Cavernomas—a patient’s efforts to understand the possible systemic implications of a defect in the Krit1 (CCM1) gene
André Van Sint Feijth is a 64-year-old man from Maastricht in the Netherlands who has experienced poor health for more than 30 years. His discovery in 2013 that he lives with multiple cavernomas was the start of an in-depth exploration of the research literature to see whether his defective Krit1 (also known as CCM1) gene might be responsible for his varied symptoms
André first became aware of problems with his health in 1989. He was working as a tax official when he noticed increasing fatigue. Over the next five years this fatigue became chronic. Staying awake all day became a physical impossibility, and eventually he had no choice but to sleep in the afternoons. He says, “People at work and elsewhere didn’t believe that. To them I was just a profiteer.” André was saddened to have to take early retirement in 1998.
Chronic fatigue is just one of the many health challenges that André continues to face. He has also contended with genitourinary, gastrointestinal, cardiovascular, ENT, dermatological and other problems.
These many symptoms have varied in their timing and intensity. As André puts it, “they are irregularly regular” and can be very painful. They affect his whole body and that, he says, “makes life not easy, to say the least”, especially when the symptoms overlap. In the past, he took delight in travelling, but now this is impossible.
One of the greatest health challenges for André has been living with dumping syndrome. In this condition, the stomach releases food and drink too quickly and that alters hormone levels and causes intestinal swelling. He was greatly relieved when his suspicions that he had the syndrome were confirmed in 2013.
Earlier that same year, André was worried when he lost parts of his memory. He suspected that there could be a link with the known (but rare) side effects of the antidepressants he was taking, so he requested an MRI scan. He was astonished by the results. The scan found four strawberry-sized cavernomas (one was in the pons, which is part of the brainstem) and 36 smaller ones.
“A cavernoma is a cluster of abnormal blood vessels, usually found in the brain and spinal cord. They are sometimes known as cavernous angiomas, cavernous haemangiomas or cerebral cavernous malformation (CCM). A typical cavernoma looks like a raspberry. It’s filled with blood that flows slowly through vessels that are like caverns.” Source: www.nhs.uk/conditions/cavernoma
André’s neurologist referred him to a geneticist, who confirmed the genetic cause of his cavernomas as a defect in his Krit1 gene. André began to wonder whether this was the root cause of the many and varied symptoms he had been troubled by for so long. André redoubled his research efforts, scouring the online biomedical literature for information. In this he was supported by his buddy and caregiver, Rik, who translated content for him. To date they have read the abstracts or full texts of 2,600 articles on PubMed. Their efforts have brought André to a fascinating understanding of eight functions of the Krit1 gene.
Two of the Krit1 functions are particularly important, André explains: “A 2010 paper describes how the gene is responsible for the removal of combustion products when energy is supplied in the cell by the SOD2 enzyme. This leads to devastating oxidative stress.” Furthermore, he says, “A 2015 paper describes how the gene is also involved in the reuse of certain cell components, such as proteins, for new cell parts.” Therefore, André says, a Krit1 gene defect has metabolic implications for the whole of the body, and this may finally explain the symptoms he has contended with for so long.
André would love to contact people with cavernomas caused by a Krit1 defect who also have wide-ranging symptoms. In the Benelux countries (Belgium, the Netherlands and Luxemburg) there is no platform available specifically for people with cavernomas, but he has been in contact with other organisations, such as Angioma Alliance, Cavernoma Alliance UK, European Cavernoma Alliance and Association sur les Cavernomes Cérébraux
André is hopeful that a paper describing his case might be published in a medical journal. His other hopes for the future include:
- being monitored by a multidisciplinary team
- having regular medical follow-ups
- seeing greater awareness and education around the Krit1 gene
- being able to share his knowledge with the medical profession
“The Krit1 gene (also known as CCM1) provides instructions for making a protein that strengthens the interactions between cells that form blood vessels and limits leakage from the vessels.” Source: medlineplus.gov/genetics/gene/krit1/#resources