Familial Amyloidosis, Finnish Type (FAF), also called hereditary gelsolin amyloidosis and AGel amyloidosis (AGel), is an amyloid condition with a number of associated cutaneous and neurological presentations deriving from the aberrant

proteolysis Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...

of a mutated form of

plasma gelsolin Plasma gelsolin (pGSN) is an 83 kDa abundant protein constituent of normal plasma and an important component of the innate immune system. The identification of pGSN in ''Drosophila melanogaster'' and ''C. elegans'' points to an ancient origin ea ...

. First described in 1969 by the Finnish ophthalmologist Jouko Meretoja, FAF is uncommon with 400–600 cases described in Finland and 15 elsewhere.

Clinical presentation

The disorder is primarily associated with eye, skin, and cranial nerve symptoms with the onset of symptoms appearing between the thirties and fifties. The most common characteristic is type II lattice corneal dystrophy with other signs such as

polyneuropathy Polyneuropathy ( poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hand ...

dermatochalasis Dermatochalasis is a medical condition, defined as an excess of skin in the upper or lower eyelid, also known as "baggy eyes." It may be either an acquired or a congenital condition. It is generally treated with blepharoplasty. Presentation Ass ...

, open-angle glaucoma, bilateral progressive

facial paralysis Facial nerve paralysis is a common problem that involves the paralysis of any structures innervated by the facial nerve. The pathway of the facial nerve is long and relatively convoluted, so there are a number of causes that may result in facial ...

, cutis laxa, skin fragility with ecchymosis, facial mask, diffuse hair loss, dry skin, carpal tunnel syndrome,

nephrotic syndrome Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy ...

cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...

with conduction alterations, and early aging associated with the condition. There are no specific treatments available.

Plasma gelsolin amyloid

Plasma gelsolin Plasma gelsolin (pGSN) is an 83 kDa abundant protein constituent of normal plasma and an important component of the innate immune system. The identification of pGSN in ''Drosophila melanogaster'' and ''C. elegans'' points to an ancient origin ea ...

is a 755 amino acid, 83 kDa plasma protein involved in the regulation and resolution of inflammation. It is made up of six "gelsolin domains," each consisting of a 5–6 strand β-sheet between one long and one short α-helix. Several single point mutations in the GSN gene will lead to loss of structure in residues 254–258 of the second domain. The misfold and associated increased flexibility opens up a cleavage site to the enzyme furin. Plasma gelsolin is cleaved as it passes through the Golgi before being secreted from the cell. A 68 kDa C-terminal fragment is further endoproteolysed into 5 and 8 kDa fragments that are amyloidogenic. The most common mutations are D187N/Y (G654A/T on gene GSN, chromosome 9) with additional reports of G167R, N184K, P432R, A551P, and Ala7fs in the medical literature. Mutations are inherited in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

fashion.

Names

Many names exist in the scientific literature in reference to this disease including: * Familial amyloid neuropathy type IV * Familial amyloidotic polyneuropathy (FAP) type IV * Lattice corneal dystrophy, gelsolin type * Lattice corneal dystrophy type 2 (LCD2) * Meretoja’s syndrome

References

External links

{{Medical resources , ICD10 = E85.1 , ICD9 = , ICDO = , OMIM = 105120 , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 85448 Amyloidosis Skin conditions resulting from errors in metabolism

Clinical presentation

Plasma gelsolin amyloid

Names

See also

References

External links