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Homocystinuria: a commentary
  1. Aidan Ryan1,2,
  2. Patrick J Twomey3,4
  1. 1 Chemical Pathology, Cork University Hospital Biochemistry Laboratory, Cork, Ireland
  2. 2 Pathology, University College Cork College of Medicine and Health, Cork, Ireland
  3. 3 Clinical Chemistry, St Vincent's University Hospital, Dublin, Ireland
  4. 4 University College Dublin School of Medicine and Medical Science, Dublin, Ireland
  1. Correspondence to Dr Aidan Ryan, Chemical Pathology, Cork University Hospital Biochemistry Laboratory, Cork, Ireland; aidan.ryan1{at}hse.ie

https://doi.org/10.1136/jcp-2022-208606

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    Homocysteine (HCY) is a non-essential sulfur containing amino acid under normal circumstances is converted into cysteine (transulfuration pathway) or remethylated (remethylation pathway) forming methionine. Three HCY fractions exist with, 70% albumin bound, 30% oxidised (HCY can be conjugated to another molecule of HCY by disulfide bonding to form homocystine) and free HCY is usually only a trace.1 While free HCY is pathogenic, it is difficult to measure, is unstable and is an insensitive marker as it only becomes detectable when total-HCY (tHCY) is above 50–60 µmol/L(90% CI 15 to 100 µmol/L).2 3 Hence tHCY in plasma is measured and preferred.

    Measurement of urinary HCY is also insensitive as it only becomes detectable once plasma tHCY exceed approximately 150 µmol/L.2 Historically the first cases were described in 1962, like many other amino acid disorders at the time, used urine samples with a ninhydrin based chromatography method.4 Methods then had analytically (and thus clinically) low sensitivity and were only suitable to detect homozygotes with classical homocystinuria. This was, due in part to the fact that the amino acid analyzers used, measured acid soluble cysteine-HCY mixed disulfide only.5 Developments in assays particularly in HPLC (high-performance liquid chromatography) made it possible to measure the lower tHCY concentrations in plasma.

    A standard reference material6 is available for HCY and although not widely available, reference standard methods also exist, namely GC-MS (gas chromatography-mass spectrometry) and liquid chromatography-mass spectrometry.6 7 Historically, HPLC methods with more manual processing were more widespread; however, developments in fluorescence polarisation immunoassay have simplified the analysis without sacrificing in quality of patient results when compared with the reference method.8 Such immunoassays are available on automated random access immunoassay analysers, which increases the availability of HCY to less specialist laboratories as well as potentially decreasing the …

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    Footnotes

    • Handling editor Tahir S Pillay.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Commissioned; internally peer reviewed.

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