Classification and goals - HCU

Classical homocystinuria, caused by CBS deficiency can be classified into two groups:

Homocystinuria, pyridoxine responsive
Homocystinuria pyridoxine non-responsive.

CBS deficiency is initially treated with high doses of pyridoxine to test the responsiveness. The level of homocysteine in the pyrodixine responsive group can be (partially) controlled by vitamin B6 (pyridoxine), as pyridoxine can increase residual CBS activity. Approximately 50% of all cases are pyrodixine responsive, but only around 10% of the patients will respond completely on pyridoxine, bringing homocysteine, methionine, and cysteine plasma levels to normal. Responsive patients continue with pharmacological doses of pyridoxine.

Regardless of responsiveness, folate and cobalamine should be added to avoid vitamin depletion and stimulate homocysterine remethylation.

If plasma homocysteine levels do not decrease in response to high doses of pyridoxine, the aim is to reduce plasma methionine and homocysteine levels by a combination of dietary and pharmacological management.

Management goals:³

Reduce or normalize homocysteine concentrations by a restriction of methionine, supply adequate methionine
Supplementation of betaine, B6, B12 and folate
Ensure optimal growth and development
Prevent catabolism
ensure optimal growth and development

References

Baric I, Fowler B. Sulphur amino acids. In; Blau N (ed) Physician’s guide to the diagnosis, treatment and follow-up of inherited metabolic diseases, 2^nd Springer Heidelberg, 2014:33-46
Dixon M, MacDonald A, White F, Stafford J. Disorders of Amino Acid Metabolism, Organic Acidaemias and Urea Cycle Disorders. In: Clinical Paediatric Dietetics. 4^th ed: Shaw V. West Sussex: John Wiley & Sons Limited, 2014:381-525
Thomas JA. Nutrition management of Inherited Metabolic Disorders, Bernstein LE, Helm JR, Rohr F, Editors, Springer International Publishing Switzerland. 2015:149-158.Bernstein
Yap S, Naughten E. Homocystinuria due to cystathionine beta-synthase deficiency in Ireland: 25 years’ experience of a newborn screened and treated population with reference to clinical outcome and biochemical control. J Inherit Metab Dis. 1998;21:738–47.