Visceral familial amyloidosis (Amilioidosis type VIII, amyloidosis type Ostertag, amyloidosis familial renal, nonneuropathic systemic amyloidosis) (visceral Familial amyloidosis, Ostertag-type amyloidosis, Familial renal amyloidosis, Systemic non-neuropathic amyloidosis) - Genes LYZ, APOA1, FGA and B2M

Amyloidosis are sporadic a group of processes, family and / or hereditary degenerative, linked to deposit in tissues affected abnormal folded protein (amyloid). When deposited on fabrics, amyloid disrupts normal tissue structure, and thus tissue function. Signs and symptoms of each process depend on the location and size of deposits. Deposits can be located (localized amyloidosis) or distributed throughout the body (systemic amyloidosis). They can also be differentiated according to their etiology, secondary (caused by another disease), or primary (cause unknown). Primary amyloidosis generally affect nerves, skin, tongue, joint, heart and liver. Secondary amyloidosis usually affect spleen, kidney, liver and adrenal glands.

Visceral familial amyloidosis is due to a mutation in one or more of the following genes: gene lysozyme (LYZ), apolipoprotein A1 (APOA1) gene, the alpha chain of fibrinogen (FGA), or gene encoding the ?-2 microglobulin (B2M). The latter, mainly in secondary long - term hemodialysis cases.

The LYZ gene, located on the long arm of chromosome 12 (12q15), encoding human lysozyme, which is the natural substrate peptidoglycan of bacterial cell walls cleaving the glycosidic linkages existing ?-(1-4) linkages between N- acetylmuramic and N-acetylglucosamine. We found missense mutations in cases of this type of amyloidosis. Mutations in the gene LYZ are responsible for a type of amyloidosis which affects internal organs, but not affect the nervous system. In other cases, there are deposits of Apolipoprotein A1, fibrinogen and lysozyme amyloid. Clinically they are characterized by renal involvement with nephrotic syndrome, hypertension, hepatosplenomegaly, petechial rash and cholestasis.

The APOA1 gene, located on the long arm of chromosome 11 (11q23-q24), encoding apolipoprotein A-1 (apoA-I), the main component of high density lipoproteins (HDL) plasma. This protein also promotes efflux of cholesterol from tissues to the liver for excretion, and is a cofactor for the "lecithin-cholesterol transferase (LCAT: Lecithin cholesterol acyltranferase), responsible of most cholesterol esters in plasma. Alterations in this gene have been associated with deficiencies of type 2 HDL, including Tangier disease, and systemic amyloidosis nonneuropathic. A mutation of this gene has also been found in the Iowa amyloidosis polineuropática nephropathic type (type III). Mutations in the gene result APOA1 amyloidosis usually affects the liver, kidneys and heart. Depending on the organs involved, the signs and symptoms of the disease can vary. In addition, affected individuals may have hepatomegaly, chronic kidney disease or heart disease such as cardiomyopathy. However, in some people, the disease is very mild and causes no apparent symptoms or signs.

The FGA gene (Fibrinogen alpha chain), located on the long arm of chromosome 4 (4q28), encoding the protein "Fibrinogen alpha chain A (Aa)", a part of the protein fibrinogen. This protein is important for coagulation. To form the fibrinogen Aa chain the, two other proteins called fibrinogen B beta chains (B.beta) and fibrinogen gamma (?), each encoded by a different gene bind. Mutations of these genes occur afibrinogenemias, processes accompanied by bleeding absence of blood protein fibrinogen. Most mutations cause a shortening of the protein, and if something should occur fibrinogen Aa would not be functional. Mutations in one or both copies of the FGA gene, can cause other bleeding disorders as hypofibrinogenemia, Dysfibrinogenemia, or hypodysfibrinogenemia. Alterations in this gene have been found in some cases of hereditary renal amyloidosis, resulting in the deterioration of kidney function and leading to kidney failure. Renal familial amyloidosis is characterized by the accumulation of amyloid deposits in the kidneys. When the disease is caused by genetic mutations FGA, amyloid deposits are composed of proteins abnormal fibrinogen Aa, so sometimes it is called amyloidosis Fibrinogen. Mutations involved often change a single amino acid in the chain of fibrinogen Aa and do not appear to affect the activity of fibrinogen clotting.

The B2M gene, located on the long arm of chromosome 15 (15q21-q22.2), encoding ?-2 microglobulin. This protein, when adopting the fibril configuration causes some disease states. Fibril formation is concentration dependent. In patients with persistent high levels of ?-2-microglobulin, it may involve a box systemic amyloidosis, as has been observed in cases of long term hemodialysis.

This disease usually inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. In most cases, an affected person has a parent with the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with familial amyloidosis visceral, by complete PCR amplification of the exons of LYZ, APOA1, FGA and B2M, respectively, genes and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).