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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Medical Genetics

Biology & Differential Diagnosis: Why Do You Have Cystathioninuria?

At a Glance

Cystathioninuria is typically a harmless genetic condition caused by a deficiency in the CTH enzyme, leading to a build-up of cystathionine. Doctors run follow-up tests to rule out dangerous conditions like homocystinuria or secondary causes like Vitamin B6 deficiency or liver disease.

To understand why you have cystathioninuria (excess cystathionine in the urine), it helps to look at the “assembly line” your body uses to process proteins. This assembly line is called the transsulfuration pathway [1].

The Assembly Line: How Your Body Processes Proteins

Your body takes an amino acid from your food called methionine and turns it into other substances your body needs [1]. Think of it as a four-step process:

  1. Methionine is converted into Homocysteine.
  2. Homocysteine is converted into Cystathionine.
  3. Cystathionine is converted into Cysteine (used for antioxidants and skin/hair).
  4. Cysteine is used or cleared by the body.

Where the “Block” Happens

In a healthy person, enzymes (special proteins that act as workers) move the process along. If one of these “workers” is missing or not working, the assembly line gets backed up [1][2].

Primary Cystathioninuria (The “Safe” Block)

In primary cystathioninuria, the worker at Step 3 is missing or slow. This worker is an enzyme called cystathionine gamma-lyase (also called CTH or CSE) [3][4].

Because the worker at Step 3 isn’t there to turn cystathionine into cysteine, the cystathionine builds up [5]. However, because the earlier steps (Steps 1 and 2) are still working, your levels of methionine and homocysteine usually stay normal [5]. This is why primary cystathioninuria is generally considered harmless—it’s just a “pile-up” of a non-toxic substance [6].

Homocystinuria (The “Dangerous” Block)

It is crucial for doctors to make sure you do not have homocystinuria. In that condition, the block happens earlier, at Step 2, because of a deficiency in an enzyme called cystathionine beta-synthase (CBS) [7][8].

A block at the CBS step causes homocysteine to build up to very high levels [7]. Unlike cystathionine, high levels of homocysteine are toxic and can cause serious health problems, such as blood clots, eye issues, and intellectual disabilities [9][10]. This is why your doctor will check your homocysteine levels—to make sure the “back-up” isn’t at that dangerous earlier step [6].

Other Reasons for High Cystathionine (Secondary Causes)

Sometimes, the CTH enzyme is perfectly fine genetically, but something else is interfering with it. These are called secondary causes, and they are the main reasons doctors do follow-up tests:

  • Vitamin B6 Deficiency: The CTH enzyme cannot work without Vitamin B6 (its “fuel”). A mild deficiency can cause a “safe block,” leading only to high cystathionine [11]. However, severe B6 deficiency can eventually affect the CBS enzyme (Step 2) as well, which is why doctors check the full panel of amino acids [12][10].
  • Liver Disease: Most of this protein processing happens in the liver. If the liver is damaged or diseased, it may struggle to keep the assembly line moving [13][14].
  • Specific Pediatric Tumors: In very rare cases, mostly in infants and young children, a type of pediatric cancer called neuroblastoma can produce extra cystathionine [15][16]. If you are an adult researching your lab results, this is exceedingly unlikely to apply to you. Even in children, it is a secondary check rather than the most likely answer.

Why Differentiation is the Goal

When a doctor sees high cystathionine, their main goal is a differential diagnosis—meaning they want to rule out the dangerous things (like homocystinuria) or treatable things (like a vitamin deficiency) [6]. If they confirm your homocysteine is normal and your liver is healthy, the most likely answer is that you simply have a harmless genetic variation in your CTH enzyme [6].

Common questions in this guide

What causes primary cystathioninuria?
Primary cystathioninuria is caused by a genetic deficiency or slowness in an enzyme called cystathionine gamma-lyase (CTH). This missing or slow enzyme causes a harmless build-up of cystathionine in the body.
What is the difference between cystathioninuria and homocystinuria?
Cystathioninuria is usually a harmless build-up of cystathionine due to a block late in your body's protein processing. Homocystinuria is a dangerous condition where an earlier block causes toxic levels of homocysteine to build up, potentially leading to blood clots and other serious issues.
Why does my doctor check my homocysteine and methionine levels?
Doctors check these levels to completely rule out homocystinuria. If your homocysteine and methionine levels are normal, it usually confirms that your enzyme block is at a safe step and you only have a harmless cystathionine build-up.
Can a vitamin deficiency cause high cystathionine?
Yes, a deficiency in Vitamin B6 can cause cystathionine levels to rise. The enzyme responsible for clearing cystathionine relies on Vitamin B6 for fuel, so low levels of this vitamin can create a temporary block in your metabolic pathway.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Are my homocysteine and methionine levels normal? (This helps confirm it is not homocystinuria).
  2. 2.Do you suspect my cystathioninuria is 'primary' (genetic) or 'secondary' (caused by something else like a vitamin deficiency)?
  3. 3.Should we check my Vitamin B6 levels to see if that is contributing to the high cystathionine?
  4. 4.Are there any signs of liver issues or other health conditions that could be causing this metabolic finding?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (16)
  1. 1

    Endogenous hydrogen sulfide regulates xCT stability through persulfidation of OTUB1 at cysteine 91 in colon cancer cells.

