Homocystinuria laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayokunle Olubaniyi, M.B,B.S [2]
Overview
Laboratory Findings
The term homocystinuria describes an increased excretion of the thiol amino acid homocystine in urine (and incidentally, also an increased concentration in plasma). The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency. Others include the re-methylation defects (cobalamin defects, methionine sythase deficiency, MTHFR) and vitamin deficiencies (cobalamin (vitamin B12) deficiency, folate (vitamin B9) deficiency, riboflavin deficiency (vitamin B2), pyridoxal phosphate deficiency (vitamin B6)). In light of this information, a combined approach to laboratory diagnosis is required to reach a differential diagnosis.
CBS deficiency may be diagnosed by routine metabolic biochemistry. In the first instance plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocystine. In fact many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g. MTHFR, methionine synthase deficiency and the cobalamin defects) in lieu of the elevated methionine concentration.[1] Additionally, organic acid analysis and/or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.[2]
The laboatory analysis of homocystine itself is complicated by the fact that most homocystine (possibly >85%) is bound to other thiol amino acids and proteins in the form of disulphides (e.g. cysteine in cystine-homocystine, homocysteine in homocystine-homocystine) via disulphide bonds. Since as an equilibrium process the proportion of free homocystine is variable a true value of total homocysteine (free + bound) is useful for confirming diagnosis and particularly for monitoring of treatment efficacy. To this end it is prudent to perform total homocyst(e)ine analysis in which all disulphide bonds are subject to reduction prior to analysis, traditionally by HPLC after derivatisation with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample.[3]
References
- ↑ (eds.), N. Blau ... (2003). Physician's guide to the laboratory diagnosis of metabolic diseases ; with 270 tables (2. ed. ed.). Berlin [u.a.]: Springer. ISBN 354042542X.
- ↑ Refsum, Helga (2004). "Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion". Clinical Chemistry. 50 (1): 3–32. PMID 14709635. Unknown parameter
|coauthors=ignored (help) - ↑ Carducci, Claudia (1999). "Automated high-performance liquid chromatographic method for the determination of homocysteine in plasma samples". Journal of Chromatography A. 846: 93–100. PMID 10420601. Unknown parameter
|coauthors=ignored (help)