The natural history of homocystinuria due to cystathionine beta-synthase deficiency
- PMID: 3872065
- PMCID: PMC1684548
The natural history of homocystinuria due to cystathionine beta-synthase deficiency
Abstract
An international questionnaire survey has been conducted to define better the natural history of homocystinuria due to cystathionine beta-synthase deficiency and permit evaluation of treatment. Data were compiled for 629 patients. Among patients not discovered by newborn screening, B6-responsive individuals on the average have significantly better mental capabilities (mean IQ, 79) than do B6-nonresponsive individuals (mean IQ, 57). Time-to-event curves are presented for the other major clinical abnormalities produced by this disease. Each occurred at significantly lower rates in untreated B6-responsive than in untreated B6-nonresponsive patients, as shown by the following examples: (1) dislocation of optic lenses (at age 10, chances of dislocation: 55% and 82%, respectively); (2) initial clinically detected thromboembolic events (at age 15, chances of having had such an event: 12% and 27%, respectively); (3) radiologic detection of spinal osteoporosis (at age 15, chances of such osteoporosis having been detected: 36% and 64%, respectively); and (4) mortality (at age 30, chances of not surviving: 4% and 23%, respectively). Methionine restriction initiated neonatally prevented mental retardation, retarded the rate of lens dislocation, and may have reduced the incidence of seizures. Pyridoxine treatment of late-detected B6-responsive patients retarded the rate of occurrence of initial thromboembolic events. Following 586 surgical procedures, 25 postoperative thromboembolic complications occurred, six of which were fatal. Reproductive histories were reported predominantly for B6-responsive patients. Living offspring of either men or women patients had few abnormalities. The evidence is inconclusive whether untreated maternal cystathionine beta-synthase deficiency leads to excessive fetal loss. Only 13% of patients detected in screening programs of newborns and classified as to B6-responsiveness were B6-responsive, compared to 47% among late-detected patients. Current screening programs that identify neonatal hypermethioninemia may be preferentially failing to detect B6-responsive patients.
Similar articles
-
Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency.2004 Jan 15 [updated 2017 May 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2004 Jan 15 [updated 2017 May 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301697 Free Books & Documents. Review.
-
Reproductive fitness in maternal homocystinuria due to cystathionine beta-synthase deficiency.J Inherit Metab Dis. 2002 Aug;25(4):299-314. doi: 10.1023/a:1016502408305. J Inherit Metab Dis. 2002. PMID: 12227460
-
The intellectual abilities of early-treated individuals with pyridoxine-nonresponsive homocystinuria due to cystathionine beta-synthase deficiency.J Inherit Metab Dis. 2001 Aug;24(4):437-47. doi: 10.1023/a:1010525528842. J Inherit Metab Dis. 2001. PMID: 11596648
-
Vascular complications of severe hyperhomocysteinemia in patients with homocystinuria due to cystathionine beta-synthase deficiency: effects of homocysteine-lowering therapy.Semin Thromb Hemost. 2000;26(3):335-40. doi: 10.1055/s-2000-8100. Semin Thromb Hemost. 2000. PMID: 11011851 Review.
-
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.J Inherit Metab Dis. 1998 Oct;21(7):738-47. doi: 10.1023/a:1005445132327. J Inherit Metab Dis. 1998. PMID: 9819703
Cited by
-
A refined total capsular bag suspension technique for lens subluxation from cystathionine beta-synthase deficiency: A case report and literature review.Am J Ophthalmol Case Rep. 2024 Mar 14;34:102042. doi: 10.1016/j.ajoc.2024.102042. eCollection 2024 Jun. Am J Ophthalmol Case Rep. 2024. PMID: 38544915 Free PMC article.
-
Moderate Elevation of Homocysteine Induces Endothelial Dysfunction through Adaptive UPR Activation and Metabolic Rewiring.Cells. 2024 Jan 24;13(3):214. doi: 10.3390/cells13030214. Cells. 2024. PMID: 38334606 Free PMC article.
-
Hyperhomocysteinemia in Adult Patients: A Treatable Metabolic Condition.Nutrients. 2023 Dec 30;16(1):135. doi: 10.3390/nu16010135. Nutrients. 2023. PMID: 38201964 Free PMC article. Review.
-
Genetic and Pharmacological Modulation of Cellular Proteostasis Leads to Partial Functional Rescue of Homocystinuria-Causing Cystathionine-Beta Synthase Variants.Mol Cell Biol. 2023;43(12):664-674. doi: 10.1080/10985549.2023.2284147. Epub 2023 Dec 20. Mol Cell Biol. 2023. PMID: 38051092 Free PMC article.
-
Inborn errors of amino acid metabolism - from underlying pathophysiology to therapeutic advances.Dis Model Mech. 2023 Nov 1;16(11):dmm050233. doi: 10.1242/dmm.050233. Epub 2023 Nov 23. Dis Model Mech. 2023. PMID: 37994477 Free PMC article.
References
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical