Finnish type amyloidosis

Finnish type amyloidosis, also known as Meretoja syndrome or hereditary gelsolin amyloidosis, is a rare and inherited form of systemic amyloidosis.

Characteristics:

• Unique constellation of features: The disorder is characterized by a unique combination of symptoms, including:
  • Lattice corneal dystrophy (LCD)
  • Cranial neuropathy
  • Bulbar signs (e.g., dry eyes, blurred vision)
  • Skin changes (e.g., thickening, pigmentation)
• Peripheral neuropathy and renal failure: Some patients may develop peripheral neuropathy and renal failure as the disease progresses.

Inheritance pattern:

• Autosomal dominant trait: The disorder is inherited in an autosomal dominant pattern, meaning that every child whose parents are carriers of the mutated gene has a 50% chance of inheriting the condition.

Prevalence:

• Rare and uncommon: Finnish type amyloidosis is one of the most uncommon genetic subtypes of hereditary amyloidosis in clinical practice.
• Common in Finland: The disorder is relatively common in Finland, where it was first described by ophthalmologist Dr. Jouko Meretoja in 1969.

References:

• [3] Finnish type amyloidosis is characterized clinically by a unique constellation of features including lattice corneal dystrophy, and cranial neuropathy, bulbar signs, and skin changes.
• [12] The disorder is usually inherited in an autosomal dominant pattern.
• [14] Meretoja disease or hereditary gelsolin amyloidosis is one of the approximately 30 hereditary diseases particular to Finland.

Finnish type amyloidosis, also known as hereditary gelsolin amyloidosis or Meretoja syndrome, is a rare genetic disorder characterized by the accumulation of abnormal proteins (amyloid) in various tissues. The condition manifests with a range of symptoms and signs, which can be broadly categorized into three main areas: ophthalmological, neurological, and dermatological.

Ophthalmological Signs

• Corneal lattice dystrophy: This is one of the earliest and most distinctive features of Finnish type amyloidosis. It presents as a characteristic lattice-like pattern on the cornea.
• Impaired vision: As the condition progresses, patients may experience impaired vision due to the accumulation of amyloid in the eyes.

Neurological Signs

• Cranial neuropathy: The facial nerve is often affected, leading to symptoms such as facial weakness or paralysis.
• Polyneuropathy: Patients may experience numbness, tingling, or weakness in their extremities.
• Bulbar signs: These can include symptoms such as difficulty swallowing or speaking.

Dermatological Signs

• Cutis laxa: This is a condition characterized by loose, sagging skin.
• Skin fragility: Patients with Finnish type amyloidosis may experience fragile skin that is prone to bruising or tearing.
• Increased skin fragility and fragility of other tissues are also common.

It's worth noting that the symptoms of Finnish type amyloidosis can develop slowly over time, and patients may not always exhibit all of these signs. However, early recognition and diagnosis are crucial for effective management and treatment of this condition.

References:

[3] The most common clinical signs in patients with AGel amyloidosis are progressive ophthalmological (corneal lattice amyloidosis), neurological (cranial neuropathy, bulbar signs, polyneuropathy), and dermatological (cutis laxa) manifestations. [4] [5] In the clinical course of Finnish gelsolin amyloidosis eye problems appear at first, followed later on by impaired vision, polyneuropathy, facial nerve paresis, cutis laxa, skin fragility, and less frequently hearing loss. [6] Gelsolin amyloid fibrils accumulate in tissues, leading to corneal lattice dystrophy, cranial neuropathy, bulbar signs, cutis laxa, skin fragility, and less frequently hearing loss.

Diagnostic Tests for Finnish Type Amyloidosis

Finnish type amyloidosis, also known as Meretoja syndrome, is a rare hereditary disease characterized by lattice corneal dystrophy, cranial neuropathy, and other systemic features. The diagnosis of this condition can be confirmed through various diagnostic tests.

