blood phenylalanine level in patients with tetrahydrobiopterin (BH(4))-responsive phenylalanine hydroxylase (PAH) deficiency. The mechanism underlying BH(4) response remains unknown. Here, we studied the effects of BH(4) and phenylalanine on in vivo PAH activity of norm...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.07.013
更新日期:2007-12-01 00:00:00
abstract::Isovaleric acidemia (IVA), a rare recessive autosomal disorder, is caused by isovaleryl-CoA dehydrogenase (IVD) deficiency. IVA may present with symptoms during the acute stage of severe metabolic acidosis, ketosis, vomiting, and altered mental status. With the help of newborn screening (NBS) by tandem mass spectromet...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2006.08.011
更新日期:2007-02-01 00:00:00
abstract::We analyzed constitutional and tumor DNA from 27 MEN1 kindreds not known to be related to each other. Disease allele haplotypes were constructed for each pedigree based on shared alleles from two or more affected members and from determination of allelic loss patterns in their tumors. Analysis of disease allele haplot...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1997.2649
更新日期:1998-02-01 00:00:00
abstract::Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy. Other tissues such as liver, brain, heart, and skin remain unaffected throughout the patients' life. In order to eluci...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/s1096-7192(03)00063-5
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Propionic acidemia (PA) is an organic aciduria caused by inherited deficiency of propionyl-CoA carboxylase. Left ventricular dysfunction and QT prolongation may lead to life-threatening complications. Systematic analyses of cardiac phenotypes, in particular effects of specific cardiac therapies, are scarce. ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2020.02.004
更新日期:2020-05-01 00:00:00
abstract::Tandem mass spectrometry (MS/MS) has been introduced in several newborn screening programs for the detection of a large number of inborn errors of metabolism, including fatty acid oxidation disorders (FAOD). Early identification and treatment of FAOD have the potential to improve outcome and may be life-saving in some...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2001.3282
更新日期:2002-02-01 00:00:00
abstract::The mucopolysaccharidoses (MPS) result from attenuation or loss of enzyme activities required for lysosomal degradation of the glycosaminoglycans, hyaluronan, heparan sulfate, chondroitin/dermatan sulfate, and keratan sulfate. This review provides a summary of glycan biomarkers that have been used to characterize anim...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2013.07.016
更新日期:2014-02-01 00:00:00
abstract::We report a transient drop in plasma Hcy and Cys following a single oral dose of PteGlu. The thiol change was concomitant with both the peak plasma 5CH3H4PteGlu1 level (by HPLC) and the maximum plasma Lactobacillus casei activity which reflects absorption of unmodified PteGlu. The significant reciprocal association of...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1999.2813
更新日期:1999-05-01 00:00:00
abstract::Mucolipidosis type II is an autosomal recessive lysosomal storage disease caused by N-acetylglucosamine-1-phosphotransferese deficiency. We report here pathological findings of an autopsy case of mucolipidosis type II. The patient was an 8-year-old boy with mucolipidosis type II and was complicated with hypertrophic c...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2014.05.001
更新日期:2014-07-01 00:00:00
abstract::2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency, also known as beta-ketothiolase deficiency, is an inborn error of ketone body utilization and isoleucine catabolism. It is caused by mutations in the ACAT1 gene and may present with metabolic ketoacidosis. In order to obtain a more comprehensive view on this di...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2017.06.012
更新日期:2017-09-01 00:00:00
abstract::Increased glucose metabolism through the hexosamine pathway may result in insulin resistance, impaired insulin secretion, and diabetic nephropathy. We hypothesized that variants of GFPT1 encoding glutamine-fructose-6-phosphate amidotransferase, the rate limiting enzyme in this pathway, could increase GFPT1 gene expres...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2004.05.004
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND:Miller syndrome (post-axial acrofacial dysostosis) arises from gene mutations for the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). Nonetheless, despite demonstrated loss of enzyme activity dihydroorotate (DHO) has not been shown to accumulate, but paradoxically urine orotate has been reported t...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2016.06.008
更新日期:2016-09-01 00:00:00
abstract::Hypotonia-cystinuria syndrome (HCS) is an autosomal recessive disorder caused by combined deletions of SLC3A1 and PREPL. Clinical features include cystinuria, neonatal hypotonia with spontaneous improvement, poor feeding in neonates, hyperphagia in childhood, growth hormone deficiency, and variable cognitive problems....
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.06.011
更新日期:2012-11-01 00:00:00
abstract::Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by variable degrees of oculocutaneous albinism, easy bruisability, and bleeding as a result of deficient platelet dense bodies, and recurrent infections, with neutropenia, impaired chemotaxis and bactericidal activity, and abnormal NK ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1006/mgme.1999.2927
更新日期:1999-10-01 00:00:00
abstract::Phenylketonuria (PKU) is an autosomal recessive genetic disorder in which mutations in the phenylalanine-4-hydroxylase (PAH) gene result in an inactive enzyme (PAH, EC 1.14.16.1). The effect is an inability to metabolize phenylalanine (Phe), translating into elevated levels of Phe in the bloodstream (hyperphenylalanin...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2005.06.016
更新日期:2005-12-01 00:00:00
abstract::The bicistronic MOCS1 gene encodes two enzymatic activities that are necessary for the biosynthesis of the molybdenum cofactor (MoCo). Mutations in either of the two consecutive open reading frames are responsible for the majority of MoCo deficiency cases and result in a complementation group A phenotype. Two cDNA seq...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/s1096-7192(02)00100-2
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:Little is known about the consequences of the special energy enriched diet used to treat patients with phenylketonuria (PKU) in terms of obesity and metabolic syndrome (MetSyn) development. OBJECTIVE:To investigate the prevalence of overweight and obesity, and its consequences in terms of body composition a...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.10.006
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND & AIMS:Long-term liver-related complications of Gaucher disease (GD) include cirrhosis, portal hypertension and hepatocellular carcinoma. Although liver fibrosis is the main determinant of adverse liver-related clinical outcomes, it has rarely been evaluated in previously published cohorts of GD patients. We...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2018.08.004
更新日期:2018-09-01 00:00:00