Abstract:
BACKGROUND:One major problem of using hypercholesterolaemia alone as a primary criterion for diagnosing familial hypercholesterolaemia (FH) is that 15-40% of relatives may be misdiagnosed because plasma lipid levels in FH heterozygotes overlap with those in the general population. SETTING:General Hospital/University of Vienna, Department of Pediatrics, Outpatient lipid clinic. METHODS:As a part of the MED-PED (make early diagnosis-prevent early death) project we are currently investigating children, adolescents and their relatives who are suspected to be affected with FH in our out-patient clinic for metabolic diseases using MED-PED inclusion criteria and confirming the diagnosis by means of DNA analysis. PATIENTS:263 patients with premature atherosclerosis and/or hypercholesterolaemia: 116 children (mean age 11.6 +/- 4.1 years; 57 girls and 59 boys) and 147 adults (64 women, mean age 41.5 +/- 13.7 years; 83 men, mean age 42.8 +/- 10.8 years). RESULTS:119 patients with mutations have been detected; 56 children with either low density lipoprotein receptor (LDLR) and/or ApoB mutations (27 girls and 29 boys; mean total cholesterol (TC) 275 +/- 71 mg/dl, triglycerides (TG) 101 +/- 57 mg/dl, high-density lipoprotein cholesterol (HDL-C) 49 +/- 12 mg/dl, low-density lipoprotein cholesterol (LDL-C) 198 +/- 67 mg/dl) and one boy with a homozygous. LDLR mutation. A further 62 adults with LDLR and/or ApoB mutations were documented; 33 women (mean age 36.9 +/- 11.1 years; mean TC 283 +/- 76 mg/dl, TG 137 +/- 78 mg/dl, HDL-C 55 +/- 17 mg/dl, LDL-C 210 +/- 67 mg/dl) and 29 men (mean age 45.0 +/- 10.6 years; mean TC 301 +/- 87 mg/dl, TG 163 +/- 112 mg/dl, HDL-C 42 +/- 12 mg/dl, LDL-C 233 +/- 83 mg/dl). In 32 of these subjects (11 children (21%), 21 adults (42%)), serum lipid levels were lower than the diagnostic MED-PED limits adopted, so that they might have been misclassified without an additional DNA analysis. CONCLUSION:In our study, diagnosis of FH and related disorders (ApoB-100 defect) by means of conventional laboratory methods missed at least 21% in children and 42% in adults affected with LDLR and/or ApoB gene mutations. Genetic FH diagnosis provides a tool for specific diagnosis of mutation carrier status.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Widhalm K,Dirisamer A,Lindemayr A,Kostner Gdoi
10.1007/s10545-007-0563-5subject
Has Abstractpub_date
2007-04-01 00:00:00pages
239-47issue
2eissn
0141-8955issn
1573-2665journal_volume
30pub_type
杂志文章abstract::Niemann-Pick disease type C (NPC) is a neurovisceral storage disorder with an unknown primary deficiency. Somatic cell hybridization experiments using human cultured fibroblasts have shown that two complementation groups (NPC-alpha and NPC-beta) are associated with the biochemical and clinical phenotypes comprising NP...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799171
更新日期:1996-01-01 00:00:00
abstract::The differential diagnosis of patients with apparent congenital lactic acidoses poses one of the most intractable problems in the study of patients with disorders of organic acid metabolism. An outline of the factors leading to a lactic acidosis, particularly in infants and young children, together with a brief review...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF03047380
更新日期:1984-01-01 00:00:00
abstract::There is paucity of literature on dietary treatment in glycogen storage disease (GSD) type IV and formal guidelines are not available. Traditionally, liver transplantation was considered the only treatment option for GSD IV. In light of the success of dietary treatment for the other hepatic forms of GSD, we have initi...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1002/jimd.12339
更新日期:2020-12-17 00:00:00
abstract::Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined im...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-013-9664-5
更新日期:2014-05-01 00:00:00
abstract::Maple syrup urine disease (MSUD), an inborn error of amino acids catabolism is characterized by accumulation of branched chain amino acids (BCAAs) leucine, isoleucine, valine and their corresponding alpha-ketoacids. Impact on the cognitive development has been reported historically, with developmental delays of varyin...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,多中心研究
doi:10.1007/s10545-017-0033-7
更新日期:2017-05-01 00:00:00
