Iron Man: critical role of CBS in iron homeostasis
Prof Wing Ho Yung (Croucher Fellowship 1990) and his research team at the Chinese University of Hong Kong have discovered that experimental mice with a deficiency in the enzyme “cystathionine β-synthase (CBS)” display hemochromatosis-like symptoms, which means excess iron content in the serum and liver, along with damage to major organs.
The study is published in the international medical journal Hepatology and may provide new directions in diagnosing and treating hemochromatosis patients in future.
CBS is an enzyme produced by the liver and other organs. Congenital mutation in the CBS gene could lead to CBS deficiency, a rare hereditary disease that affects metabolic functions. Patients not treated in infancy may have multisystem disorders such as intellectual disabilities, psychiatric disorders, arterial occlusions and osteoporosis.
CBS misregulation brings numerous negative impacts to brain function but we have very limited knowledge in the underlying mechanism.
This research revealed that CBS is also essential for body iron homeostasis. Researchers studied the iron content in the serum and tissues of experimental mice with normal CBS and experimental mice with CBS deficiency. The physiological and metabolic impact of CBS deficiency, including the interference on erythropoiesis, were studied.
It is evidenced that CBS deficiency could lead to a significant decrease in the body weight of the experimental mice. Their iron level is also higher than those with normal CBS, leading to hemochromatosis-like symptoms like liver damage.
Further analysis showed that CBS deficiency could suppress erythropoiesis and lead to excessive iron retention, resulting in hemochromatosis-like symptoms. However, the condition could be partially reversed when the CBS expression in the affected mice was raised through experimental strategy.
For hemochromatosis patients, excessive build-up of iron in the body often leads to cirrhosis and hence increases the risk of liver cancer. It is possible that the results can lead to new directions in diagnosis and treatment for hemochromatosis.
Aside from hemochromatosis, the study is also useful in understanding diseases related to CBS including intellectual disabilities, and other severe brain problems such as psychiatric or behavioural disorders. It can also provide insights into Down’s syndrome, which is commonly associated with excessive CBS.
To view Prof Yung’s Croucher profile, please click here.