Abstract：
:Inborn errors of purine metabolism exhibit broad neurological, immunological, haematological and renal manifestations. Limited awareness of the phenotypic spectrum, the recent descriptions of newer disorders and considerable genetic heterogeneity, have contributed to long diagnostic odysseys for affected individuals. These enzymes are widely but not ubiquitously distributed in human tissues and are crucial for synthesis of essential nucleotides, such as ATP, which form the basis of DNA and RNA, oxidative phosphorylation, signal transduction and a range of molecular synthetic processes. Depletion of nucleotides or accumulation of toxic intermediates contributes to the pathogenesis of these disorders. Maintenance of cellular nucleotides depends on the three aspects of metabolism of purines (and related pyrimidines): de novo synthesis, catabolism and recycling of these metabolites. At present, treatments for the clinically significant defects of the purine pathway are restricted: purine 5'-nucleotidase deficiency with uridine; familial juvenile hyperuricaemic nephropathy (FJHN), adenine phosphoribosyl transferase (APRT) deficiency, hypoxanthine phosphoribosyl transferase (HPRT) deficiency and phosphoribosyl-pyrophosphate synthetase superactivity (PRPS) with allopurinol; adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies have been treated by bone marrow transplantation (BMT), and ADA deficiency with enzyme replacement with polyethylene glycol (PEG)-ADA, or erythrocyte-encapsulated ADA; myeloadenylate deaminase (MADA) and adenylosuccinate lyase (ADSL) deficiencies have had trials of oral ribose; PRPS, HPRT and adenosine kinase (ADK) deficiencies with S-adenosylmethionine; and molybdenum cofactor deficiency of complementation group A (MOCODA) with cyclic pyranopterin monophosphate (cPMP). In this review we describe the known inborn errors of purine metabolism, their phenotypic presentations, established diagnostic methodology and recognised treatment options.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Balasubramaniam S,Duley JA,Christodoulou Jdoi
10.1007/s10545-014-9731-6subject
Has Abstractpub_date
2014-09-01 00:00:00pages
669-86issue
5eissn
0141-8955issn
1573-2665journal_volume
37pub_type
abstract：:Spastic paraparesis is a general term describing progressive stiffness and weakness in the lower limbs caused by pyramidal tract lesions. This clinical situation is frequently encountered in adult neurology. The diagnostic survey is usually limited to searching for acquired causes (spinal cord compression, inflammator...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-007-0745-1
更新日期：2007-11-01 00:00:00
abstract：:Ten of 31 patients with steroid sulphatase (STS) deficiency were found to have an allergic disease (bronchial asthma, allergic rhinitis, or atopic dermatitis). STS deficiency may predispose patients to allergic disease. ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005375902993
更新日期：1997-11-01 00:00:00
abstract：:One of the issues to be resolved in phenylketonuria is whether patients with mild hyperphenylalaninemia need treatment, or in other words, in what patients treatment needs to be started. Do patients need treatment when phenylalanine concentrations in blood are >360 μmol/L or >600 μmol/L? This paper reviews the literat...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-011-9283-y
更新日期：2011-06-01 00:00:00
abstract：:The mechanism of formation of extracellular fluid is first described, followed by an explanation of the relation between osmotic force, reflection coefficient and molecular size. The possible mechanism of brain extracellular fluid formation is then proposed in relation to the restriction offered by the blood-brain bar...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF00711896
更新日期：1993-01-01 00:00:00
abstract：:A brief outline of the known biochemical roles of manganese and chromium is given before the problems of determining human trace metal status are discussed. The factors predisposing to trace metal deficiency are reviewed but particular emphasis is placed upon those which alter the bioavailability of essential trace me...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF01811319
更新日期：1983-01-01 00:00:00
abstract：:Using a human dihydropteridine reductase (DHPR) cDNA, the frequency of restriction fragment length polymorphisms (RFLPs) with restriction endonucleases AvaII, MspI, NcoI and HinfI was estimated in unrelated, unaffected Japanese. The allele frequencies are different from those found in Caucasians, especially with MspI ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800212
更新日期：1990-01-01 00:00:00
