Molekulargenetisches Labor
Zentrum für Nephrologie und Stoffwechsel

Hyperhomozysteinämie bedingte Thrombose

Bei dem autosomal rezessiven Mangel an Cystathionin beta-Synthase kommt es zu einer Hyperhomozysteinämie die zu einer Thrombophilie führt. Für die Erkrankung sind Mutationen im CBS-Gen verantwortlich.

Gliederung

Venöse thromboembolische Erkrankungen
Autosomal dominanter Protein C-Mangel
Autosomal dominanter Protein S-Mangel
Autosomal rezessiver Protein C-Mangel
Autosomal rezessiver Protein S-Mangel
F2
F5
Faktor XII-Mangel
HABP2
Hyperhomozysteinämie bedingte Thrombose
CBS
Hypoplasminogenemie
MTHFR
PAI-Transkriptionsmodulator
Protein Z-Mangel
SERPINC1
THBD
Thrombophilie durch Heparin-Kofaktor 2-Mangel
VKORC1

Referenzen:

1.

Kim YJ et. al. (1974) On the mechanism of pyridoxine responsive homocystinuria. II. Properties of normal and mutant cystathionine beta-synthase from cultured fibroblasts.

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2.

Skovby F et. al. (1984) Homocystinuria: biogenesis of cystathionine beta-synthase subunits in cultured fibroblasts and in an in vitro translation system programmed with fibroblast messenger RNA.

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3.

Hu FL et. al. (1993) Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.

[^]
4.

Gallagher PM et. al. (1995) High frequency (71%) of cystathionine beta-synthase mutation G307S in Irish homocystinuria patients.

[^]
5.

Sebastio G et. al. (1995) The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations.

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6.

Watanabe M et. al. (1995) Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia.

[^]
7.

None (1994) Komrower Lecture. Molecular basis of phenotype expression in homocystinuria.

[^]
8.

Kruger WD et. al. (1995) A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene.

[^]
9.

Kluijtmans LA et. al. (1996) Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease.

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10.

Tsai MY et. al. (1996) High prevalence of a mutation in the cystathionine beta-synthase gene.

[^]
11.

Gaustadnes M et. al. (1999) Prevalence of congenital homocystinuria in Denmark.

[^]
12.

Kraus JP et. al. (1999) Cystathionine beta-synthase mutations in homocystinuria.

[^]
13.

Kluijtmans LA et. al. (1999) The molecular basis of cystathionine beta-synthase deficiency in Dutch patients with homocystinuria: effect of CBS genotype on biochemical and clinical phenotype and on response to treatment.

[^]
14.

Gaustadnes M et. al. (2000) Intermediate and severe hyperhomocysteinemia with thrombosis: a study of genetic determinants.

[^]
15.

Janosík M et. al. (2001) Impaired heme binding and aggregation of mutant cystathionine beta-synthase subunits in homocystinuria.

[^]
16.

Maclean KN et. al. (2002) High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations.

[^]
17.

Kelly PJ et. al. (2003) Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency.

[^]
18.

Kruger WD et. al. (2003) Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype.

[^]
19.

Wang L et. al. (2005) Expression of mutant human cystathionine beta-synthase rescues neonatal lethality but not homocystinuria in a mouse model.

[^]
20.

Lee SJ et. al. (2005) Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria.

[^]
21.

Urreizti R et. al. (2006) The p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America.

[^]
22.

Testai FD et. al. (2010) Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders.

[^]
23.

Mudd SH et. al. (1969) A derangement in B 12 metabolism leading to homocystinemia, cystathioninemia and methylmalonic aciduria.

[^]
24.

Fowler B et. al. (1978) Homocystinuria. Evidence for three distinct classes of cystathionine beta-synthase mutants in cultured fibroblasts.

[^]
25.

Almgren B et. al. (1978) Abdominal aortic aneurysm in homocystinuria.

[^]
26.

Wilcken DE et. al. (1976) The pathogenesis of coronary artery disease. A possible role for methionine metabolism.

[^]
27.

Uhlemann ER et. al. (1976) Platelet survival and morphology in homocystinuria due to cystathionine synthase deficiency.

[^]
28.

Collins JE et. al. (1990) Pancreatitis and homocystinuria.

[^]
29.

Cochran FB et. al. (1990) Pyridoxine-unresponsive homocystinuria with an unusual clinical course.

[^]
30.

Burke JP et. al. (1989) Ocular complications in homocystinuria--early and late treated.

