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A rationale for cystine supplementation in severe homocystinuria

  • Original Article
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Journal of Inherited Metabolic Disease

Summary

Previous studies have shown that the thiol redox, as measured by the ratio of free/bound cyst(e)ine in unaffected individuals, remains relatively constant. In severe homocystinuria (HCU) where cyst(e)ine moieties are significantly reduced, this redox is only restored when homocyst(e)ine moieties are also taken into account. This appears to stem from an increase in the free/bound homocyst(e)ine ratio with free homocystine acting as a surrogate for free cystine. We examined these ratios in 47 patients (two with a cobalamin C defect, two with methylenetetrahydrofolate reductase deficiency, 16 with pyridoxine-responsive HCU and 27 with pyridoxine-nonresponsive HCU). Comparing free/bound homocyst(e)ine ratios to the total cysteine concentration indicates a relative increase of free homocystine as total cysteine concentrations fall below 170 μmol/L. This provides a rationale and treatment algorithm for cyst(e)ine supplementation in homocystinuria.

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Abbreviations

CblC:

cobalamin C

CBS:

cystathionine β-synthase (EC 4.2.1.22)

DTT:

dithiothreitol

HCU:

homocystinuria (from CBS deficiency, OMIM 236200 from MTHFR deficiency, OMIM 236250, from CblC defect, OMIM 277400)

MDS:

cysteine–homocysteine mixed disulfide

MTHFR:

methylenetetrahydrofolate reductase (EC 1.1.1.68)

tCys:

total reduced cysteine accrued from free cystine, mixed disulfide and protein-bound forms

tHcy:

total reduced homocysteine accrued from free homocystine, mixed disulfide and protein-bound forms

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Authors and Affiliations

  1. Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK

    P. J. Lee

  2. Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK

    A. Briddon

Authors
  1. P. J. Lee
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  2. A. Briddon
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Corresponding author

Correspondence to A. Briddon.

Additional information

Communicating editor: Brian Fowler

Competing interests: None declared

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Lee, P.J., Briddon, A. A rationale for cystine supplementation in severe homocystinuria. J Inherit Metab Dis 30, 35–38 (2007). https://doi.org/10.1007/s10545-006-0452-3

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  • DOI: https://doi.org/10.1007/s10545-006-0452-3

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