abstract：:It has been suggested that the very low incidence of atherosclerosis in glycogen storage disease type Ia (GSD Ia) subjects might be attributed to elevated levels of uric acid, one of the potent low molecular- weight antioxidants found in plasma. The present communication describes a use of two analytical methods-cycli...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-009-1242-5
更新日期：2009-10-01 00:00:00
abstract：UNLABELLED:This report describes the clinical, biochemical and molecular data of a 78-year-old patient with xanthine dehydrogenase deficiency presenting as rheumatoid arthritis. BACKGROUND:Xanthinuria type I is a rare disorder of purine metabolism caused by xanthine dehydrogenase (XDH) deficiency; fewer than 150 cases...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-009-9011-z
更新日期：2010-12-01 00:00:00
abstract：:Sandhoff disease is caused by the defective activity of the lysosomal enzyme beta-hexosaminidase, resulting in accumulation of the glycolipids, GA2 and GM2. Niemann-Pick A/B disease is caused by the defective activity of lysosomal acid sphingomyelinase resulting in sphingomyelin accumulation. Pulmonary complications h...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/b:boli.0000042958.22066.6c
更新日期：2004-01-01 00:00:00
abstract：:Cardiovascular lesions, including coronary artery stenosis, are frequently associated and can cause sudden death in patients with genetic defects of glycosaminoglycan (GAG) metabolism. Early diagnosis of coronary artery lesions is difficult, although potentially lifesaving. Histopathological similarities between ather...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-013-9642-y
更新日期：2014-03-01 00:00:00
abstract：:We report a Brazilian girl who was diagnosed as having galactosialidosis (deficiency of protective protein/cathepsin A; PPCA deficiency; GS) at the age of 2 years 6 months during an extensive investigation for renal failure. She was found to have low levels of both β-galactosidase and α-neuraminidase in fibroblasts an...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-008-0730-3
更新日期：2008-12-01 00:00:00
abstract：:GM(2) gangliosidoses are a group of panethnic lysosomal storage diseases in which GM(2) ganglioside accumulates in the lysosome due to a defect in one of three genes, two of which encode the alpha- or beta-subunits of beta- N -acetylhexosaminidase (Hex) A. A small inframe deletion mutation in the catalytic domain of t...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/B:BOLI.0000045759.12935.76
更新日期：2004-01-01 00:00:00
abstract：:L-2-hydroxyglutaric aciduria (L-2-HGA) is a metabolic disease with an autosomal recessive mode of inheritance. It was first reported in 1980. Patients with this disease have mutations in both alleles of the L2HDGH gene. The clinical presentation of individuals with L-2-HGA is somewhat variable, but affected individual...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,多中心研究
doi：10.1007/s10545-008-0855-4
更新日期：2008-12-01 00:00:00
abstract：OBJECTIVE:There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) durin...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,多中心研究
doi：10.1007/s10545-016-9948-7
更新日期：2016-09-01 00:00:00
abstract：:5-Oxoprolinuria is primarily associated with inborn errors of the gamma-glutamyl cycle. In addition, transient 5-oxoprolinuria has been reported to occur in a variety of conditions, such as prematurity and malnutrition, and during medication. We report an unusual case of permanent 5-oxoprolinuria. The patient presente...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-006-0370-4
更新日期：2006-08-01 00:00:00
abstract：:The glycine uptake in cultured fibroblasts was studied in three children with non-ketotic hyperglycinaemia, one child with D-glyceric acidaemia and hyperglycinaemia and in six normal children, using an improved assay system giving individual protein correction. It was shown that all hyperglycinaemic children had norma...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF02338974
更新日期：1983-01-01 00:00:00
abstract：:The different long-chain fatty acid oxidation defects present with similar heterogeneous clinical phenotypes of different severity. Organs mainly affected comprise the heart, liver, and skeletal muscles. All symptoms are reversible with sufficient energy supply. In some long-chain fatty acid oxidation defects, disease...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-010-9090-x
更新日期：2010-10-01 00:00:00
abstract：:Direct alteration of a gene in the human genome requires an understanding of the role of the gene in metabolism. A gene may need to be introduced into a specific tissue or alternatively it may be possible to use accessible tissue such as bone marrow. The level of gene expression required also needs to be known as does...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800862
更新日期：1986-01-01 00:00:00