    Chen S, Bu D, Zhu J, et al.

    Neoplasia (New York, N.Y.) 2021; (23(5)):461-472 doi:10.1016/j.neo.2021.03.009.

    PMID: 33878705
  2. 2

    Cystathionine β-synthase is involved in cysteine biosynthesis and H2S generation in Toxoplasma gondii.

    Conter C, Fruncillo S, Fernández-Rodríguez C, et al.

    Scientific reports 2020; (10(1)):14657 doi:10.1038/s41598-020-71469-x.

    PMID: 32887901
  3. 3

    High protein diet-induced metabolic changes are transcriptionally regulated via KLF15-dependent and independent pathways.

    Mehrazad Saber Z, Takeuchi Y, Sawada Y, et al.

    Biochemical and biophysical research communications 2021; (582()):35-42 doi:10.1016/j.bbrc.2021.10.027.

    PMID: 34688045
  4. 4

    Multi-omic screening of invasive GBM cells in engineered biomaterials and patient biopsies reveals targetable transsulfuration pathway alterations.

    Garcia JH, Akins EA, Jain S, et al.

    bioRxiv : the preprint server for biology 2023; doi:10.1101/2023.02.23.529575.

    PMID: 36865128
  5. 5

    Abnormal Amino Acid Profiles of Blood and Cerebrospinal Fluid from Cystathionine β-Synthase-Deficient Mice, an Animal Model of Homocystinuria.

    Akahoshi N, Yokoyama A, Nagata T, et al.

    Biological & pharmaceutical bulletin 2019; (42(6)):1054-1057 doi:10.1248/bpb.b19-00127.

    PMID: 31155583
  6. 6

    Potential Misdiagnosis of Hyperhomocysteinemia due to Cystathionine Beta-Synthase Deficiency During Pregnancy.

    Stabler SP, Freehauf C, Allen RH, et al.

    JIMD reports 2017; (37()):55-61 doi:10.1007/8904_2017_15.

    PMID: 28275971
  7. 7

    Enzyme replacement with PEGylated cystathionine β-synthase ameliorates homocystinuria in murine model.

    Bublil EM, Majtan T, Park I, et al.

    The Journal of clinical investigation 2016; (126(6)):2372-84.

    PMID: 27183385
  8. 8

    Real-time detection of enzymatically formed hydrogen sulfide by pathogenic variants of cystathionine beta-synthase using hemoglobin I of Lucina pectinata as a biosensor.

    Myszkowska J, Klotz K, Leandro P, et al.

    Free radical biology & medicine 2024; (223()):281-295 doi:10.1016/j.freeradbiomed.2024.07.031.

    PMID: 39067625
  9. 9

    Proteomic exploration of cystathionine β-synthase deficiency: implications for the clinic.

    Jakubowski H

    Expert review of proteomics 2020; (17(10)):751-765 doi:10.1080/14789450.2020.1865160.

    PMID: 33320032
  10. 10

    Cystathionine β-Synthase Deficiency in the E-HOD Registry-Part II: Dietary and Pharmacological Treatment.

    Morris AAM, Sokolová J, Pavlíková M, et al.

    Journal of inherited metabolic disease 2025; (48(1)):e12844 doi:10.1002/jimd.12844.

    PMID: 40095936
  11. 11

    On pathways and blind alleys-The importance of biomarkers in vitamin B6 -dependent epilepsies.

    Plecko B

    Journal of inherited metabolic disease 2023; (46(5)):839-847 doi:10.1002/jimd.12655.

    PMID: 37428623
  12. 12

    Elevated plasma cystathionine is associated with increased risk of mortality among patients with suspected or established coronary heart disease.

    Dhar I, Lysne V, Svingen GFT, et al.

    The American journal of clinical nutrition 2019; (109(6)):1546-1554 doi:10.1093/ajcn/nqy391.

    PMID: 31005968
  13. 13

    The Role of the Transsulfuration Pathway in Non-Alcoholic Fatty Liver Disease.

    Werge MP, McCann A, Galsgaard ED, et al.

    Journal of clinical medicine 2021; (10(5)) doi:10.3390/jcm10051081.

    PMID: 33807699
  14. 14

    Role of H2S in Regulation of Vascular Tone in Metabolic Disorders.

    Birulina YG, Ivanov VV, Buyko EE, et al.

    Bulletin of experimental biology and medicine 2021; (171(4)):431-434 doi:10.1007/s10517-021-05243-y.

    PMID: 34542747
  15. 15

    Hydrogen sulfide modulates epithelial-mesenchymal transition and angiogenesis in non-small cell lung cancer via HIF-1α activation.

    Wang M, Yan J, Cao X, et al.

    Biochemical pharmacology 2020; (172()):113775 doi:10.1016/j.bcp.2019.113775.

    PMID: 31870768
  16. 16

    Sulfurtransferases and Cystathionine Beta-Synthase Expression in Different Human Leukemia Cell Lines.

    Jurkowska H, Wróbel M, Jasek-Gajda E, Rydz L

    Biomolecules 2022; (12(2)) doi:10.3390/biom12020148.

    PMID: 35204649

This page explains the biology and diagnosis of cystathioninuria for educational purposes only. Always consult your healthcare provider or a genetic specialist to interpret your specific metabolic lab results.

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