[^]
31.

Malinow MR et. al. (1989) Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease.

[^]
32.

Abbott MH et. al. (1987) Psychiatric manifestations of homocystinuria due to cystathionine beta-synthase deficiency: prevalence, natural history, and relationship to neurologic impairment and vitamin B6-responsiveness.

[^]
33.

Kang SS et. al. (1986) Protein-bound homocyst(e)ine. A possible risk factor for coronary artery disease.

[^]
34.

None (1985) Homocystinuria. Clinical, biochemical and genetic aspects of cystathionine beta-synthase and its deficiency in man.

[^]
35.

Mudd SH et. al. (1985) The natural history of homocystinuria due to cystathionine beta-synthase deficiency.

[^]
36.

Wilcken DE et. al. (1985) Homocystinuria due to cystathionine beta-synthase deficiency--the effects of betaine treatment in pyridoxine-responsive patients.

[^]
37.

Boers GH et. al. (1985) Improved identification of heterozygotes for homocystinuria due to cystathionine synthase deficiency by the combination of methionine loading and enzyme determination in cultured fibroblasts.

[^]
38.

Boers GH et. al. (1985) Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease.

[^]
39.

None (1985) Vascular disease and homocysteine metabolism.

[^]
40.

Perry TL et. al. (1968) Treatment of homocystinuria with a low-methionine diet, supplemental cystine, and a methyl donor.

[^]
41.

Shipman RT et. al. (1969) Homocystinuria, addisonian pernicious anaemia, and partial deletion of a G chromosome.

[^]
42.

Harker LA et. al. (1974) Homocystinemia. Vascular injury and arterial thrombosis.

[^]
43.

Goldstein JL et. al. (1973) Homocystinuria: heterozygote detection using phytohemagglutinin-stimulated lymphocytes.

[^]
44.

Shelley WB et. al. (1972) Pyridoxine-dependent hair pigmentation in association with homocystinuria. The induction of melanotrichia.

[^]
45.

Mudd SH et. al. (1970) Homocystinuria due to cystathionine synthase deficiency: the effect of pyridoxine.

[^]
46.

Shih VE et. al. (1970) Pyridoxine-unresponsive homocystinuria.

[^]
47.

McCully KS et. al. (1970) Production of arteriosclerosis by homocysteinemia.

[^]
48.

Uhlendorf BW et. al. (1968) Cystathionine synthase in tissue culture derived from human skin: enzyme defect in homocystinuria.

[^]
49.

Carey MC et. al. (1968) Homocystinuria. II. Subnormal serum folate levels, increased folate clearance and effects of folic acid therapy.

[^]
50.

Carey MC et. al. (1968) Homocystinuria. I. A clinical and pathological study of nine subjects in six families.

[^]
51.

Wong PW et. al. (1968) The biosynthesis of cystathionine in patients with homocystinuria.

[^]
52.

None (1968) Activation of Hageman factor by L-homocystine.

[^]
53.

Kaeser AC et. al. (1969) Psychiatric and biochemical aspects of a case of homocystinuria.

[^]
54.

Carson NA et. al. (1969) Treatment of homocystinuria with pyridoxine. A preliminary study.

[^]
55.

None (1969) Homocystinuria: vitamin B6 dependent or not?

[^]
56.

None (1967) Dietary treatment of homocystinuria.

[^]
57.

Spaeth GL et. al. (1967) Prevalence of homocystinuria among the mentally retarded: evaluation of a specific screening test.

[^]
58.

Tada K et. al. (1967) Homocystinuria: amino acid pattern of the liver.

[^]
59.

None (1982) The nature of the ocular zonule.

[^]
60.

Munnich A et. al. (1983) Diet-responsive proconvertin (factor VII) deficiency in homocystinuria.

[^]
61.

Wilcken DE et. al. (1983) Homocystinuria--the effects of betaine in the treatment of patients not responsive to pyridoxine.

[^]
62.

Skovby F et. al. (1982) Immunochemical studies on cultured fibroblasts from patients with homocystinuria due to cystathionine beta-synthase deficiency.

[^]
63.

Mudd SH et. al. (1981) A study of cardiovascular risk in heterozygotes for homocystinuria.

[^]
64.

Kurczynski TW et. al. (1980) Maternal homocystinuria: studies of an untreated mother and fetus.

[^]
65.

Mudd SH et. al. (1995) Plasma homocyst(e)ine or homocysteine?

[^]
66.

