Is Amyloidosis Hereditary?

Introduction: Is Amyloidosis Hereditary??

Amyloidosis is an uncommon and complex disease resulting from the deposition of abnormal protein fibrils, referred to as amyloid fibrils, in organs and tissues. This deposition disrupts regular organ function and, if untreated, can become fatal. While most types of amyloidosis do not have a genetic cause, there are some that are inherited.

This article by AmyloidosisSupport examines the inherited types of amyloidosis, the genetic and mutation factor, and what families and individuals can do to cope with the risk. If recently diagnosed or with a family history of amyloidosis, knowing about the genetic aspect is key to early diagnosis, treatment, and support.

What Is Amyloidosis?

Amyloidosis is a collection of diseases with the deposition of misfolded proteins in organs and tissues. The misfolded proteins are aggregated together and create insoluble fibrils that the body cannot degrade.

Amyloidosis exists in various forms, such as:

• AL (Light Chain) Amyloidosis – due to abnormal plasma cells (acquired)
• AA Amyloidosis – due to chronic inflammatory diseases
• ATTR (Transthyretin) Amyloidosis – due to transthyretin protein defects, which may be hereditary or age-related
• Dialysis-related Amyloidosis – in patients undergoing long-term dialysis

Let’s find out now which ones are hereditary and what role genetic mutations play.

Understanding Hereditary Amyloidosis

Hereditary amyloidosis, or familial amyloidosis, results from inherited gene mutations that result in the synthesis of unstable proteins. These unstable proteins are more prone to misfolding and aggregation into amyloid fibrils, which accumulate in tissues.

The most prevalent hereditary type is Hereditary Transthyretin Amyloidosis (hATTR), but others are rare as well. These include Apolipoprotein A-I, Fibrinogen Aα-chain, Gelsolin, and Lysozyme-related amyloidosis.

Types of Hereditary Amyloidosis

Hereditary Transthyretin Amyloidosis (HATTR)

• Gene Involved: TTR (Transthyretin)
• Mutation Type: Autosomal dominant
• Symptoms: Peripheral neuropathy, heart failure, carpal tunnel syndrome, weight loss, gastrointestinal disturbances
• Age of Onset: Usually 30–70 years, depending on the mutation

The TTR gene encodes the transthyretin protein, which serves to transport vitamin A and thyroxine. Mutations destabilize the protein and result in amyloid deposits.

Common mutations:

• Val30Met (prevalent in Portugal, Sweden, Japan)
• Val122Ile (more prevalent in African-American populations)
• Thr60Ala, Gly47Arg, and others

Fibrinogen Aα-Chain Amyloidosis

• Gene: FGA
• Organs Primarily Involved: Kidneys
• Symptoms: Nephrotic syndrome, progressive renal failure
• Inheritance: Autosomal dominant

Apolipoprotein A-I Amyloidosis

• Gene: APOA1
• Organs Involved: Liver, kidneys, GI tract
• Symptoms: Renal dysfunction, liver enlargement
• Inheritance: Autosomal dominant

Lysozyme Amyloidosis

• Gene: LYZ
• Symptoms: GI bleeding, kidney disease, liver dysfunction
• Extremely rare but of note in some families

Gelsolin Amyloidosis

• Gene: GSN
• Symptoms: Palsy of the facial nerve, lattice corneal dystrophy, skin laxity
• Region-Specific

How Is Hereditary Amyloidosis Inherited?

The majority of hereditary amyloidosis is inherited in an autosomal dominant pattern:

• If the parent who is carrying the mutated gene has a child, the child has a 50% chance of inheriting the mutated gene.
• Either males or females are equally likely to inherit the mutation.
• Having the mutation does not always guarantee that the individual will manifest symptoms (variable penetrance).

Symptoms of Hereditary Amyloidosis

Symptoms differ according to gene mutation and affected organs but may include:

• Tingling, numbness, or burning in fingers and toes
• Unexplained weight loss
• Breathlessness or tiredness due to cardiac involvement
• Kidney failure signs like swelling and frothy urine
• Diarrhea or constipation that is chronic
• Changes in vision or corneal opacities
• Carpal tunnel syndrome
• Early cardiac arrest or neurological disease family history

Symptoms can develop gradually and are usually similar to more familiar conditions, which can slow down diagnosis.

