LabMed

Cystathionuria

At a Glance

Cystathionuria is an inherited deficiency in the enzyme γ-cystathionase (CTH, also known as cystathionine gamma-lyase). This enzyme is a part of the sulfur-containing amino acid metabolism, including methionine, homocysteine (HCY), and cysteine. Defects in CTH activity result in elevations of cystionine that can be detected in plasma and urine.

Cystathionuria is inherited in an autosomal recessive manner. Autosomal recessive inheritance means the individual inherited two abnormal copies of the CTH gene (each gene containing a mutation). Both parents of an individual with cystathionuria are carriers and do not manifest any symptoms of disease.

Most individuals with cystathionuria are asymptomatic. Some reports of individuals with developmental delay have also had healthy siblings and may reflect ascertainment bias.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Cystathione is quantified on plasma and urine amino acid analysis. The normal range may vary, depending on the age of the child.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Cystaionine coelutes near alloisoleucine, and misidentification, although unlikely, should be considered in a symptomatic individual. Alloisoleucine may be diagnostic of Maple Syrup Urine Disease, and careful attention must be given when looking for elevations of leucine, isoleucine, and valine that would indicate this disorder.

Plasma and urine cystathionine levels may be elevated in the first 3 months of life and are higher in infant fed artificial formulas.

Vitamin B6 (pyridoxine) deficiency should also be considered as pyridoxine is an essential cofactor for CTH.

Elevated cystathione may be found in some cobalamin disorders, cystahionine β-synthetase deficiency (see chapter on Homocystinuria), and methionine tetrahydrofolate reductase (MTFHR) deficiency.

What Lab Results Are Absolutely Confirmatory?

As this disorder is not thought to have any clinical significance at this time, no further diagnostic testing is recommended.

Sequencing of the CTH gene for γ-cystathioninase has been done in a research setting.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

There is no testing that would be recommended to further confirm this disorder. As currently there are no known clinical consequences of this disease further testing is not necessary. Some reports have suggested that individuals with mutations may be responsive to pyridoxine therapy, as pyridoxal-5'-phosphate is a required cofactor, but the effect upon the levels of cystathionine or clinical significance of this is unclear.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Elevations of cystathione on urine amino acids may be nonspecific, and repeat analysis with plasma amino acids should be performed. Urine samples may also have low creatinine levels and cause artificial elevations in cystathionine and other amino acids.

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