Vladimír Bzdúch, Katarína Brennerová, Jana Škodová, Anna Krajčovičová, Darina Behúlová
Classical homocystinuria due to cystathionine ß-synthase deficiency is a treatable autosomal recessive disorder of methionine
metabolism mostly presented with Marfan-like phenotype with a worldwide incidence of 1 : 65 000 – 1 : 900 000.
Methionine is an essential amino acid that is broken down to homocysteine, which in turn is converted back to methionine
(remethylation) or degraded to cysteine (transsulphuration). Clinical picture of cystathionine ß-synthase deficiency
is characterized by complications involving the eye (dislocation of the optic lens), skeletal (arachnodactyly, osteoporosis,
scoliosis), vascular (thromboembolism) and central nervous system. Elevated plasma total homocysteine levels are considered
to be the cause of the major clinical manifestations. The first cases of homocystinuria were discovered in 1962 by
Carson and Neill from Ireland. In Slavic population first case was described by professor Hyánek in 1972. Pyridoxine nonresponsive
patients with G307S mutation present earlier and have more severe phenotypes with more complications
than patients with clear response to pyridoxine with I278T mutation. The objective in treating classical homocystinuria
is to reduce the accumulation of homocysteine by low protein, methionine restricted and cystine supplemented diet in
combination with pyridoxine, folic acid and vitamin B12. Important is also increasing rate of homocysteine remetylation
by betaine, especially for patients in whom dietary management is unsatisfactory. Treatment must be started very early
in life to be truly effective, so homocystinuria should be included in the differential diagnosis of psychomotor retardation
and Marfan syndrome or thromboembolism also in adult age. Cystathionine ß-synthase deficiency has generally
been regarded as a rare disease, but new data found by molecular screening show its higher incidence.