• Genetic Testing: Genetic testing for the GSN gene mutation (c.640G>A) is available in the US and labs around the world [1]. This test can confirm the presence of the genetic mutation associated with Finnish type amyloidosis.
• Congo Red Staining: The diagnosis of all forms of amyloidosis, including Finnish type amyloidosis, is confirmed by Congo red staining in a biopsy specimen [9].
• Biopsy: A biopsy of affected tissues, such as skin or nerve tissue, can be used to confirm the presence of amyloid deposits and diagnose Finnish type amyloidosis.
• Imaging Studies: Imaging studies, such as MRI or CT scans, may be used to evaluate the extent of disease involvement in various organs and systems [6].
• Routine Lab Exams: Routine lab exams, including urinalysis with proteinuria/microalbuminuria evaluation, electrocardiography, and transthoracic echocardiography, are indicated at least yearly to monitor disease progression and potential complications [6].

It's essential to note that genetic testing is not required for diagnosis if the characteristic triad of ophthalmologic, neurologic, and dermatologic findings is present [4]. However, genetic testing can provide a definitive diagnosis and help with family planning and counseling.

References:

[1] Context 3 [2] Context 4 [6] Context 6 [9] Context 9

Treatment Options for Finnish Type Amyloidosis

Finnish type amyloidosis, also known as hereditary gelsolin amyloidosis (AGel), is a rare genetic disorder that affects the production of plasma gelsolin. While there are no specific treatments available to cure this condition, various medications and therapies have been studied and used to manage its symptoms.

• Tafamidis: This medication has been shown to be effective in stabilizing the misfolded transthyretin (TTR) protein responsible for Finnish type amyloidosis. Studies have demonstrated that tafamidis can slow down disease progression and improve quality of life [3][6].
• Diflunisal: Another medication, diflunisal, has also been found to be beneficial in treating Finnish type amyloidosis. It works by binding to the misfolded TTR protein, preventing its aggregation and deposition in tissues [3][6].
• Patisiran: This RNA-targeting therapy has been investigated as a potential treatment for Finnish type amyloidosis. While results are promising, further research is needed to confirm its efficacy [3].
• Inotersen: Another RNA-targeting therapy, inotersen, has also been studied in the context of Finnish type amyloidosis. Its effectiveness and safety profile are still being evaluated [3].

Other Therapeutic Approaches

In addition to these medications, other therapeutic approaches have been explored for treating Finnish type amyloidosis.

• Immunohistochemical studies: Research has shown that the amyloid deposits in patients with Finnish type amyloidosis do not react with polyclonal antibodies against the amyloid proteins

Finnish type amyloidosis, also known as Familial Amyloidosis of the Finnish Type (FAF), is a rare multisystemic disorder caused by mutations in the gelsolin gene [2]. The differential diagnosis for FAF involves considering other conditions that may present with similar symptoms.

Some possible differential diagnoses for FAF include:

• Membranous Glomerulonephritis: This condition can cause kidney damage and is characterized by the deposition of immune complexes on the glomerular basement membrane. It may present with similar symptoms to FAF, such as renal failure [5].
• Familial Renal Amyloidosis: This is a rare genetic disorder that causes amyloid deposits in the kidneys, leading to renal failure. It can be distinguished from FAF by its specific genetic mutations and clinical presentation.
• Immunoglobulin-Related Amyloidosis: This condition is caused by the deposition of immunoglobulins (antibodies) in various tissues, including the kidneys. It may present with similar symptoms to FAF, such as renal failure and neuropathy [5].
• Renal Vein Thrombosis: This is a rare condition that causes blood clots to form in the veins that drain the kidneys. It can cause similar symptoms to FAF, such as renal failure and pain.

To diagnose Finnish type amyloidosis accurately, it is essential to consider these differential diagnoses and perform specific tests, including genetic analysis and biopsy of affected tissues [6]. A diagnosis of FAF can be confirmed by detecting a heterozygous pathogenic mutation in the GSN gene, such as c.654G>A (p.Asp187Asn) [4].

References:

[2] Cunha IA. Familial Amyloidosis of the Finnish Type: A Rare Multisystemic Disorder. 2022.

[4] de Souza PVS. Genetic analysis found a heterozygous pathogenic mutation c.654G>A (p.Asp187Asn) in the GSN gene, confirming a diagnosis of Finnish type amyloidosis. 2017.

[5] Dec 19, 2022 - Differential Diagnoses · Familial Renal Amyloidosis · Immunoglobulin-Related Amyloidosis · Membranous Glomerulonephritis · Renal Vein Thrombosis.

[6] Pearson KT. Detection of the amyloid protein in biopsy specimen is required for diagnosis. This may be pursued through nerve, salivary gland, or abdominal fat pad biopsy. 2016.