Hereditary amyloidosis

A familial (inherited) disorder in which protein deposits (amyloid) accumulate in one or more organ systems in the body. Hereditary amyloidosis is a relatively uncommon cause of amyloidosis. The more common forms of amyloidosis are primary an secondary amyloidosis. However, hereditary amyloidosis is found worldwide. It occurs in families of nearly every ethnic background. The protein deposits in hereditary amyloidosis are made up of the transthyretin or TTR protein. The transthyretin protein is manufactured in the liver, and it is a mutation of this protein that causes hereditary amyloidosis. More than 50 different mutations in transthyretin are known in connection with this type of amyloidosis. There are also other proteins which, when mutated, can cause familial amyloidosis, but these situations are quite rare. (These proteins include apolipoprotein A1, gelsolin, fibrinogen, and lysozyme.) In hereditary amyloidosis, the nervous system and gastrointestinal tract are often involved. This can cause numbness and tingling in the arms and legs, dizziness upon standing, and diarrhea. Each family with hereditary amyloidosis has its own pattern of organ involvement and associated symptoms. The mode of transmission in hereditary amyloidosis is autosomal dominant, which means that if a male or female has this type of amyloidosis each of their children has a 1-in-2 (50%) chance of inheriting the same mutation and of having the same disease. If the child does not inherit the gene, he/she cannot pass it on to future generations. The only treatment that offers a potential cure for hereditary amyloidosis is liver transplantation. Since the transthyretin protein which causes familial amyloidosis is made in the liver, replacing this organ removes the source of mutant protein production. A new liver should make entirely normal transthyretin. Whether or not previously formed amyloid TTR deposits will disappear after liver transplantation is uncertain and is under study.

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any inherited form of amyloidosis. The term is usually used to denote various systemic autosomal dominant disorders of amyloid deposition involving the nervous system (polyneuropathies). The most common form isATTR amyloidosis, which is associated with various point mutations of the TTR gene; rare mutations of other proteins can also be a cause. The term is less commonly used to describe AA amyloidosis in which the fibril deposition is associated with an inherited disease (e.g., familial Mediterranean fever). Subclassifications are based on clinical presentation and the biochemical composition of the fibrils deposited; originally the subclasses were distinguished on the basis of kinship. Called also familial or heredofamilial a.; see also familial amyloid polyneuropathy, under polyneuropathy.