Mysteries of Fabry Disease Discussed at Forum in Tashkent

Family screening can identify up to five additional cases of the disease in one family.[1]. The features of the course and detection of Fabry disease became the topic of discussion at the International Forum on the Diagnosis and Treatment of Orphan Diseases “Commonwealth without Borders” in Tashkent.

In this rare inherited disorder, a mutation in the GLA gene disrupts the production of the enzyme α-galactosidase, which is needed to break down complex fats (glycosphingolipids). Their accumulation in the lysosomes of cells triggers a chain reaction that damages various organs and systems of the body.

Fabry disease contains many mysteries, said Ekaterina Zakharova, doctor of medical sciences Head of the Department of Molecular Mechanisms of Hereditary Metabolic Disorders at the Federal State Budgetary Scientific Institution “Research Center for Medical Genetics”. One of the paradoxes of the disease is that it can occur in women despite the fact that the gene responsible for Fabry disease is located on the X chromosome. X-linked diseases usually occur in men.

Another mystery of the disease lies in the peculiarities of its diagnosis. Thus, the two key tests for determining Fabry disease can have directly opposite meanings depending on the patient’s gender. For example, normal activity of the enzyme α-galactosidase A in men excludes the disease, while in women this result is not always clear. At the same time, a normal concentration of the biomarker globotriaosylsphingosine (lyso-Gb3) is unlikely in the presence of the disease in men, but does not exclude it in women.

The absence of specific symptoms in the early stages of the disease and the peculiarities of diagnosis make screening of relatives of patients with Fabry disease particularly important.

“Family screening can help identify patients at an early or preclinical stage of the disease and change their quality of life. When conducting a genealogical analysis, up to five additional cases of the disease can be identified in one family,”
emphasized Ekaterina Zakharova.

Another effective approach is selective screening, which is carried out in high-risk groups. These include patients with unexplained left ventricular hypertrophy, end-stage renal disease, post-kidney transplant patients, and early stroke (aged 15–55 years).

Early diagnosis allows timely administration of enzyme replacement therapy and delays severe complications of the disease. Therefore, it is also necessary to screen children who have certain symptoms.

According to Nato Vashakmadze, doctor of medical sciences, Professor of the Department of Faculty Pediatrics of the Institute of Maternal and Child Health of the Federal State Budgetary Educational Institution of Higher Education “N.I. Pirogov Russian National Research Medical University” Head of the Department of Orphan Diseases and Prevention of Disabling Diseases of the Institute of Pediatrics and Children’s Health of the Scientific and Clinical Center No. 2 of the Federal State Budgetary Scientific Institution “Russian Scientific Center of Surgery named after Acad. B.V. Petrovsky”, a very important manifestation, which is experienced by up to 80% of patients[2] — neuropathic pain in the arms and legs, mainly in the palms and soles of the feet — doctors often confuse them with “growing pains”. Additionally, gastrointestinal symptoms, decreased sweating and heat intolerance are also common in the early stage of the disease[3].

Effective treatment methods have been developed for Fabry disease, so early diagnosis of the disease is of great practical importance. Unfortunately, some cases are diagnosed at late stages of the disease, which makes it impossible to obtain significant results from enzyme replacement therapy. However, at any stage of the disease, the beginning of treatment allows to slow down the progression and prevent late clinical symptoms, which include renal failure, hypertrophic cardiomyopathy, cerebrovascular and other diseases[4].

Heart disease is the leading cause of death in patients with FD (34% in men and 57% in women)[5]. In this regard, a cardiology screening project is in effect in Russia. It is being implemented by the Medical and Genetic Research Center named after acad. N. P. Bochkov in cooperation with the Petrovax company, is aimed at earlier detection of Fabry disease in patients with cardiac pathologies and is available in all regions of Russia.


1Laney D.A. J. Genet. Couns. 2008

2Laney DA, et al. Genet Med. 2015 May; 17(5):323-30. A Mehta, L Ginsberg, FOS Investigators. tr Suppl. 2005 Mar;94(447):24-7

3Hopkin RJ, Bissler J, Banikazemi M, Clarke L, Eng CM, Germain DP, Lemay R, Tylki-Szymanska A, Wilcox WR. Pediatr Res. 2008 Nov; 64(5):550-5

4Eng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 2006;8:539-48.

5Kampmann C, Wiethoff CM, Whybra C, Baehner FA, Mengel E, Beck M. Acta Paediatr. 2008 Apr; 97(4):463-9.
Previous news

Russia expands the range of drugs for the treatment of cystitis