Diagnosis: How Is Hereditary Amyloidosis Identified?

Family History Evaluation

Physicians will seek a pattern of symptoms through generations, particularly unexplained nerve or heart difficulties, sudden death due to the heart from younger relatives, and several family members with amyloidosis diagnosed.

Genetic Testing

Genetic testing is the diagnostic gold standard for hereditary amyloidosis. A blood or saliva test is taken to screen for amyloid-related gene mutations.

Panels screening multiple genes or single mutations (such as Val30Met in TTR) may be done. Genetic counseling prior to and following testing is strongly advised.

Biopsy

In some instances, tissue biopsy (of fat, kidney, or nerve) may be required to identify amyloid deposits via Congo red staining.

Advanced Imaging

Cardiac MRI, echocardiography, and nuclear scans (e.g., 99mTc-PYP) can be employed to evaluate organ involvement.

What Happens If You Have a Mutation?

A positive test for a mutation doesn’t mean disease, but it does raise your risk.

If you’re a carrier:

• Start routine health surveillance (particularly cardiac and neurological)
• Report findings to close relatives for possible testing
• Discuss with experts knowledgeable about amyloidosis
• Investigate family planning choices (such as IVF with genetic screening)
• Look at enrolling in a patient registry or clinical trial

Treatment Choices for Hereditary Amyloidosis

Recent treatments are greatly enhancing results for individuals with hereditary amyloidosis.

TTR Stabilizers

Tafamidis (Vyndaqel) inhibits TTR protein from folding aberrantly and becoming amyloid fibrils. It’s particularly beneficial for patients with cardiac symptoms.

Gene Silencers

Patisiran (Onpattro) and Inotersen (Tegsedi) decrease liver production of abnormal transthyretin protein and slow the progression of disease.

Organ-Specific Care

• Pacemakers or defibrillators for cardiac problems
• Support for kidneys, including dialysis
• Physical therapy and management of neuropathy

Liver Transplantation

Once the standard for some hereditary types, it is now less often performed because new medications are so effective.

Living With Hereditary Amyloidosis: Lifestyle Tips

• Eat a heart-healthy, low-sodium diet
• Avoid smoking and alcohol
• Remain physically active, as tolerated
• Regular follow-up visits with specialists
• Support group participation in amyloidosis
• Keep current with new therapies and clinical trials

Genetic Counseling and Family Planning

Genetic counselors are essential in:

• Interpreting test results
• Facilitating family communication
• Decision-making regarding having children
• Coping with emotional and psychological effects

For carriers seeking to have children, options include preimplantation genetic testing and other reproductive strategies.

Real Story: John’s Journey

John, a 45-year-old man with unexplained neuropathy and a family history of heart failure, was finally diagnosed with hATTR due to Val122Ile mutation. With early genetic diagnosis and support from his health care providers, he initiated therapy with Tafamidis and instituted lifestyle modifications. His 21-year-old daughter was predictive genetically tested. The genetic diagnosis at an early stage helped John achieve stabilization of his health and educated his family on how to take action early.

Frequently Asked Questions

Is amyloidosis always hereditary?
No. AL and AA amyloidosis are not hereditary. Only specific forms, especially hATTR, are inherited.

Can children be tested for the gene?
Yes, though typically adults (18+) are tested unless symptoms are present or parents decide after counseling.

Does having the gene mean I’ll get the disease?
Not necessarily. Many carriers never develop symptoms. Regular monitoring is essential.

Is there a cure for hereditary amyloidosis?
No cure exists, but disease-modifying therapy is available to slow the rate of progression and enhance quality of life.

Final Thoughts

Knowing if amyloidosis is inherited can empower families and patients to take early steps, receive proper treatment, and make informed choices. If you suspect a family connection, don’t wait to contact a geneticist or amyloidosis specialist.

We’re here at AmyloidosisSupport to assist with:

• Accurate, current medical information
• Community resources and support
• Referrals to specialists
• Patient advocacy and awareness campaigns

Your genes are not your destiny. Knowledge, early action, and support can make a difference.

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