Homozygous Familial Hypercholesterolemia: the story of Valentina.

I have been getting treatment since I was 1 year old. September 24th is World Familial Hyper cholesterolemia Day, a blood disease. Do you know what it is? Here is our in-depth analysis of the patient’s testimony. Valentina is 29 years old and is a critical care nurse. She discovered she had homozygous familial hypercholesterolemia at about the age of 1 year.

The first alarm bell was the appearance of orange spots (xanthomas) on the body. In particular, on the elbows, knees and the back of the thighs – says Valentina. My parents, worried, immediately turned to the paediatrician who, having doubts about the possible cause, advised us to consult a dermatologist. Once we arrived at a specialised dermatology clinic, the head doctor immediately asked if there were any cases of hypercholesterolemia in the family (my parents are both heterozygous hypercholesterolemia), and from there, all the genetic tests and complete blood count tests began, which led to my diagnosis of hypercholesterolemia homozygous familial.

How did you take this news?

Initially, I was too young to be aware of the situation; I don’t have many memories of the first five years of life. I’m starting to remember when the Policlinico Umberto took me to Rome to carry out plasmapheresis sessions at age five. The first time I took the Milan-Rome journey, taking the train and travelling made me feel lucky. But I no longer liked travelling when I started understanding why I had gone to Rome.

What impact did the illness have on a physical and psychological level?

My mother tells me that she often dressed me in clothes that could cover the xanthomas, even in summer. Because many mothers asked her what I had and were sceptical about letting their children play with me, thinking it was a contagious disease. Since the discovery of my pathology, I have been prescribed a diet free from animal fats, sweets, and fried foods. At nursery school, I was the only child who didn’t stop in the canteen for lunch but went home. School, especially in elementary and middle school,  was most affected by my trips to Rome.

For example, I only took part in the class photo for several years because it was always taken on Thursdays, the day I was in therapy. For the same reason, I often had to give up school trips because they were close to or coincided with the day I had to be at the Polyclinic for plasmapheresis.

How did you deal with therapy?

Shortly before the age of five, I started treatment with plasmapheresis at the Umberto I hospital in Rome. The sessions were every two weeks. In 2006, when I was 15, after a year, they were no longer able to do plasma exchange due to difficult access to my veins, and they gave me a fistula. At that point, my mother tried to arrange for me to be treated in Milan, even though I was not yet an adult. At that time, plasmapheresis in Lombardy was only for adult patients. Fortunately, my mother could have me taken care of at a centre in Milan, the Niguarda Hospital in Milan. After about a year of plasmapheresis at Niguarda, the fistula closed.

For this reason, the doctors suggested that I try drug therapy. I started therapy with a drug that was not available in Italy at the time, ezetimibe. My mother and brother went to Switzerland to take it. This, fortunately, allowed me to keep my values under control. In the meantime, every two years, I went to Rome to have a control coronary angiography. To make sure that I had no possible complications due to hypercholesterolemia. The real turning point, however, came a few months before I turned 18. The doctors at Niguarda told me about a trial on an oral drug that had just ended in America and which had given very positive results.

Endless Testing

The experimentation would have started in Italy shortly after, and I could have been a viable candidate. Once I turned 18, I signed the consent to participate in the trial and started treatment with this new therapy. With the new oral therapy in capsules, I reached blood cholesterol levels I had never reached. I did not exceed 100 mg/ml. Furthermore, I was lucky enough to tolerate the drug very well without having any particular side effects. I have been getting treatment with this drug for 10 years. Once the trial ended in 2019, the Lombardy Region struggled to find the drug.

Therefore, the oral therapy in capsules was replaced with another drug. However, it did not give the same results in terms of values and had the most unfavourable and annoying method of administration (three subcutaneous injections every 15 days). In 2020, thanks to the COVID-19 health emergency, travel and access to Niguarda became more difficult. I looked for another centre in Lombardy that treated hypercholesterolemia closer to home. Furthermore, I wanted to restart treatment with oral capsule therapy. I, therefore, turned to the Bassini Hospital in Cinisello Balsamo, which agreed to take care of me. So, after having redone the necessary checks and completed the blood count test, I was able to start oral therapy again. I took a lower dosage than two years ago, but the values have returned to being very good.

How are you today?

Today, I can lead a normal life without any particular sacrifice. I can carry out any work or leisure activity, and I don’t have too many restrictions in terms of nutrition. When I talk about hypercholesterolemia, people often think that it is “simply” high cholesterol and tend to belittle it. They hardly know the homozygous pathology and all its consequences.

Have you ever contacted patient associations? Which?

When I was treated at the Policlinico Umberto I in Rome, ANIF (National Familial Hypercholesterolemia Association) was founded. Of which my mother was vice-president. I recently became aware of the GIP-FH (Italian Familial Hypercholesterolemia Patients Group), which I know carries out information activities on the pathology and offers useful services to patients. Furthermore, he is now promoting an initiative to raise disease awareness.”

What message would you like to send to people regarding this pathology?

I suggest to patients with homozygous familial hypercholesterolemia never underestimate any symptom and to be constant in therapy and attentive to possible complications. Today, living with this pathology is possible. With the therapeutic approaches of the past, it was more difficult. Therapies have been taking giant strides. Today, many options are available to live with a good quality of life.

The important thing is to recognise the pathology, have the appropriate pharmacological tools and act as soon as possible! The homozygous form (HoFH), however, is characterised by the onset of cardiovascular diseases even at a young age and by the presence of characteristic accumulations of fat such as xanthomas (yellowish nodules on the knuckles of the hands and the Achilles tendon) and yellowish on the eyelids and around the eyes). The genetic defect is inherited from both parents, and the risk of heart attack in the absence of therapy is already observed around 15-20 years of age.

The condition

In fact, in this condition, the liver cannot metabolise the lipoproteins that remain in the blood and accumulate. This leads to the dysfunctions already illustrated and creates a situation incompatible with life. It should be noted that cholesterol, usually demonised, is instead a very important component of lipids for life because it is used for the formation of cell membranes (to ensure their function) and protects neurons and cranial nerves. Cholesterol can also synthesise other molecules, including bile acids (important for digestion), some hormones, and Vitamin D. Only if it is present more than these needs can it cause serious damage.

In the case of hypercholesterolemia, cholesterol accumulates in the blood in the form of light lipoproteins (LDL), particular aggregates of fats and proteins, also called “bad cholesterol”, which favour the formation of plaques in the walls of the arteries (atherosclerotic plaques). This happens when patients have such high cholesterol levels that they cannot eliminate it through the physiological mechanisms of the liver. The accumulation of LDL in the blood eventually leads to atheroma formation. That is a physical obstruction to the normal flow of blood. This can lead to the most serious consequences, such as angina, heart attack, and stroke, in the heart, but also in other organs such as the brain, kidneys, lungs and the liver itself.