To help recognize Fabry disease, there are landmark signs and symptoms you should be aware of that can help to pull the pieces together to help lead to the diagnoses.

There is a classic type of pain associated with Fabry disease that can be described as a chronic burning or tingling pain in the hands and feet, or as an itching or crawling sensation under your skin. This is typically the first symptom that brings the patient to the doctor's office and is called acroparesthesia. This pain usually begins in childhood and can occur daily.

Another form of Pain associated with Fabry disease is known as a “Fabry Crisis” This type of pain, can be described as a stabbing or agonizing, incapacitating pain which radiates inwards from hands and feet. It can last as briefly as a few minutes or as long as a week. This pain can be triggered by fever, exercise, stress and weather changes. The exact cause of this pain is unknown. One of the possible causes is thought to be GL-3 deposits in endothelial cells of microvasculature surrounding the peripheral nervous system.

Skin Finding: Angiokeratomas are recognizable dermatological symptoms. These are reddish-purplish skin lesions that can vary from pinpoint to several mm in size. They are typically distributed in regions where the skin folds or where stretching occurs: between umbilicus and knees, penis, breasts, trunk, back, in oral mucosa and underside of tongue. These lesions are non-painful; they do not itch nor will they blanch when compressed. These angiokeratomas are found in 70% of males by age 17 and become more numerous with age.

Other dermatologic symptoms include hypohidrosis or anhidrosis, this is either a decreased or inability to sweat. It is important for Fabry patients to drink plenty of water and pace themselves to avoid overheating. 50% of men have reduced tear and saliva production which makes them prone to heat and cold intolerance. It has been noted that this can also lead to episodic pain and nausea. Children often have frequent fevers without sweating. Fabry patients, especially adolescents often have reduced energy levels. This fatigue may limit the amount of activity in which they can participate.

Eye Finding: Ocular symptoms include corneal opacities which are described as either whorled or spoke-like patterns on the cornea or feathery features when examined with a slit lamp. Examinations with a slit lamp is not usually apart of a routine eye exam. Greater than 90% of males will have some type of opacity and 80-90% of females will have these corneal whorls. These corneal opacities do not affect vision.

Other Ocular manifestations include conjunctival and retinal lesions. Neither of these lesions affect vision and are thought to be caused by vascular endothelial GL-3 accumulation in the ocular vessels. Retinal changes are often associated with advanced disease. (Note the tortuosity of the vessels)

Hearing and Auditory Finding: Auditory involvement includes tinnitus (Ringing in Ears) and hearing loss. These conditions affect greater than 60% of males, and 20% of females

Gastrointestinal Finding: Symptoms include a wide spectrum of gastrointestinal involvement and are believed to be under reported. Symptoms vary but may include episodic diarrhea, abdominal pain, nausea and vomiting, bloating after meals and acute intermittent abdominal cramping. It is estimated that 70% of males and 30% of females experience these gastrointestinal symptoms.

Renal failure is the most common cause of medical complications.

Left Ventricular Hypertrophy (Markedly thicken myocardium)

Heart Involvement includes ventricular enlargement, cardiomyopathy and valvular insufficiency. The most common finding is concentric left ventricular hypertrophy of unknown causes. (As noted below) Other symptoms include conduction abnormalities and arrhythmias and coronary artery disease. Heart failure is the second most common cause of morbidity.

Cerebrovascular complications can include multifocal small vessel ischemic strokes, hemiplegia and TIA’s. These events involve thrombosis of smaller vessels. With Fabry disease, the posterior (basilar artery) circulation is the primary site for GL-3 accumulation.

	MRI Scans are used to evaluate brain involvement

It is estimated that > 50% of patients over 35 years old have experienced small white matter infarcts. The clinical significance of these infarcts is unknown at this time. Strokes may in fact be the most concerning manifestation associated with Fabry disease involving the major organs.