Xiaoqiang, 14 years old, has been suffering from pain since he was 8 years old. At the beginning, her feet hurt, and Xiaoqiang's mother thought that there was a small problem and gave the child some medicine to relieve pain. Xiaoqiang's mother and sister also have symptoms of pain. Later, Xiaolong's finger joints also began to ache, affecting his life, and although he visited the doctor many times, the cause of the pain was not found.
Last summer, Xiaoqiang's mother took him to the Provincial Children's Hospital for treatment, and the doctor carefully asked Xiaoqiang's medical history and learned that in addition to pain, Xiaoqiang had many years of rash, no sweating, bloating, and poor appetite. The doctor combined Xiaoqiang's medical history, pain, no sweating, family history, suspected genetic disease, recommended him to do genetic testing, genetic test results showed GLA gene mutation, he suffered from the rare disease Fabry disease.
Past and present lives
Fabry disease was first reported in 1898 by British physician William Anderson and German Johannes Fabry, hence the name Anderson-Fabry disease or Fabry disease.
Keywords: gene mutation
Fabry disease is a rare X-linked genetic disease, due to the gene mutation of the middle segment of the long arm of the X chromosome encoding α-galactosidase A (α-Gal A), resulting in its structural and functional abnormalities, so that its metabolic substrate trihexanose ceramide (GL-3) and related glycosphingolipids accumulate in a large number of blood vessels, nerves, kidneys, hearts and other tissues and organs in multiple organs of the body, causing structural and functional disorders of corresponding tissues and organs, resulting in clinical syndrome.
Keywords: easy to miss and misdiagnose
Fabry disease can be divided into classic and late-onset, with varying clinical manifestations. Due to the diverse clinical manifestations of Fabry disease and non-specificity, it is easy to miss and misdiagnose clinically. Research data show that patients with Fabry disease have a long time from symptom onset to diagnosis, with an average interval of 14.8 years, and some even decades.
Clinical manifestations of Fabry disease
Keywords: genetic testing and biopsy of diseased tissue
Since Fabry disease is associated with GLA gene mutations, genetic testing is an important means of diagnosis. However, the pathogenicity of GLA gene variants detected in some patients is unclear, and biopsy of diseased tissues such as skin, myocardium, kidney, or nerve tissue is required to aid diagnosis. At the same time, the diagnosis was combined with the patient's family history, clinical manifestations of multi-system involvement, α-Gal A enzyme activity, biomarker (Lyso-GL-3) and other indicators.
The specific reference values are:
1. Galactosidase A activity ≤ normal value of 3% in classic male patients; Galactosidase A activity ≤ normal value in nonclassical male patients;
2. Plasma lyso-Gb3≥ 2.7 ng/ml in organ affected; Plasma lyso-GB3 in patients without organ involvement
3. Nonclassical type needs to be diagnosed by tissue biopsy (pathological manifestations of cell vacuolar degeneration, electron microscopy ultrastructure visible medullary body deposition).
Keywords: symptomatic treatment and disease-specific treatment
Since Fabry disease involves multiple tissues and organs, symptomatic treatment is mainly for the involvement of each organ to give corresponding treatment, such as pain relief. Pain symptoms are relieved with carbamazepine and proteinuria is reduced with ACE/ARB; dialysis or kidney transplantation for patients with kidney failure, etc.
Enzyme replacement therapy (ERT) is used to prevent or delay the onset of multisystem lesions. SUCH AS FABRAZYME, REPLAGAL AND SO ON. In addition, chaperones, stem cells and gene-targeted therapies are being studied.
Bibliography:
1. China Fabry Disease Expert Collaboration Group. Expert consensus on the diagnosis and treatment of Fabry disease in China (2021 edition)[J].Chinese Journal of Internal Medicine, 2021, 60(4): 321-330.)
2、Zampetti A, et al: Angiokeratoma: decision-making aid for the diagnosis of Fabry disease. Br J Dermatol 2012, 166(4):712-720.
3、Germain DP: Fabry disease. Orphanet J Rare Dis 2010, 5:30.
4、Nowicki M, et al: Enzyme replacement therapy in Fabry disease in Poland: a position statement. Pol Arch Intern Med 2020, 130(1):91-97.
5、Wanner C, et al: European expert consensus statement on therapeutic goals in Fabry disease. Mol Genet Metab 2018, 124(3):189-203.
Source | Metz Medicine
Edit | Lan Ying