[A case report of pyridoxine-responsive homocystinuria]

Homocystinuria is a rare, congenital, autosomal-recessive, metabolic disease biochemically characterized by homocysteinemia and homocystinuria and by multi-system clinical disorders. It is a biochemical abnormality of methionine metabolism caused either by transulfuration pathway disorders or by disorders of homocysteine remethilation into methionine and as such it can be a result of numerous specific and different genetic lesions.

Homocystinuria is most commonly caused by deficiency of cystationine beta synthetase enzyme which catalyses the synthesis of cystathionine from homocysteine and serine in the methinione pathway. This results in accumulation of homocysteine and methionine in plasma and leads to excretion of excessive urinary homocysteine. Depending on specific property of the mutant enzyme molecule some patients respond to very high doses of pyridoxine with decreases of methionine and homocystine and some not. Pyridoxine responsiveness is based on the presence of small residual activity of cystathionine beta synthetase which is not present in nonresponsive patients. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is characterized by numerous different clinical abnormalities, but changes in four organ systems are dominant (eye, skeletal, central nervous and vascular system).

Six years ago a six year-old boy was admitted to the hospital with vision problems. Ophthalmologic examination revealed a lens dislocation and because of many stigmates the child was sent to endocrinologist. The child had a marfanoid stature, with pectus carinatum and genu valgum, ataxic gait with motoric discoordination, muscle tone which ranged from hypotonia to hypertonia of extrapvramidal type and low intellectual abilities. A simple cyanide-nitroprusside test of patient's urine was positive suggesting homocystinuria. The diagnosis was established after plasma and urine amino acid analysis by HPLC. Concentration of homocystine and methionine were 52 mumol/l and 57 mumol/l in plasma and 249 mumol/du and 55 mumol/du in urine, respectively. After four months of treatment with pyridoxine there were not any significant changes in plasma homocysteine and methionine, but at the same time decrease in urine of these two amino acids were more than 2.5 times higher. This confirms that the patient has a pyridoxine-responsive type of homocystinuria and the dose was increased to 60 mg/day and 600 mg/day. This results in further decline of homocysteine and methionine in plasma and urine which persists up to now (for six years).