Fabry disease is a genetic disorder caused by deficiency of the alpha-galactosidase-A enzyme. This leads to the accumulation of a sugar-lipid molecule called Gb3 in various types of cells in the body such as the small blood vessels, nerves, kidneys, and muscles of the heart and brain, damaging the function of these organs.

The disease is related to a gene defect on the X-chromosome, which is one of the sex chromosomes. Despite the fact that they have two X-chromosomes, the disease can also affect women.

Today there are effective treatments for Fabry, so it is very important to be familiar with the symptoms so that more people can be diagnosed at an early stage. Symptoms usually begin appearing in childhood and worsen over time. Some patients suffer from many symptoms involving different systems in the body, while others have a lighter version of the disease and present only some symptoms.

Fabry disease is a multi-systemic disease characterized by a range of symptoms:

Stroke. One of the main complications of Fabry disease are ischemic mini-strokes; these are common among both men and women with the disease and can occur at a young age. There is a high prevalence of stroke even among female carriers.

Pain. Episodes of burning pain, usually in the hands and feet. The pain may pass quickly or last several hours. Patients usually experience the pain if they are exposed to hot or cold heat sources, or if they become hot due to physical activity or emotional distress.  The sensation is similar to the neuropathic pain characteristic of diabetes, and it is resistant to standard painkillers. Other types of pain are also common, often in the large joints.

Impaired kidney function. The first sign of this is the presence of protein in the urine. Over time, the damage to the kidneys can worsen to the point of chronic kidney disease and even kidney failure requiring dialysis or a kidney transplant. 

Skin lesions. Small reddish-black lesions on the skin caused by accumulation of Gb3 in the walls of the small blood vessels, which appear especially in the groin area and multiply over time.

Decreased sweating that can cause increased body temperature and difficulty performing physical activity.

Heat intolerance.

Digestive problems. Prolonged stomach aches and frequent incidents of heartburn (acid reflux) — discomfort caused by stomach acid travelling up to the esophagus, sometimes accompanied by nausea and vomiting. Symptoms that do not respond well to standard antispasmodic, antacid or antidiarrheal medication.

Cardiac symptoms. Cardiac arrhythmias and cardiac conduction system disorders that often cause early symptoms in the second decade of life. In addition, the disease also causes progressive enlargement of the left ventricle of the heart, which can worsen in the case of arterial hypertension.

Vision disorders. Changes in the corneal structure, which can be diagnosed with a vision test using a slit lamp, and clouded vision.

Tinnitus. Ringing in the ears and hearing loss.

Chronic fatigue and psychological distress. Around half of those diagnosed with Fabry disease develop depression, and many experience a decrease in attention span and speed of processing information.

Prevalence of Fabry Disease

The prevalence of Fabry disease is estimated to be one in every 80,000 births, and it can also appear at a later age. The disease is not more common among any specific ethnicity and affects all demographics equally. There are estimated to be around 200 people in Israel with the disease, though only 45 patients have been diagnosed to date, and there are assumed to be many who have not been diagnosed.

Diagnosing Fabry Disease

As the disease is characterized by a wide and varied range of symptoms, and there are differences in the symptoms exhibited by different families that have it, it can be very difficult to detect, and the process of diagnosis may take a long time.

Diagnosing the disease in men is performed by checking the levels of the enzyme in the blood; low levels of the enzyme may indicate the presence of the disease. Checking enzyme levels cannot be used to diagnose the disease in women, and it is usually necessary to sequence the gene encoding the alpha-galactosidase-A enzyme.

The diagnostic process includes differential diagnosis for medical conditions that may lead to similar symptoms, such as growing pains in children, pain caused by rheumatoid arthritis, and multiple sclerosis.

Patients are generally referred for an MRI, where changes in the composition of white matter in the brain are usually detected. White matter disease, a characteristic manifestation of blood vessels with a small diameter, begins at a younger age in Fabry patients than in people with other diseases.

Treatment

Fabry disease is a multi-systemic disease that requires a comprehensive approach to treatment. The medical recommendation is to begin treatment as early as possible to avoid complications and irreversible damage to the body’s tissues. The most important development in treating Fabry disease is enzyme replacement therapy (ERT), which can improve the patient’s condition and prevent irreversible tissue deterioration.

Two ERT drugs have been developed: Replagal and Fabrazyme. Various studies have shown both medications to be effective in maintaining kidney function, reducing pain, and improving heart health.

Both treatments are administered intravenously at a clinic every two weeks — Fabrazyme for a duration of around three hours and Repalgel for a duration of 40 minutes.

An alternative approach is “substrate reduction” therapy with a drug sold in Israel under the name Galafold, which is suitable only for special mutations of the disease.

In the framework of in vitro fertilization, preimplantation genetic diagnosis (PGD) may be performed to select embryos that do not carry the mutation in the gene encoding the alpha-galactosidase enzyme, thus preventing hereditary transmission of the disease.

As Fabry disease is progressive and worsens gradually, those diagnosed with it must adhere to a lifestyle that involves numerous periodic medical tests, including general blood and urine tests, kidney function tests, blood tests for thyroid function, ECG, echocardiography, MRI, CT, and hearing and vision tests. 

Find more details on Takeda Israel‘s website.