scrag
New Member
Hi all, i didn't know which thread to add to,so i started one.
moderator feel free to move it to another thread if you want to.
Scroll to the bottom to see who this was written by,before reading.
Carbohydrate deficient transferrin (CDT)
and is of no relevance in this case as it causes falsely low CDT results. The Dtype is very rare in Caucasians, with a prevalence of less than one in 10,000,but has been shown to cause falsely raised CDT levels. It is more common inAfricans, in whom studies have shown a prevalence of CD heterozygotes of upto 10%.
c) Carbohydrate deficient glycoprotein syndromes: A group of very raresyndromes has now been identified in which an inherited deficiency of theenzymes that add the sidechains to proteins occurs. To date only around 200cases have been described in the literature. In an affected child there is severemental retardation together with other physical abnormalities and CDT levelsare in the range 50-100%. In heterozygous, or carriers of the disease, CDTlevels are variable but typically are in the range 10-25%.
5) Analytical and biological variation
The analytical variability of the CDT assay in use at King’s College Hospital isapproximately 4-5% C.V. at a CDT concentration of 1.3%. Variation is lower athigher CDT concentrations. Occasionally a subject’s total transferrin concentrationis so low that acceptable reproducibility cannot be obtained. Biological variabilityin CDT in any one individual is low - < 10% in our experience, with the possibleexception of pre-menopausal women as detailed in point 3 above. It is, therefore,advisable to base any conclusions on the drinking status of an individual on at leasttwo emasurements of CDT, two weeks or more apart. Our recommendation is forthree samples at two-weekly intervals, particularly in pre-menopausal women asthis spans at least two different stages of the menstrual cycle.
6) Conclusions
CDT testing for alcohol misuse should not be undertaken in isolation, but should becombined with medical history and examination, appropriate questionnaires andother laboratory parameters e.g. MCV, GGT etc.
Dr Roy Sherwood
Consultant Clinical Scientist and Hon Senior Lecturer in Clinical BiochemistryKing’s College Hospital
Denmark Hill
London SE5 9RS May 2008
moderator feel free to move it to another thread if you want to.
Scroll to the bottom to see who this was written by,before reading.
Carbohydrate deficient transferrin (CDT)
- 1) An explanation of how CDT testing can assess the level of alcoholconsumption.
Transferrin is a protein present in blood the function of which is to transport iron.After its amino acid sequence has been formed transferrin undergoes furthermodification by the addition of carbohydrate (sugar) sidechains. This process isunder the control of two enzyme systems; one which adds the sidechains (glycosyltransferases) and one which removes them (sialidases). In normal subjectstransferrin in the blood has 3-5 of these carbohydrate sidechains. In the 1980s agroup in Sweden observed that in individuals misusing alcohol a higher proportionof the transferrin in the circulation had between 0 and 2 carbohydrate sidechains.This subsequently became known as carbohydrate deficient transferrin or CDT.With current commercial assays for CDT’s in normal subjects who consume littleor no alcohol less than 1.6% of their blood transferrin is in the carbohydratedeficient form. Individuals misusing alcohol typically have a higher proportion oftransferrin as CDT (3-10%). Alcohol appears to have a direct effect on the enzymesystems involved in regulating the transferrin sidechains; it inhibits the enzymesadding the sidechains and stimulates the enzymes removing the sidechains. Theadvantage, therefore, of using CDT in testing for alcohol misuse is it is unaffectedby mild alcohol related liver disease or fatty liver (due to obesity, diabetes etc)which can falsely increase γ-glutamyl transferase (GGT), the enzyme in blood mostcommonly used to indicate excess alcohol consumption. CDT is also unaffected bychronic disease or B12/folate deficiencies which can increase the mean corpuscularvolume (MCV), another blood test used to detect alcohol misuse. Transferrinremains in the circulation for 7 to 14 days and CDT, therefore, can give anindication of alcohol consumption over this period of time, which gives it anadvantage over blood or urine alcohol measurements which only remain elevatedfor 24-48 hours after alcohol consumption.
- 2) All possible/probable explanations for the increase in the CDT level toinclude whether any other factors inflate CDT levels.
