Apolipoprotein AI amyloidosis
Synonyms and keywords:

# Overview

# Historical Perspective
- In 1639, Nicolaus Fontanus autopsied a young man who had ascites, jaundice, liver abscess, and splenomegaly and his report has been the first description of amyloidosis.
- In 1854, Rudolph Virchow introduced the term "amyloid" as a macroscopic abnormality in some tissues.
- In 1867, Weber reported the first case of amyloidosis associated with multiple myeloma.
- In 1922, Bennhold introduced Congo Red staining of amyloid that remains the gold standard for diagnosis.
- In 1959, Cohen and Calkins used ultrathin sections of amyloidotic tissues and assessed by electron microscopy, explained the presence of non-branching fibrils with indeterminate length and variable width.

# Classification
Apolipoprotein AI amyloidosis is one of the subtypes of familial amyloidosis. Familiar amyloidosis may be classified according to the type of mutant protein into 7 subtypes:
- Transthyretin (TTR)
- Apolipoprotein AI
- Apolipoprotein AII
- Fibrinogen Aa
- Lysozyme
- Gelsolin
- Cystatin C

# Pathophysiology

## Pathogenesis
- It is understood that amyloidosis is the result of deposition of Amyloid.
- Amyloid is an abnormal insoluble extracellular protein which may cause organic dysfunction and a wide variety of clinical syndromes.
- These abnormal amyloids are derived from misfolding and aggregation of normally soluble proteins.
- Amyloid depositions also have glycosaminoglycans and serum amyloid P component (SAP) which alter the propensity for amyloid formation.
- Amyloid deposition can disrupt tissue structure of involved organ and consequently leads to organ failure.
- Genetic mutations in Apolipoprotein AI gene may lead to misfolding protein product.

## Genetics
- Single nucleotide substitutions in apolipoprotein AI gene.
- The underlying pathogenesis is incomplete degradation of this protein in body.
- The mode of inheritance in autosomal dominant with different penetrance.

# Causes
Common cause of Apolipoprotein AI amyloidosis is genetic mutation.

# Differentiating Apolipoprotein AI amyloidosis from Other Diseases

# Epidemiology and Demographics
- The incidence of amyloidosis is approximately 1.2 per 100,000 individuals per year worldwide.
- The mortality rate of systemic amyloidosis is approximately 100 per 100,000 deaths in developed countries.
- Apolipoprotein AI amyloidosis commonly affects individuals older than 30.
- Hereditary amyloidosis subtypes include a substitution of an amino acid that is detected in approximately 4% of the african american population.
- Men are more commonly affected by amyloidosis than women.

# Risk Factors
- Common risk factors in the development of apolipoprotein AI amyloidosis include:
Older age
Male gender
African american race
Positive family history
- Older age
- Male gender
- African american race
- Positive family history

# Screening
There is insufficient evidence to recommend routine screening for apolipoprotein AI amyloidosis.

# Natural History, Complications, and Prognosis

# Diagnosis

## Diagnostic Study of Choice
- Tissue biopsy with Congo red stain is the gold standard test for the diagnosis of apolipoprotein AI amyloidosis.
- Biopsy tissue may be taken from an affected organ like kidney, or from subcutaneous fat or rectal mucosa.
- The rectal mucosa biopsy is more sensitive for apolipoprotein AI amyloidosis.
- Biopsy of the affected organ is recommended for patients with limited organ involvement.
- Biopsy from unaffected organs is more sensitive in patients with multi-organ involvement.
- The following finding on performing tissue biopsy is confirmatory for familial amyloidosis:
Apple green birefringence of the tissue sample under polarized light with Congo red stain.
- Apple green birefringence of the tissue sample under polarized light with Congo red stain.
- There are no established criteria for the diagnosis of familial amyloidosis.

## History and Symptoms
- Patients with apolipoprotein AI amyloidosis may have a positive history of dyspnea, lethargy, weight loss, chest discomfort, fevers or chills, night sweats, positive family history of amyloidosis, male gender, and african american race
- Common symptoms of apolipoprotein AI amyloidosis include parasthesia, edema, cutaneous lesions, hoarseness, and cough
- Less common symptoms of apolipoprotein AI amyloidosis include hoarseness, gastrointestinal bleeding, diarrhea, paresthesias, gross hematuria, and irritative urinary symptoms

## Physical Examination
Physical examination of patients with apolipoprotein AI amyloidosis is usually remarkable for sensory and motor neuropathy, edema, and cutaneous lesion.

## Laboratory Findings
- Common tests that are abnormal in liver function tests including AST, ALT, total bilirubin, alkaline phosphatase, and albumin.
- Common tests that are abnormal in renal function tests including serum creatinine, urinary protein, glomerular filtration rate, and albumin to creatinine ratio in the urine.
- Cardiac biomarkers such as troponin and BNP and are the most important predictors of outcome in amyloidosis. They provide a quantitative assessment for cardiac damage and wall strain.

## Electrocardiogram
- Findings on an ECG suggestive of apolipoprotein AI amyloidosis include low voltage in the limb leads, AV block, atrial fibrillation, heart block, and angina or infarction

## X-ray
- There are no x-ray findings associated with apolipoprotein AI amyloidosis.

## Echocardiography or Ultrasound
- Findings on echocardiography suggestive of apolipoprotein AI amyloidosis include:
Sparkling or speckled appearance of the left ventricular thickening
Hypertrophied right ventricle
Diastolic dysfunction with restrictive filling pattern (in the advanced stages)
Severe atrial dilatation
Thickening of the interatrial septum
Pericardial effusion
Prominent valves
- Sparkling or speckled appearance of the left ventricular thickening
- Hypertrophied right ventricle
- Diastolic dysfunction with restrictive filling pattern (in the advanced stages)
- Severe atrial dilatation
- Thickening of the interatrial septum
- Pericardial effusion
- Prominent valves

## CT scan

## MRI

## Other Imaging Findings
There are no other imaging findings associated with apolipoprotein AI amyloidosis.

## Other Diagnostic Studies
There are no other diagnostic studies associated with apolipoprotein AI amyloidosis.

# Treatment

## Medical Therapy
There is no medical therapy for apolipoprotein AI amyloidosis. The mainstay of therapy is supportive care.

## Surgery
- Cardiac transplant may need to be done for patients with cardiac amyloidosis.
- Organ-specific transplant may need to be done, depending on the organ involved.

## Primary Prevention
There is no role for primaryprevention in apolipoprotein AI amyloidosis.

## Secondary Prevention
There is no role for secondary prevention in apolipoprotein AI amyloidosis.