PMID- 11011851
OWN - NLM
STAT- MEDLINE
DCOM- 20010208
LR  - 20151119
IS  - 0094-6176 (Print)
IS  - 0094-6176 (Linking)
VI  - 26
IP  - 3
DP  - 2000
TI  - Vascular complications of severe hyperhomocysteinemia in patients with 
      homocystinuria due to cystathionine beta-synthase deficiency: effects of 
      homocysteine-lowering therapy.
PG  - 335-40
AB  - Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency leads to 
      severe hyperhomocysteinemia (HHcy). Vascular events (VE) remain the major cause 
      of morbidity and mortality in the untreated patients with HCU. The study on the 
      natural history of untreated HCU disclosed that, at the time of maximal risk, in 
      other words beyond 10 years old, there was one event per 25 years. Recent studies 
      from Australia (n = 32), The Netherlands (n = 28), and Ireland (n = 24) have 
      documented the effects of long-term treatment on the vascular outcome of a total 
      of 84 patients with 1314 patient-years of treatment for HCU. The mean (range) age 
      was 27.8 (2.5 to 70) years. Five VE were recorded during treatment; one pulmonary 
      embolism, two myocardial infarctions, and two abdominal aneurysms. All five VE 
      occurred in B6-responsive patients at a mean (range) age of 48.8 (30 to 60) 
      years. In 1314 patient-years of treatment, 53 VE would have been expected if they 
      remained untreated; instead only 5 were documented, relative risk = 0.091 (95% 
      confidence interval [CI] 0.043 to 0.190; p < 0.001). Appropriate 
      homocysteine-lowering therapy for severe HHcy significantly reduced the vascular 
      risk in patients with HCU. VE were rare with treatment despite the fact that the 
      post-treatment homocysteine levels were several times higher than the cutoff 
      point for homocysteine in the normal population. The present findings may have 
      relevance to the current concept of "mild HHcy" as a risk factor for vascular 
      disease, with elevated plasma homocysteine levels considerably lower than that of 
      the post-treatment levels in this group of reported patients.
FAU - Yap, S
AU  - Yap S
AD  - National Center for Inherited Metabolic Disorders, The Children's Hospital, 
      Dublin, Ireland.
FAU - Naughten, E R
AU  - Naughten ER
FAU - Wilcken, B
AU  - Wilcken B
FAU - Wilcken, D E
AU  - Wilcken DE
FAU - Boers, G H
AU  - Boers GH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Semin Thromb Hemost
JT  - Seminars in thrombosis and hemostasis
JID - 0431155
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 48TCX9A1VT (Cystine)
RN  - 935E97BOY8 (Folic Acid)
RN  - AE28F7PNPL (Methionine)
RN  - KV2JZ1BI6Z (Pyridoxine)
RN  - P6YC3EG204 (Vitamin B 12)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Australia/epidemiology
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Cystine/therapeutic use
MH  - Drug Resistance
MH  - Female
MH  - Folic Acid/therapeutic use
MH  - Follow-Up Studies
MH  - Genetic Predisposition to Disease
MH  - Homocysteine/metabolism
MH  - Homocystinuria/blood/*complications/genetics
MH  - Humans
MH  - Hyperhomocysteinemia/*complications/diet therapy/drug therapy
MH  - Infant
MH  - Ireland/epidemiology
MH  - Male
MH  - Methionine/administration & dosage
MH  - Middle Aged
MH  - Netherlands/epidemiology
MH  - Pyridoxine/therapeutic use
MH  - Risk
MH  - Risk Factors
MH  - Thrombophilia/epidemiology/*etiology/prevention & control
MH  - Vascular Diseases/epidemiology/*etiology/prevention & control
MH  - Vitamin B 12/therapeutic use
RF  - 28
EDAT- 2000/09/30 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/09/30 11:00
PHST- 2000/09/30 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/09/30 11:00 [entrez]
AID - 10.1055/s-2000-8100 [doi]
PST - ppublish
SO  - Semin Thromb Hemost. 2000;26(3):335-40. doi: 10.1055/s-2000-8100.