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Media Gallery

Familial renal amyloidosis. Proposed mechanism for amyloid fibril formation. The drawing depicts a generic amyloid fibril precursor protein (1) in equilibrium with a partially unfolded, molten, globulelike form of the protein (2) and its completely denatured state (3). Autoaggregation through the beta domains initiates fibril formation (4), providing a template for ongoing deposition of precursor proteins and for the development of the stable, mainly beta-sheet, core structure of the fibril (5). The amyloidogenic precursor proteins in patients with familial renal amyloidosis are thought to be less stable than their wild-type counterparts, causing them to populate intermediate, molten, globulelike states more readily.
Familial renal amyloidosis. An extended kindred with hereditary amyloidosis associated with fibrinogen A alpha-chain Glu526Val; disease penetrance is high in this particular family.
Familial renal amyloidosis. Partial DNA sequence of the gene associated with fibrinogen A alpha-chain Glu526Val in a patient with familial renal amyloidosis, and a sequence from a healthy control. The mutation, which alters codon 526 from glutamic acid to valine, is marked with an arrow.
Familial renal amyloidosis. Progression of amyloid deposits in a patient with amyloidosis associated with fibrinogen A alpha-chain Glu526Val. These serial posterior, whole-body, scintigraphic images were obtained following intravenous injection of iodine-123 (123I)–labeled human serum amyloid P component into a 48-year-old man with hereditary amyloidosis associated with fibrinogen A alpha-chain Glu526Val in whom asymptomatic proteinuria had been identified. Both parents were alive and well and older than age 80 years. The scan at diagnosis (left) showed modest abnormal uptake into renal amyloid deposits, which increased at follow-up 3 years later (right). The remainder of the image represents a normal distribution of tracer throughout the blood pool.
Familial renal amyloidosis. Regression of amyloidosis associated with fibrinogen A alpha-chain Glu526Val following hepatorenal transplantation. The pictures are serial anterior, whole-body, scintigraphic images obtained following intravenous injection of iodine-123 (123I)–labeled human serum amyloid P component into a patient with amyloidosis associated with fibrinogen A alpha-chain Glu526Val. Prior to hepatorenal transplantation (left), heavy amyloid deposition was present in an enlarged liver and spleen. No amyloid deposits were identified in a follow-up study obtained 42 months after hepatorenal transplantation (right); only a normal distribution of tracer is present throughout the blood pool.
Familial renal amyloidosis. Regression of amyloidosis associated with apolipoprotein AI Gly26Arg following hepatorenal transplantation. These serial anterior, whole-body, scintigraphic images were obtained following intravenous injection of iodine-123 (123I)–labeled human serum amyloid P component into a patient with hereditary amyloidosis associated with apolipoprotein AI Gly26Arg. Prior to hepatorenal transplantation (left), heavy amyloid deposition was present in the liver, obscuring the kidneys. Two years after combined hepatorenal transplantation (right), a follow-up scan was normal, showing tracer distributed evenly throughout the background blood pool, including the transplanted organs. Splenic amyloid deposits that were evident initially in posterior scans had regressed at follow-up.

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Table. Recognized Genotypes and Their Associated Phenotypes in Familial Renal Amyloidosis

Table. Recognized Genotypes and Their Associated Phenotypes in Familial Renal Amyloidosis

Amyloid Fibril Precursor Protein	Organs/Tissues Predominantly Affected by Amyloid and Common Clinical Features	Ethnic Origin of Affected Kindreds
Lysozyme Ile56Thr	Renal - Proteinuria and renal failure Skin - Petechial rashes Liver and spleen - Organomegaly (usually well-preserved function)	2 British families (possibly related)
Lysozyme Asp67His	Renal - Proteinuria and renal failure GI tract - Bleeding and perforation Liver and spleen - Organomegaly and hepatic hemorrhage Salivary glands – Sicca syndrome	Single British family
Lysozyme Try64Arg	Renal - Proteinuria and renal failure GI tract - Bleeding and perforation Salivary glands – Sicca syndrome	Single French family
Lysozyme Trp82Arg	Renal - Proteinuria and renal failure	Single Chinese family
Apolipoprotein AI wild type	Amyloid deposits in human aortic atherosclerotic plaques	20-30% of elderly individuals at autopsy
Apolipoprotein AI Gly26Arg	Renal - Proteinuria and renal failure Gastric mucosa - Peptic ulcers Peripheral nerves - Progressive neuropathy Liver and spleen - Organomegaly (usually well-preserved function)	Multiple families (mostly of northern European extraction)
Apolipoprotein AI Trp50Arg	Renal - Proteinuria and renal failure Liver and spleen - Organomegaly and liver failure	Single Ashkenazi family
Apolipoprotein AI Leu60Arg	Renal - Proteinuria and renal failure Liver and spleen - Organomegaly (usually well-preserved function) Cardiac (rarely) - Heart failure	British and Irish kindreds
Apolipoprotein AI deletion 60-71 insertion 60-61	Liver - Liver failure	Single Spanish family
Apolipoprotein AI Leu64Pro	Renal - Proteinuria and renal failure Liver and spleen - Organomegaly	Single Canadian-Italian family
Apolipoprotein AI deletion 70-72	Renal - Proteinuria and renal failure Liver and spleen - Organomegaly (usually well-preserved function) Retina - Central scotoma	Single family of British origin
Apolipoprotein AI Leu75Pro	Renal - Proteinuria and renal failure Liver and spleen - Organomegaly	Italy – Variable penetrance
Apolipoprotein AI Leu90Pro	Cardiac - Heart failure Larynx - Dysphonia Skin – Infiltrated yellowish plaques	Single French family
Apolipoprotein AI deletion Lys107	Aortic intima - Aggressive early-onset ischemic heart disease	Single Swedish patient at autopsy
Apolipoprotein AI Arg173Pro	Cardiac - Heart failure Larynx - Dysphonia Skin - Acanthosis nigricans-like plaques	British and American families
Apolipoprotein AI Leu174Ser	Cardiac - Heart failure	Single Italian family
Apolipoprotein AI Ala175Pro	Larynx - Dysphonia Testicular - Infertility	Single British family
Apolipoprotein AILeu178His	Cardiac - Heart failure Larynx – Dysphonia Skin - Infiltrated plaques Peripheral nerves – Neuropathy	Single French family
Apolipoprotein AII Stop78Gly	Renal - Proteinuria and renal failure	American family
Apolipoprotein AIIStop78Ser	Renal - Proteinuria and renal failure	American family
Apolipoprotein AIIStop78Arg	Renal - Proteinuria and renal failure	Russian family, Spanish family(different nucleotide substitutions in the two kindreds)
Fibrinogen A alpha-chain Arg554Leu	Renal - Proteinuria and renal failure	Peruvian, African American and French families
Fibrinogen A alpha-chain frame shift at codon 522	Renal - Proteinuria and renal failure	Single French family
Fibrinogen A alpha-chain frame shift at codon 524	Renal - Proteinuria and renal failure	Single American family
Fibrinogen A alpha-chain Glu526Val	Renal - Proteinuria and renal failure Late-onset liver (rarely) - Organomegaly and liver failure	Multiple families (northern European extraction, variable penetrance)
Fibrinogen A alpha-chain Gly540Val	Renal - Proteinuria and renal failure	Single German family
Fibrinogen A alpha-chain Indel 517-522	Renal - Proteinuria and renal failure	Single Korean child

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