SNP Shot: Genomic Insights

Transthyretin amyloidosis (ATTR amyloidosis) is a slowly progressing disease where abnormal deposits of a protein called amyloid accumulate in the body's organs and tissues. These amyloid deposits most commonly affect the peripheral nervous system, the network of nerves connecting the brain and spinal cord to muscles and sensory cells responsible for detecting sensations like touch, pain, temperature, and sound. These deposits in the peripheral nerves can lead to peripheral neuropathy, a loss of sensation in the extremities. The autonomic nervous system, which controls involuntary bodily functions like blood pressure, heart rate, and digestion, can also be affected by ATTR amyloidosis. In some instances, the brain and spinal cord (central nervous system) are involved. Other organs that can be affected include the heart, kidneys, eyes, and gastrointestinal tract. The age when symptoms begin to appear varies considerably, typically between 20 and 70 years old.

ATTR amyloidosis has three main forms, differentiated by their specific symptoms and the body systems they primarily affect.

The neuropathic form of ATTR amyloidosis mainly impacts the peripheral and autonomic nervous systems, leading to peripheral neuropathy and problems with controlling automatic bodily functions. These difficulties can include sexual impotence, diarrhea, constipation, urination problems, and a sudden drop in blood pressure upon standing (orthostatic hypotension). Some individuals may also experience heart and kidney complications. Various eye issues can occur, such as clouding of the vitreous humor (vitreous opacity), dry eyes, elevated eye pressure (glaucoma), or pupils with an irregular, "scalloped" shape. Some people with this form develop carpal tunnel syndrome, characterized by numbness, tingling, and weakness in the hands and fingers.

The leptomeningeal form of ATTR amyloidosis primarily affects the central nervous system. In individuals with this form, amyloid deposits occur in the leptomeninges, the two thin tissue layers covering the brain and spinal cord. Protein buildup in this tissue can cause stroke, brain bleeding, fluid accumulation in the brain (hydrocephalus), difficulty with coordination (ataxia), muscle stiffness and weakness (spastic paralysis), seizures, and cognitive decline (dementia). Eye problems similar to those seen in the neuropathic form can also be present. When individuals with leptomeningeal ATTR amyloidosis also experience these associated eye problems, it is referred to as the oculoleptomeningeal form.

The cardiac form of ATTR amyloidosis affects the heart. Individuals with cardiac ATTR amyloidosis may experience an irregular heartbeat (arrhythmia), an enlarged heart (cardiomegaly), or orthostatic hypertension. These heart abnormalities can progress to heart failure and death. Occasionally, individuals with the cardiac form may also experience mild peripheral neuropathy.

Inheritance:

This condition follows an autosomal dominant inheritance pattern, meaning that only one copy of the mutated gene in each cell is enough to cause the disorder. In the majority of cases, an affected individual inherits the mutation from one affected parent. Rarely, cases arise from new mutations in the gene and occur in individuals with no family history of the disorder. However, not everyone who carries a TTR gene mutation will ultimately develop ATTR amyloidosis.