Fabry disease is a rare X-linked recessive disorder with an incidence of 1 in 40,000 to 1 in 60,000 males. This view has been challenged by the fact that female patients have relatively mild symptoms and appear later. The mechanism of pathogenesis is the lack of αCGal A. The αC galactosidase A (αCGal A) in the human cytosol hydrolyzes the α-galactose residue at the end of the neurospherin lipids (mostly the triple hexose ceramide globotriaosylceramide (GL3)). The normal degradation of GL3 is hindered due to the absence of the causative gene GLA, and the undegraded substrate accumulates in the cellular lysosomes of various tissues such as heart, liver, kidney, eye, brain and nerves and blood vessels of the skin, causing ischemia and infarction of tissues and organs. The clinical manifestations of Fabray disease are complex Patients with Fabray disease may present with a single symptom in the early stages and gradually show signs of multi-organ damage as they age. The main clinical manifestations of classic Fabray disease are: (1) Abnormal sensation in the extremities: intermittent episodes of severe burning or tingling pain in the extremities (hands and feet) starting in childhood and early adolescence, lasting from a few minutes to several days, without significant local redness or swelling. Laboratory tests lacked positive characteristic changes, and CRP and all immune indexes were normal; no abnormal changes were seen on hand and foot X-ray skeletal examination. The pain can be triggered or aggravated by exercise, fatigue, mental stress or rapid changes in temperature and humidity. (2) Cutaneous angiokeratoma and oligohidrosis: Patients with Fabray disease often have little or no sweating since childhood, are heat intolerant, and have occasional hypothermia. With age, cutaneous angiokeratomas appear from the umbilicus to the knee (the so-called “sitting area”), mostly in the umbilicus, scrotum, groin and buttocks bilaterally symmetrical distribution of small dots of red-black capillary dilation, accompanied by epidermal cell proliferation, which do not fade when pressed, and can only be detected by careful examination. (3) Ocular symptoms: turbid clouding of the cornea extending from the center to the periphery. 30% of men can observe fine granular material in the posterior capsule of the lens under slit lamp, called “Fabry cataract”. Retinal and conjunctival aneurysms and vascular distortions are seen. (4) Renal lesions: Protein, tubular and red blood cells can be detected in the urine in childhood and adolescence, with increasing proteinuria and progressive deterioration of renal tubular function with age. (5) Vascular lesions: Most patients with Fabray disease will develop symptoms of cardiac lesions in middle age, and severe cases may lead to congestive heart failure, sudden death or myocardial infarction. In addition, 69% of patients with Fabray disease have gastrointestinal symptoms, cerebrovascular lesions, respiratory symptoms, and psychological problems such as high-frequency hearing loss, impotence, weakness, and anxiety and depression. In addition to the classic form, there are renal variant and cardiac variant. The renal variant is often misdiagnosed as end-stage renal disease of unknown origin, and most do not present with angiokeratomas, abnormal sensation in the extremities, oligohidrosis or corneal clouding, and may have moderate to severe left ventricular hypertrophy. Male patients with cardiac variant also lack the typical clinical manifestations of Fabray’s disease. Instead, the manifestations of hypertrophic cardiomyopathy with left ventricular hypertrophy, left heart insufficiency and mitral valve insufficiency as the main manifestations appear only at the age of 60-80 years, and may be accompanied by moderate proteinuria but normal renal function. So far, 35 cases of Fabray disease have been diagnosed in the genetic counseling clinic of Peking Union Medical College Hospital, all of them are classic, which is considered to be related to the fact that most of the patients are children. The phenotype of Fabray disease is highly variable and often presents with multi-organ symptoms, with no specific changes on routine examination. Pain is often diagnosed as growing pains, juvenile rheumatoid arthritis, Raynaud’s syndrome, neuritis, erythromelalgia, or even neurosis or psychiatric abnormalities; gastrointestinal symptoms are thought to be gastroenteritis, dyspepsia, etc.; skin rashes are thought to be bleeding spots; kidney changes such as urine protein are diagnosed as chronic nephritis, nephropathy, etc.; patients with cardiac involvement are diagnosed as arrhythmia, hypertrophic cardiomyopathy, etc. The key to confirming the diagnosis of this disease is to take a detailed medical history, family history and physical examination, to recognize the typical signs of Fabray disease, and to think of the following confirmatory tests for suspected cases. Enzymatic diagnosis: Detection of αC galactosidase activity in peripheral blood leukocytes or skin fibroblasts of patients with Fabray disease is currently the most effective, reliable and simple method recognized internationally. α-Gal A enzyme activity in classic patients is severely deficient, usually below 1% of normal. The enzyme activity is also significantly lower in both variants, but usually >1%. Since some carriers can have alpha-Gal A enzyme activity in the normal range, detection of carriers by enzymatic testing is not reliable. GLA gene mutation test: Also a reliable method for confirming the diagnosis of patients with Fabray disease and the only method for identifying female heterozygotes. In institutions where enzymatic testing is not possible, the pathological diagnosis of Fabray disease can also be made by the presence of typical osmiophilic inclusion bodies in cells observed on biopsy of small blood vessels in the skin, nerve fibers or kidney tissue. Enzyme replacement therapy Enzyme replacement therapy (ERT) is currently the most effective treatment for Fabray disease, reversing its metabolic and pathological abnormalities. Approved for clinical use by the US FDA in 2004, ERT can remove GL3 from plasma and endothelial cells in the heart, kidney, skin and other important organs, and has a positive effect on relieving symptoms, delaying disease progression and improving quality of life, especially emphasizing the importance of early treatment. However, these drugs are very expensive and have not yet entered the Chinese market. Other drugs that have entered the clinical trial stage are “molecular chaperones”. These are small galactose-like compounds that bind to the active site of α-Gal A in vivo and promote the correct folding, processing and dimer formation of enzymatic protein polypeptides, preventing misfolding and degradation of mutated abnormal enzymes by proteases. Currently, they are mainly used in the treatment of patients with cardiac variants that still have some residual enzyme activity. These drugs are oral formulations that are easy to take, have few side effects, and are relatively inexpensive. Other treatments that have not yet entered the clinic are: glycosphingolipid synthase inhibitors, bone marrow transplantation, etc. Gene therapy is still in the experimental stage in animal models. Conclusion Fabray disease is an X-linked recessive disorder with significant familial aggregation and rare de novo mutations. Mothers of male patients are usually carriers of the disease-causing gene. Each pregnancy in female carriers has a 50% chance of transmitting the disease-causing gene to the offspring, which means that a boy will have a 50% chance of being a patient and a girl will have a 50% chance of being a carrier. Sons of male patients are normal and daughters will all be positive carriers. Therefore, when a patient with Fabray disease is found in a family, accurate and effective genetic counseling should be conducted for the rest of the family.