Disease relevance of Homocystinuria

• A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurologic abnormalities in a vitamin B12-deficient breast-fed infant of a strict vegetarian [1].
• One patient with prenatally diagnosed homocystinuria who was also heterozygous for factor V Leiden has received warfarin therapy since birth and has not had thrombosis (age, 18 months) [2].
• Accordingly, homocysteine neurotoxicity through overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both homocystinuria and modest hyperhomocysteinemia [3].
• Severely elevated levels of total homocysteine (approximately millimolar) in the blood typify the childhood disease homocystinuria, whereas modest levels (tens of micromolar) are commonly found in adults who are at increased risk for vascular disease and stroke [3].
• Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency [4].

Psychiatry related information on Homocystinuria

• These diseases are seen as clinical counterparts of the main manifestations of homocystinuria (vascular occlusions of arteries and veins, mental retardation, osteoporosis and ectopia lentis, respectively) that develop only after many years of exposure to moderately elevated homocysteine (Hcy) levels [5].
• CONCLUSIONS: PK-PD modelling allows recommendations for optimal dosage of betaine in the treatment of homocystinuria, that have the potential for improved patient compliance and both therapeutic and pharmacoeconomic benefit [6].
• Functional methionine synthase deficiency due to abnormal methylcobalamin metabolism causes megaloblastic anemia, moderate to severe developmental delay, lethargy, and anorexia in association with homocystinuria [7].
• Diseases such as MSUD, 6 PTSD, Sanfilippo syndrome type B, methylmalonic acidemia, homocystinuria, GM2 gangliosidosis Sandhoff variant, infantile central nervous system spongy degeneration (Canavan disease), and neuraminidase deficiency showed definite tribal occurrence [8].

High impact information on Homocystinuria

• Homocystinuria due to cystathionine beta-synthase deficiency was confirmed by quantitative amino acid analyses [9].
• Mutations in cystathionine beta-synthase (CBS) are known to cause homocystinuria, a recessive disorder characterized by excessive levels of total homocysteine (tHcy) in plasma [10].
• We determined activated partial-thromboplastin times in the presence and absence of activated protein C and tested for the factor V Leiden mutation in 45 members of seven unrelated consanguineous kindreds in which at least 1 member was homozygous for homocystinuria [2].
• Premature arteriosclerosis and thromboembolic events are well-known complications of homozygous homocystinuria due to cystathionine synthase deficiency [11].
• Betaine in the treatment of homocystinuria [12].

Chemical compound and disease context of Homocystinuria

• We conclude that treatment of homocystinuria that is not responsive to pyridoxine and of disorders of homocysteine remethylation should include betaine in adequate doses to ensure maximum lowering of elevated plasma homocysteine levels [13].
• Methyltetrahydrofolate is used for the methylation of homocysteine to methionine, and a deficiency of this compound could explain the homocystinemia and homocystinuria [14].
• The treatment of homocystinuria that is not responsive to pyridoxine is not usually biochemically or clinically successful, and vascular, ocular, and skeletal complications commonly supervene [13].
• Folate-responsive homocystinuria and "schizophrenia". A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity [14].
• He was found to have methylmalonic aciduria (79 mumol per milligram of creatinine) and homocystinuria (0.85 mumol per milligram of creatinine) [1].

Biological context of Homocystinuria

• 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 [15].
• The mother, an obligate heterozygote, was free from all signs of homocystinuria; nonetheless, extracts of her fibroblasts were devoid of CBS protein and activity [16].
• We used SSCP to survey reverse transcribed-PCR amplified cystathionine synthase cDNAs from patients with homocystinuria [17].
• The Italian patient 2241, an A114V+R58W/M126V compound heterozygote, exhibited severe pyridoxine nonresponsive homocystinuria, while another Italian patient 2242, with an A114V/E302K genotype, responded to pyridoxine treatment and had a much milder phenotype [18].
• Mutational analysis of the cystathionine beta-synthase gene: a splicing mutation, two missense mutations and an insertion in patients with homocystinuria. Mutations in brief no. 120. Online [19].

Anatomical context of Homocystinuria

• Affinity of cystathionine beta-synthase for pyridoxal 5'-phosphate in cultured cells. A mechanism for pyridoxine-responsive homocystinuria [20].
• Fibroblast extracts from 20 individuals with homocystinuria due to cystathionine beta-synthase deficiency were analyzed for the presence of immunoreactive synthase antigen as cross-reacting material (CRM) [21].
• CBS deficiency is associated with homocystinuria, which is known to affect various physiological systems, including the central nervous system [22].
• We have found that homocysteine directly injures human endothelium, which may account for the premature arterial disease in homocystinuria [23].
• Patients with homocystinuria due to homozygosis for cystathionine beta-synthase deficiency seldom have plaques in their carotid arteries [24].

Gene context of Homocystinuria

• Patients with an autosomal recessive severe deficiency of MTHFR have homocystinuria and a wide range of neurological and vascular disturbances [25].
• Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria [26].
• Homocysteine, one of the substrates of CBS, is known to accumulate in homocystinuria and is metabolized to homocysteate and homocysteine sulphinate, both known to be powerful excitotoxic amino acids [22].
• Our study expands the knowledge of the phenotypic and genotypic variability of the cblE type of homocystinuria and supports the concept that this disorder is caused by mutations in the MTRR gene [27].
• Severe MTHFR deficiency results in homocystinuria, an inborn error of metabolism with neurological and vascular complications [28].

Analytical, diagnostic and therapeutic context of Homocystinuria

• RT-PCR and direct sequence analyses were used to define mutations in the cystathionine beta-synthase (CBS) gene in two unrelated male patients with vitamin B6 nonresponsive homocystinuria [19].
• Early diagnosis and improved treatment are leading to the potential for increased reproductive capability in homocystinuria due to cystathionine beta-synthase (CbetaS) deficiency, but information about reproductive outcome and risk of thromboembolism in pregnancy is limited [29].
• CblE type of homocystinuria due to methionine synthase reductase deficiency: clinical and molecular studies and prenatal diagnosis in two families [27].
• Determination of total homocysteine in dried blood spots using high performance liquid chromatography for homocystinuria newborn screening [30].
• General anesthesia for patient with type III homocystinuria (tetrahydrofolate reductase deficiency) [31].

References