abstract::A case of pyruvate dehydrogenase E3 binding protein deficiency is reported in a 24-year-old male with encephalomyopathy. Blood lactate was only minimally elevated, as was alanine. ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1025181512847
更新日期:2003-01-01 00:00:00
abstract::This retrospective study in 20 untreated type I Gaucher disease patients shows that in Dutch patients clinical manifestations of Gaucher disease type I are progressive in the majority of patients, children as well as adults. This is in contrast with studies among Jewish patients. Our results emphasize the need for a r...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005655031239
更新日期:2000-02-01 00:00:00
abstract::Lyso-globotriaosylsphingosine (lyso-Gb3) is a useful biomarker in the diagnosis and monitoring of treatment for Fabry disease. However, it is unclear whether lyso-Gb3 is elevated in patients with later-onset Fabry disease. Thus, we measured lyso-Gb3 levels from dried blood spots (DBS) from male newborns with the Fabry...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-012-9547-1
更新日期:2013-09-01 00:00:00
abstract::DNA sequence analyses have become a major component in the diagnostic work-up of patients; however, limited consideration appears to be given to the possibility that reported results may in fact be wrong. Over the last four years we have carried out an External Quality Assessment scheme for mutation analysis in phenyl...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-008-1052-1
更新日期:2008-12-01 00:00:00
abstract::A 32 year-old asymptomatic male came to our attention with a 21-year history, documented elsewhere, of puzzling increases in his serum transaminase level. At first, very low serum ceruloplasmin level suggested Wilson disease. Two liver biopsies showed mild portal inflammation, steatosis and mild fibrosis. Further inve...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-008-1004-9
更新日期:2008-12-01 00:00:00
abstract::This first detailed report of a female patient with functional methionine synthase deficiency due to the cblE defect describes treatment with several vitamins and cofactors and clinical progress for 17 years. Before treatment, major findings were microcephaly, psychomotor retardation, episodic reduced consciousness, m...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005372730310
更新日期:1997-11-01 00:00:00
abstract::Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid beta-glucosidase. The most prevalent mutant genotype in type I Gaucher disease, N370S/N370S, is commonly thought to confer a mild phenotype presenting in adulthood. To characterize a subset of more severely affected N370S homozyg...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-008-0868-z
更新日期:2008-12-01 00:00:00
abstract::A patient with hyperuricaemia and gouty arthritis due to a new variant of hypoxanthine-guanine phosphoribosyltransferase is described. The mutation (I136T, HPRT Marseille) is in the phosphoribosylpyrophosphate-binding region of the gene and leads to almost total loss of enzyme activity in erythrocytes, with 5% in lymp...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/b:boli.0000037399.72152.a9
更新日期:2004-01-01 00:00:00
abstract::We report a retrospective electron-microscopical study of liver biopsies and fibroblast cultures of 19 patients with congenital disorders of glycosylation (CDG) of different subtypes. A constant finding in liver biopsies of all CDG-I cases was that of abnormal lysosomal lamellar inclusions in the hepatocytes, which we...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1024023429680
更新日期:2003-01-01 00:00:00
abstract::Untreated pregnancies and their outcomes were studied in 10 women with histidinaemia and their 26 pregnancies. The mean maternal assigned histidine level was 727+/-186 micromol/L (range 484-1,053). Six women had classic histidinaemia (assigned level >700 micromol/L) and the remaining four had mild (atypical) histidina...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/B:BOLI.0000028783.35805.dd
更新日期:2004-01-01 00:00:00
abstract::This study aimed to evaluate systematically the effect of the free use of fruits and vegetables containing an intermediate amount of phenylalanine (51-100 mg/100 g) on the biochemical control in children with phenylketonuria (PKU). Fifteen subjects with PKU, with a median age of 6 years (range 1-24 years) were studied...
