Genetically transmitted error of metabolism of the
amino acid methionine characterized by severe myopia, Marfan-like stature
with pectus excavatum, slight mental retardation, and tendency to develop
spontaneous, generalized arterial, and venous thromboses under stress.
Cystathionine Beta-Synthetase (CBS) Deficiency; Homocystinemia.
Inborn error of metabolism of methionine that cannot be
converted to cysteine; methionine accumulates and cysteine is lacking. Left
untreated, this imbalance results in mental retardation, osteoporosis and
other bone problems, dislocated lenses of the eyes, heart disease, and
excessive blood clot formation.
Incidence in the general population is estimated at
between 1:50,000 and 1:200,000. Cystathionine β-synthase is a vitamin
B6-dependent enzyme; 50% of patients with homocystinuria show
pyridoxine responsiveness, including 13% who can be completely controlled
with pyridoxine alone.
Autosomal recessive. Chromosome 21q22. Carrier
detection possible using methionine loading tests. An abnormal gene on
chromosome 1 has been proposed as the cause of reduction in methylene
tetrahydrofolate reductase ([MTHFR] or homocystinuria III).
Deficiency of cystathionine synthase
(homocystinuria I) leads to a failure of transsulfuration of precursors of
cysteine, an important component of collagen. The weakened collagen is
responsible for many of the clinical manifestations. Two other interrelated
pathways of methionine metabolism can produce accumulation of homocysteine
and its metabolites: defective methylcobalamin synthesis (homocystinuria II)
and abnormality in MTHFR (homocystinuria III).
Confirmed by findings of homocystinuria and
methioninuria. P-methionine elevated in blood (up to 2 mmol/l). Homocystine,
mixed disulfide, and other sulfur-containing compounds may be present
(homocysteine binds to plasma proteins by disulfide bonds). Increased
amounts of methionine in
the cerebrospinal fluid (CSF)
(homocystine may be present). Prenatal
diagnosis possible by measuring enzyme activity in amniocytes.
Weakened collagen accounts for the clinical
manifestations of subluxation of lens of eye, generalized osteoporosis,
pectus excavatum, and marfanoid appearance (without joint
hyperextensibility). Mental retardation is common but may be prevented by
early dietary intervention. Breakage of collagen in blood vessel endothelium
leads to a high incidence of thromboembolic events, causing cerebrovascular
accident or myocardial infarction that frequently result in premature death
of patients. Management consists of a low-methionine diet with supplements
of cystine and betaine. Large doses of pyridoxine may control some of the
Patient should be receiving
appropriate diet, including pyridoxine supplements. Prolonged fasting should
be avoided because of risks of dehydration leading to hypercoagulability and
hypoglycemia. Dextrose-containing intravenous fluids should be started
preoperatively. Assess hematocrit, platelet count, and coagulation profile
(prothrombin time, partial thromboplastin time).
The major hazard in the perioperative
period is vascular thrombosis; this has been particularly associated with
angiography and the administration of nitrous oxide. The goals of anesthetic management are to maintain peripheral
perfusion and prevent dehydration. Agents should be selected to avoid
excessive depression of cardiac output. Fluid therapy should be started
preoperatively. Generous fluid therapy should be continued intraoperatively
to maintain circulating volume. Dextran-40 solutions have been advocated to ...