abstract：:The activity (mean +/- SD) of galactose-1-phosphate uridyl transferase in two long-term lymphoid cell lines from Caucasian patients with transferase deficiency galactosaemia, a heterozygote, and eight normal subjects was 0, 78 and 168 +/- 55 nmol UDPG consumed (mg protein)-1h-1, respectively. Also, no activity was fou...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799977
更新日期：1987-01-01 00:00:00
abstract：:Despite adequate dietary management, patients with classic galactosemia continue to have increased risks of cognitive deficits, speech dyspraxia, primary ovarian insufficiency, and abnormal motor development. A recent evaluation of a new galactose-1 phosphate uridylyltransferase (GALT)-deficient mouse model revealed r...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-016-9993-2
更新日期：2017-01-01 00:00:00
abstract：:Organic acidaemias can present with a wide variety of signs and symptoms. A survey of the clinical presentation of the organic acidurias shows that single symptoms are not characteristic or diagnostic. Clinical awareness coupled with appropriate laboratory investigation is required for the correct diagnosis to be reac...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF03047369
更新日期：1984-01-01 00:00:00
abstract：:This review surveys the potential application of gene therapy to metabolic diseases. Proof of principle has been achieved in the treatment of two inherited immunodeficiency conditions. A significant safety issue has also been observed. Several strategies are being experimentally tested for a number of metabolic diseas...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-006-0270-7
更新日期：2006-04-01 00:00:00
abstract：:For over two decades, nitisinone (NTBC) has been successfully used to manipulate the tyrosine degradation pathway and save the lives of many children with hereditary tyrosinaemia type 1. More recently, NTBC has been used to halt homogentisic acid accumulation in alkaptonuria (AKU) with evidence suggesting its efficacy...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1002/jimd.12229
更新日期：2020-09-01 00:00:00
abstract：BACKGROUND:Morphology and function of Fabry cardiomyopathy has been previously studied by echocardiography and cardiac magnetic resonance (CMR). However, the value of electrocardiography (ECG) in relation to these two techniques remains largely unknown. METHODS:One hundred fifty genetically confirmed Fabry patients we...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-012-9540-8
更新日期：2013-09-01 00:00:00
abstract：:Cystathionine beta synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Betaine supplementation, which can lower tHcy by stimulating homocysteine remethylation to methionine, is often given to CBS deficient patients in combination with other tre...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-015-9883-z
更新日期：2016-01-01 00:00:00
abstract：:Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) is a common genetic cause of increased homocysteine (HCY) levels. Post-methionine-load HCY concentrations allow identification of certain cases of hyperhomocysteinaemia ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005513626542
更新日期：1999-06-01 00:00:00
abstract：:The immunochemical analysis of enzyme from mucopolysaccharidoses (MPS) patients is aimed at defining the level and nature of the enzymically deficient protein produced by specific gene mutations. Immunochemical techniques allow purification of enzyme, characterization of the composite molecular species, measurement of...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF00711309
更新日期：1993-01-01 00:00:00
abstract：:Concentrations of free dolichol, total non-phosphorylated dolichol, and total phosphorylated dolichol were measured in autopsy specimens of brain and liver from ceroid-lipofuscinosis (CL) and control cases. Levels of non-phosphorylated dolichol, mainly as free dolichol, were increased approximately two-fold in late-in...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01805431
更新日期：1985-01-01 00:00:00
abstract：:Organic acidurias represent a group of inherited disorders resulting from deficient activity of specific enzymes of the catabolism of amino acids, carbohydrates or lipids, leading to tissue accumulation of one or more carboxylic (organic) acids. Patients affected by organic acidurias predominantly present neurological...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1023/B:BOLI.0000037353.13085.e2
更新日期：2004-01-01 00:00:00
abstract：:NTBC is a triketone with herbicidal activity that has been shown to have a novel mode of action by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase in plants. Early studies on the toxicity of this compound found that rats treated with NTBC developed corneal lesions. Investigations aimed at understanding the m...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1023/a:1005458703363
更新日期：1998-08-01 00:00:00
