42. Homocystinuria
Definition
Homocystinuria is an autosomal recessive disorder of methionine metabolism that produces an abnormal accumulation of homocystine, homocysteine-cysteine complex, and other metabolites in the blood and urine.
Incidence
The incidence of homocystinuria is variable, with reports between 1:50,000 to 1:200,000.
Etiology
Homocystinuria is an autosomal recessive inherited defect in either the transsulfuration pathway or methylation pathway, producing deficiencies of cystathionine beta-synthase enzyme, defective methylcobalamin synthesis, or an abnormality of methylene tetrahydrofolate reductase.
Signs and Symptoms
• Ectopia lentis
• Genu valgum
• Kyphoscoliosis
• Kyphosis
• Marfanoid habitus
• Mental retardation
• Osteoporosis
• Pes carinatum
• Pes excavatum
• Seizures
• Signs and symptoms of stroke (hemiplegia, aphasia, ataxia, pseudobulbar palsy)
Medical Management
The medication of choice for treatment of homocystinuria is pyridoxine, between 100 to 500 mg/day in divided doses. Vitamin B 12 and folic acid may be added to the treatment regimen if pyridoxine is not effective in controlling the levels of homocystine.
Some patients are sensitive to pyridoxine. In such cases, dietary restrictions on methionine intake are instituted along with administration of betaine supplements to reduce homocystine levels.
Complications
• Deep vein thrombosis
• Hypoglycemia
• Stroke
• Thromboembolism
Anesthesia Implications
Thromboembolism is a major concern for patients with homocystinuria. Vascular occlusion of any major organ (heart, lungs, brain, or kidney) may have devastating consequences.
Hypotension, or low-flow states, must be avoided at all costs. A prophylactic intervention is maintenance of adequate hydration. Accurate determination of fluid requirements is important, but adherence to that administration schedule is essential.
Bleeding times and platelet function must be determined preoperatively. The elevated adhesiveness of the patient’s platelets, which increases the risk of thrombus formation, warrants the administration of low-dose aspirin or dipyridamole as a counteraction. Antiembolic stockings and/or sequential pneumatic compression devices should be used as prophylaxis against venous stasis and potential deep vein thrombosis.
The patient with homocystinuria is susceptible to hypoglycemia secondary to hyperinsulinemia, which is triggered by hypermethionemia. Capillary blood glucose should be monitored, typically on an hourly basis, throughout the perioperative period. It may be prudent to include glucose-containing solutions in the fluid replacement regimen.
The patient with osteoporosis requires extra care when being positioned to avoid undue trauma or injury. If possible or feasible, allow the patient to position himself or herself for comfort and safety.
For general anesthesia, the maintenance agent selected should promote high peripheral flow, reduce vascular resistance, maintain cardiac output, and allow for rapid recovery. Regional anesthesia may be employed, but particular attention should be paid to preparatory fluid loading to avoid hypotension resulting from the induced sympathectomy of the regional anesthetic. Instillation of the regional anesthetic may be challenging, particularly in the patient with kyphoscoliosis.
The patient with both kyphoscoliosis and pectus excavatum may demonstrate a pattern of restrictive lung disease. Direct laryngoscopy may be difficult because of the skeletal defects similar to those of Marfan syndrome (p. 216) that may be produced by homocystinuria.