Alcohol misuse is the commonest reason for increases in CDT levels. In moststudies of CDT in subjects potentially misusing alcohol the test has 95% specificityi.e. 19 out of 20 times the increased CDT is due to excess alcohol intake. There area number of other causes of a raised CDT as detailed below:
- a) Advanced cholestatic liver disease: In patients whose bile ducts areobstructed or damaged by disease e.g. primary biliary cirrhosis, primarysclerosing cholangitis, gallstones or liver/pancreatic cancer, removal of CDTfrom the blood is reduced leading to raised CDT levels. This can be excludedin the case in question by the normal biochemical liver tests as the diseaseneeds to be severe for there to be an effect on CDT.
- b) Transferrin variants: The normal form of transferrin in blood is the C-type.Two more variants exist: the B- and D- types. The B-type is extremely rare
- a) Advanced cholestatic liver disease: In patients whose bile ducts areobstructed or damaged by disease e.g. primary biliary cirrhosis, primarysclerosing cholangitis, gallstones or liver/pancreatic cancer, removal of CDTfrom the blood is reduced leading to raised CDT levels. This can be excludedin the case in question by the normal biochemical liver tests as the diseaseneeds to be severe for there to be an effect on CDT.
and is of no relevance in this case as it causes falsely low CDT results. The Dtype is very rare in Caucasians, with a prevalence of less than one in 10,000,but has been shown to cause falsely raised CDT levels. It is more common inAfricans, in whom studies have shown a prevalence of CD heterozygotes of upto 10%.
c) Carbohydrate deficient glycoprotein syndromes: A group of very raresyndromes has now been identified in which an inherited deficiency of theenzymes that add the sidechains to proteins occurs. To date only around 200cases have been described in the literature. In an affected child there is severemental retardation together with other physical abnormalities and CDT levelsare in the range 50-100%. In heterozygous, or carriers of the disease, CDTlevels are variable but typically are in the range 10-25%.
- 3) Level of alcohol consumption necessary and over what period toincrease the CDT level to 3.0%.
Typically the level of alcohol intake required to produce a CDT result of 3.0% is100-150 g alcohol/day. This equates to about 5 pints of beer, a bottle of wine or onethird of a bottle of spirits daily. As stated earlier the half-life of transferrin in bloodis 7 - 14 days so excess intake would need to fall within this time period. It isimportant at this stage to add the caveat that the relationship between amount ofalcohol consumed and percent CDT is not as reliable in pre-menopausal womencompared to men or post-menopausal women. It is believed that this is due to thechanges in hormones in the blood during the menstrual cycle or present in oralcontraceptives affecting the enzymes involved in regulating the carbohydratesidechains. There is very little information regarding CDT and HRT (hormonereplacement therapy). Total transferrin concentrations increase throughoutpregnancy reflecting the increased requirement for iron of the developing foetus.Although earlier studies expressing CDT in absolute values demonstrated anincrease in CDT in the third trimester there is no evidence that pregnancy itselfcauses an increase in CDT values when expressed as a percentage of totaltransferrin.
- 4) Can CDT levels be increased by intermittent drinking?
Intermittent or “binge” drinking can increase CDT levels. The extent to which thisoccurs is dependent on the frequency of “binges” and the amount of alcoholconsumed on each occasion. Someone drinking 200-300 g alcohol two days aweek, but abstaining on the other days, could have a CDT level of 1.5-3%.Conversely, someone who only has one “binge” in a 14 day period and does notconsume alcohol for the rest of the time period is unlikely to have a raised CDT, asthe normal transferrin produced on the other 13 days would ‘dilute’ the CDTproduced on the day of drinking.
5) Analytical and biological variation
The analytical variability of the CDT assay in use at King’s College Hospital isapproximately 4-5% C.V. at a CDT concentration of 1.3%. Variation is lower athigher CDT concentrations. Occasionally a subject’s total transferrin concentrationis so low that acceptable reproducibility cannot be obtained. Biological variabilityin CDT in any one individual is low - < 10% in our experience, with the possibleexception of pre-menopausal women as detailed in point 3 above. It is, therefore,advisable to base any conclusions on the drinking status of an individual on at leasttwo emasurements of CDT, two weeks or more apart. Our recommendation is forthree samples at two-weekly intervals, particularly in pre-menopausal women asthis spans at least two different stages of the menstrual cycle.
6) Conclusions
CDT testing for alcohol misuse should not be undertaken in isolation, but should becombined with medical history and examination, appropriate questionnaires andother laboratory parameters e.g. MCV, GGT etc.
Dr Roy Sherwood
Consultant Clinical Scientist and Hon Senior Lecturer in Clinical BiochemistryKing’s College Hospital
Denmark Hill
London SE5 9RS May 2008