journal_title:Journal of inherited metabolic disease
pub_type: 临床试验,杂志文章
doi:10.1023/a:1025150901439
更新日期:2003-01-01 00:00:00
abstract::There are two mechanisms for glucose transport across cell membranes. In the intestine and renal proximal tubule, glucose is transported against a concentration gradient by a secondary active transport mechanism in which glucose is cotransported with sodium ions. In all other cells, glucose transport is mediated by on...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1023/a:1005632012591
更新日期:2000-05-01 00:00:00
abstract::There is now strong evidence for the implication of collagen alpha 1(I), alpha 2(I) and alpha 1(III) mutations in many forms of osteogenesis imperfecta and inherited arterial aneurysms (Ehlers Danlos syndrome type IV). A sizeable proportion of these disorders have detectable abnormalities by conventional protein chemi...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF01799292
更新日期:1989-01-01 00:00:00
abstract::Sjögren-Larsson syndrome (SLS) is a rare neurometabolic syndrome caused by deficient fatty aldehyde dehydrogenase. Patients exhibit intellectual disability, spastic paraplegia, and ichthyosis. The accumulation of fatty alcohols and fatty aldehydes has been demonstrated in plasma and skin but never in brain. Brain magn...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1002/jimd.12275
更新日期:2020-11-01 00:00:00
abstract::A sensitive and selective analytical technique is described for the determination of N-acetylaspartic acid in body fluids using stable isotope dilution in combination with positive chemical ionization mass spectrometry with selected ion monitoring. Control mean and ranges have been established: in urine 19.5 and 6.6-3...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799929
更新日期:1991-01-01 00:00:00
abstract::Aspartylglycosaminuria (AGU) is a lysosomal storage disease caused by deficient activity of glycosylasparaginase (AGA), and characterized by motor and mental retardation. Enzyme replacement therapy (ERT) in adult AGU mice with AGA removes the accumulating substance aspartylglucosamine from and reverses pathology in ma...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-010-9158-7
更新日期:2010-10-01 00:00:00
abstract::Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism, glycolysis, and protein glycosylation. Previously known as GSD XIV, it was recently reclassified as a congenital disorder of glycosylation, PGM1-CDG. PGM1-CDG usually manifests as a multisystem disease. Most patients pr...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1002/jimd.12286
更新日期:2021-01-01 00:00:00
abstract::Results are presented of alpha-L-iduronidase assays in the leukocytes of normal individuals, patients with Hurler disease and heterozygous carriers. The assays were carried out using 4-methylumbelliferyl-alpha-L-iduronide and 4-trifluoromethylumbelliferyl-alpha-L-iduronide as substrates. It was shown that 4-trifluorom...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01800585
更新日期:1991-01-01 00:00:00
abstract:BACKGROUND:Aromatic L-amino acid decarboxylase (AADC) deficiency is a disorder of biogenic amine metabolism resulting in generalized combined deficiency of serotonin, dopamine and catecholamines. Main clinical features are developmental delay, muscular hypotonia, dystonia, oculogyric crises and additional extraneurolog...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-009-1076-1
更新日期:2009-06-01 00:00:00
abstract::Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase A activity, which leads to accumulation of glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. The effect of this accumulation on peripheral and cardiac vascular function is poorly...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-005-0563-2
更新日期:2005-01-01 00:00:00
abstract::The congenital disorders of glycosylation (CDG) are inborn errors of metabolism with a great genetic heterogeneity. Most CDG are caused by defects in the N-glycan biosynthesis, leading to multisystem phenotypes. However, the occurrence of tissue-restricted clinical symptoms in the various defects in dolichol-phosphate...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1002/jimd.12095
更新日期:2019-09-01 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::An adult patient with hereditary tyrosinaemia type I who developed renal failure is reported. She received a renal transplant at the age of 23 years. In childhood her kidney disease was dominated by multiple tubular defects with resulting hypophosphataemic rickets. Metabolic acidosis was the most prominent feature in ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01804389
更新日期:1991-01-01 00:00:00
abstract::In patients with cerebro-hepato-renal (Zellweger) syndrome, the absence of peroxisomes results in an impairment of metabolic processes in which peroxisomes are normally involved. These include the catabolism of very long chain (greater than C22) fatty acids, the biosynthesis of ether-phospholipids and of bile acids, t...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF01812845
更新日期:1987-01-01 00:00:00
abstract::Diagnostic information is supplied for the early detection of subacute and chronic forms of type I tyrosinaemia. ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799947
更新日期:1991-01-01 00:00:00