Reish O et. al. (1995) Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency.

[^]
67.

Kozich V et. al. (1995) Hyperhomocysteinemia in premature arterial disease: examination of cystathionine beta-synthase alleles at the molecular level.

[^]
68.

Malinow MR et. al. (1994) Role of plasma homocyst(e)ine in arterial occlusive diseases.

[^]
69.

Di Minno G et. al. (1993) Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and probucol-sensitive mechanism.

[^]
70.

None (1996) Nutritional ecogenetics: homocysteine-related arteriosclerotic vascular disease, neural tube defects, and folic acid.

[^]
71.

Mandel H et. al. (1996) Coexistence of hereditary homocystinuria and factor V Leiden--effect on thrombosis.

[^]
72.

Lubec B et. al. (1996) Evidence for McKusick's hypothesis of deficient collagen cross-linking in patients with homocystinuria.

[^]
73.

Bass HN et. al. (1997) Spontaneous pneumothorax in association with pyridoxine-responsive homocystinuria.

[^]
74.

None (1998) Ocular complications and a new surgical approach to lens dislocation in homocystinuria due to cystathionine-beta-synthetase deficiency.

[^]
75.

Nugent A et. al. (1998) Long-term survival of homocystinuria: the first case.

[^]
76.

Harrison DA et. al. (1998) Management of ophthalmic complications of homocystinuria.

[^]
77.

Yap S et. al. (1998) Homocystinuria due to cystathionine beta-synthase deficiency in Ireland: 25 years' experience of a newborn screened and treated population with reference to clinical outcome and biochemical control.

[^]
78.

Gallagher PM et. al. (1998) Characterization of mutations in the cystathionine beta-synthase gene in Irish patients with homocystinuria.

[^]
79.

Chao CL et. al. (1999) The graded effect of hyperhomocysteinemia on the severity and extent of coronary atherosclerosis.

[^]
80.

Peterschmitt MJ et. al. (1999) Reduction of false negative results in screening of newborns for homocystinuria.

[^]
81.

Guttormsen AB et. al. (2001) Disposition of homocysteine in subjects heterozygous for homocystinuria due to cystathionine beta-synthase deficiency: relationship between genotype and phenotype.

[^]
82.

Werstuck GH et. al. (2001) Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways.

[^]
83.

Yap S et. al. (2001) The intellectual abilities of early-treated individuals with pyridoxine-nonresponsive homocystinuria due to cystathionine beta-synthase deficiency.

[^]
84.

Schnyder G et. al. (2001) Decreased rate of coronary restenosis after lowering of plasma homocysteine levels.

[^]
85.

Yaghmai R et. al. (2002) Progressive cerebral edema associated with high methionine levels and betaine therapy in a patient with cystathionine beta-synthase (CBS) deficiency.

[^]
86.

Pullin CH et. al. (2002) Vitamin C therapy ameliorates vascular endothelial dysfunction in treated patients with homocystinuria.

[^]
87.

Gaustadnes M et. al. (2002) The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment.

[^]
88.

Levy HL et. al. (2002) Reproductive fitness in maternal homocystinuria due to cystathionine beta-synthase deficiency.

[^]
89.

GERRITSEN T et. al. (1962) The identification of homocystine in the urine.

[^]
90.

CARSON NA et. al. (1962) Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland.

[^]
91.

CARSON NA et. al. (1963) HOMOCYSTINURIA: A NEW INBORN ERROR OF METABOLISM ASSOCIATED WITH MENTAL DEFICIENCY.

[^]
92.

MUDD SH et. al. (1964) HOMOCYSTINURIA: AN ENZYMATIC DEFECT.

[^]
93.

SCHIMKE RN et. al. (1965) HOMOCYSTINURIA. STUDIES OF 20 FAMILIES WITH 38 AFFECTED MEMBERS.

[^]
94.

None (1959) Renal abnormalities in the Marfan syndrome.

[^]
95.

Hubmacher D et. al. (2005) Modification of the structure and function of fibrillin-1 by homocysteine suggests a potential pathogenetic mechanism in homocystinuria.

[^]
96.

Elsaid MF et. al. () Are heterocygotes for classical homocystinuria at risk of vitamin B12 and folic acid deficiency?

[^]
97.

Jakubowski H et. al. (2008) Mutations in cystathionine beta-synthase or methylenetetrahydrofolate reductase gene increase N-homocysteinylated protein levels in humans.

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Update: 27. März 2019