Dietary management of classical homocystinuria CBS deficiency Andrew

Dietary management of classical homocystinuria (CBS deficiency) Andrew Morris

Dietary protein Protein synthesis Methionine Homocysteine Pyridoxine CBS • Homocysteine formation is minimised by giving enough methionine for protein synthesis but not much more • This needs a very low-protein diet & supplements of the other amino acids

Dietary treatment of babies Combination of • Special formula that contains – All the normal ingredients except protein – All the amino acids except methionine • Breast milk or normal infant formula – To supply methionine for protein synthesis Proportions of the two are adjusted to optimise blood homocysteine & methionine levels

Dietary treatment of older patients • Small, measured amounts of food containing protein • Methionine-free amino acid mixture • Adequate energy from low protein foods – most fruit & vegetables – synthetic e. g. low-protein bread, biscuits, pasta • Vitamin & mineral supplements (included in most amino acid mixtures) • Adjusted to optimise homocysteine & methionine

Challenges in dietary treatment • Distance to specialist centre Telephone advice & taking blood locally or measuring homocysteine in bloodspots can reduce number of visits • Needle phobia may hamper monitoring Play therapists can help to overcome this • Expense & (relative) unpalatability of supplements & low -protein foods Health insurance & medical food companies should be lobbied over these issues • Restrictions are unpopular leading to poor compliance

Factors contributing to poor compliance • • Diagnosis after infancy Adolescence Attitude of family & friends Personality • Newborn Screening can detect most patients with pyridoxine-unresponsive homocystinuria • Addition of Betaine can help if unable to reach homocysteine targets with diet alone (Betaine alone seldom achieves adequate control)

Dietary protein Protein synthesis Methionine Betaine Homocysteine CBS Side effects of betaine • Taste, fishy odour at high doses • Methionine rises, seldom toxic but keep <1000 umol/l