Classic homocystinuria due to cystationine beta synthase deficiency is an autosomal recessive disease that affects 1 to 9 of every 100,000 newborns, but is detected in only 1 of every 344,000. In recent years, the incidence of this disease is rising notably, causing that in some areas of the planet it is found in 1 in every 20,000 children. This important increase is causing the number of studies that are carried out on this disease to be increasing notably. The first investigations published in PubMed date back to 1963, with 3 articles while, today, more than 80 research articles are published per year, the most recent being on the use of liver transplantation as an effective treatment in patients with classic homocystinuria , or on obsessive-compulsive behaviors in these patients as a pathognomonic manifestation.

The disease is diagnosed through 3 types of tests:

  1. Analysis of amino acids in blood, including total homocysteine.
  2. Evaluation of the enzymatic activity of the CBS enzyme.
  3. Screening for mutations in the CBS gene (21q22.3).

The characteristics that these patients present are:

  1. Ocular system: ectopia lentis and severe myopia.
  2. Musculoskeletal system: genu valgum, pes cavus, dolicostenomelia, pectus excavatum or carinatum, kyphosis or scoliosis, and osteoporosis.
  3. Nervous system: psychiatric disorders, such as obsessive-compulsive disorder, have been detected in 51% of patients. They also have mental retardation that does not usually appear before 2 years of age.
  4. Cardiovascular system: thromboembolic events that are the cause of death in a large part of patients with this condition.
  5. Others: skin, liver and capillary alterations.

The treatments that exist today for this pathology are of 2 types depending on the type of patient, and it is always recommended that it be diagnosed at birth:

  1. Pyridoxine-responding patients: it is based on the administration in pharmacological doses of vitamin B6, B9 and B12.
  2. Non-responders to pyridoxine: the patient should have a diet low in methionine and rich in cystine, in combination with vitamins B6, B9 and B12. In addition, in 2007, anhydrous betaine received marketing authorization as an orphan drug, which is used to lower homocysteine ​​levels in patients not responding to pyridoxine (vitamin B6).

Effect of vitamins B6, B9 and B12 on homocysteine plasma decrease. https://www.nejm.org/doi/full/10.1056/nejmoa060900

To date, there is only one clinical trial that is recruiting patients in the world. This is the NCT03406611 trial and it proposes using the drug OT-58 as a new system for the enzymatic replacement of CBS. The results are expected for December 2021, and through this blog, we will publish them so that families and patients can know as quickly as possible what the results have been.

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