Other Types of Amyloidosis

AA amyloidosis occurs in a small number of patients who have experienced a long-standing inflammatory or infectious disease in which excessive amounts of a protein called Serum Amyloid A (SAA) are produced as a biproduct of the normal immune response. For reasons that are unknown, SAA proteins at some point become misfolded and deposit as amyloid. While these misfolded proteins mostly affect the kidneys, they can sometimes affect the liver and spleen as well. Treatment for AA amyloidosis is geared towards controlling the problems associated with the underlying inflammatory or infectious disease. Improvements in treatments for inflammatory diseases and chronic infections have led to a decline in AA amyloidosis in recent years, especially in developed countries.

ALECT2 amyloidosis is a recently recognized form of amyloidosis involving a protein called leukocyte chemotactic factor 2 (LECT2) which normally circulates in the blood and helps repair damaged tissue by attracting white blood cells. The underlying reason which causes LECT2 proteins to become abnormal and misfold is currently unknown. Excessive amounts of the LECT2 protein are not produced in patients and there have not been any mutations in the LECT2 gene identified thus far. ALECT2 amyloidosis appears to be more common in the elderly population of certain ethnic groups including those of Mexican, Native American, Punjabi, North African and Middle Eastern descent. This type of amyloid deposits have been most commonly found in the kidneys; however, they may also be found in the liver, adrenal glands and spleen. Experts believe that ALECT2 amyloidosis is underdiagnosed and may be a more common cause of kidney failure than currently suspected. While there are currently no existing treatments for this type of amyloidosis, research continues to grow in this area.

Aß2M amyloidosis is a type of amyloidosis that is normally associated with patients who have been on kidney dialysis for more than five years. It is caused by the progressive build-up of the beta 2 microglobulin (Aß2M) protein, which is not effectively cleared by dialysis. Over time, the Aß2M proteins become abnormal, misfold and deposit as amyloid, primarily around the bones and joints. As modern dialysis procedures have improved, Aß2M amyloidosis is becoming much less common.

Apolipoprotein amyloidosis is caused by one of several proteins belonging to a family of proteins called apolipoproteins, which normally play important roles in the transport and metabolism of cholesterol and fat in the body. There are currently five types of apolipoprotein amyloidosis known to form, most of which are hereditary – caused by a fault or mutation in the respective apolipoprotein gene, which is transmitted from parents to their offspring.  This genetic mutation results in an abnormal apolipoprotein that is unstable and  misfolds to form amyloid deposits in various tissues and organs, depending on the type of apolipoprotein. The types of apolipoprotein which are known to form amyloid include: Apolipoprotein amyloidosis is caused by one of several proteins belonging to a family of proteins called apolipoproteins, which normally play important roles in the transport and metabolism of cholesterol and fat in the body. There are currently five types of apolipoprotein amyloidosis known to form, most of which are hereditary – caused by a fault or mutation in the respective apolipoprotein gene, which is transmitted from parents to their offspring.  This genetic mutation results in an abnormal apolipoprotein that is unstable and  misfolds to form amyloid deposits in various tissues and organs, depending on the type of apolipoprotein. The types of apolipoprotein which are known to form amyloid include:

• Apolipoprotein A-I (AApoA-I) – affects the heart, liver and peripheral nervous system
• Apolipoprotein A-II (AApoA-II) – primarily affects the kidneys
• Apolipoprotein A-IV (AApoA-IV) – affects the kidneys and heart
• Apolipoprotein C-II (AApoC-II) – primarily affects the kidneys
• Apolipoprotein C-III (AApoC-III) – primarily affects the kidneys

Hereditary fibrinogen (AFib) amyloidosis is caused by a fault or mutation in the hereditary fibrinogen alpha chain gene, passed down from parents to their offspring. Fibrinogen forms in the liver and plays a central role in blood clotting. Mutations in the fibrinogen gene give rise to an abnormal fibrinogen protein, which then misfolds and aggregates to form amyloid deposits. To date, 16 mutations in the fibrinogen alpha chain gene have been identified, which cause hereditary fibrinogen amyloidosis. All mutations cause amyloidosis and primarily affect the kidneys. While there are currently no existing treatments for this type of amyloidosis, research continues to grow in this area.

Hereditary gelsolin (AGel) amyloidosis is caused by a fault or mutation in the hereditary gelsolin gene, passed down from parents to their offspring. Gelsolin is found in the cytoskeleton and helps provide shape and structure for cells. Mutations in the gelsolin gene produce abnormal gelsolin proteins that are unstable and misfold to form amyloid deposits in the cranial nerves (emerging from the brain), eyes, skin and kidneys. This type of amyloidosis originated in Finland and has since been reported in other countries. Thus far, four different mutations in the gelsolin gene have been identified, which cause amyloidosis. While there are currently no existing treatments for this type of amyloidosis, research continues to grow in this area.

Hereditary lysozyme (ALys) amyloidosis is caused by a fault or mutation in the hereditary lysozyme gene, passed down from parents to their offspring. Lysozyme, an enzyme found in tears and mucus, plays an important role in reducing infections by breaking down bacterial cell walls. Mutations in the lysozyme gene produce abnormal lysozyme proteins, which misfold and aggregate to form amyloid deposits. There are currently a total of nine different mutations known to cause ALys amyloidosis; depending on the mutant gene, a variety of organs are affected, including the kidneys, digestive system and exocrine glands (tear, salivary and sweat glands). While there are currently no existing treatments for this type of amyloidosis, research continues to grow in this area.