Diet principles - HCU

Dietary management is based, as in most disorders of amino acid metabolism, on decreasing the load of the affected pathway and supplementing deficient products beyond the metabolic block.

Primary aim of dietary management is to correct abnormal biochemistry, especially to control elevated plasma homocystine concentrations as much as possible to prevent or at least reduce the complications of homocystinuria and to prevent further complications such as thrombosis³. In those who have already had a vascular event, betaine therapy alone may prevent recurrent events.⁴

reduce plasma methionine levels to within or slightly above the normal age related reference range unless on betaine therapy,
decrease plasma homocysteine levels and increase plasma cysteine levels to within the normal range.
Ensure optimal growth and development

Management strategies aim at reducing homocysteine levels by:

Decreasing the intake of methionine by a protein restricted diet to reduce plasma methionine levels and thereby homocysteine levels
Giving additional pharmacological dose of folic acid, 5 mg daily, to ensure adequate supply of folate for remethylation pathway
Utilising alternative pathways to remove homocysteine by giving betaine, which reduces plasma homocysteine levels.

Management choices are made based on factors like age and mode of diagnosis, ie clinically or Newborn screening (NBS) diagnosed. Those diagnosed through NBS are most likely to be solely managed by diet, at least in the early years, than those clinically presenting at a later age.

The diet for HCU patients must be individualized depending on each patient’s nutrient and growth requirements. The amount of natural protein allowed in the diet depends on the patient’s residual enzyme activity and growth velocity. Tolerance varies from one patient to another; it will be influenced by growth rate and anabolism. Close monitoring is essential.

A L-amino acid supplement that contains no methionine but does contain all the remaining amino acids and has added vitamins, minerals and trace elements can be used to supplement natural protein intake and ensure normal growth. This supplement should contain an adequate level of cysteine, as cysteine is normally formed from methionine, intake of which is limited in these patients^2,5.

Diet principles^1,2

Limit the intake of natural protein to maintain plasma methionine and homocysteine concentration within the desired range.
Ensuring an adequate amount of natural protein to support normal growth and development but also to maintain blood levels within the desired range.
Adequate L-amino acid supplementation by a methionine-free protein substitute, enriched with cysteine and micronutrients, essential fatty acids up to a level recommended in the age range, in order to maintain adequate protein status for HCU patients.
Adequate energy intake to promote appropriate growth and weight maintenance and prevent catabolism.
Monitor nutritional status and adjust diet as needed.
Provision of a palatable, varied and ‘easy to maintain’ diet.
Provision of an emergency regimen during illness, fasting and infections, surgery or increased activity

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: 19914636
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.
Lawson-Yuen A, Levy HL. A betaine treatment for the homocystinurias. In: Theone J, ed. Small Molecule Therapy for Genetic Disease. New York, NY: Cambridge University Press; 2010:173-81.
Generosa, A., B. Fowler, and G. Sebastio, Disorders of sulfer amino acid metabolism, in Inborn Metabolic Diseases, J.-M. Saudubray, van den Berghe, G and Walter, J. H., Editor. 2012, Springer-Verlag: Berlin. p. 311-321.