Classical
homocystinuria is a hereditary defect of the
enzyme cystathionine beta synthase, which is produced in the liver. If this
enzyme fails, the synthesis pathway of
cysteine from
methionine is interrupted, leading to the accumulation of
homocysteine in the blood plasma and
homocysteine in the urine. After birth, the children are unremarkable except for the characteristic laboratory findings. Symptoms rarely appear before the second year of life. The most common symptom is a
prolapse of the crystalline lens. This finding is seen in 70% of untreated 10-year-old affected individuals. As the earliest symptom, psychomotor retardation occurs in the majority of patients already during the first two years of life. Limiting factors in terms of life expectancy are
thromboembolism,
peripheral arterial disease,
myocardial infarction, and
stroke. These symptoms are due to the damage to the vessels caused by the elevated
amino acid levels. About 30% suffer a thromboembolic event by the age of 20, about half by the age of 30. This review focus on present and new therapeutical approaches like the role of
enzyme replacement with presentation of different novel targets in research like pegtibatinase, pegtarviliase, CDX-6512, erymethionase, chaperones,
proteasome inhibitors and probiotic treatment with SYNB 1353. Furthermore, we analyze the role of liver-directed
therapy with three dimensional (3D) bioprinting, liver bioengineering of liver organoids in vitro and
liver transplantation. The role of different gene therapy options to treat and cure this extremely
rare disease in childhood will be discussed.