Lysozyme amyloid related amyloidosis
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Synonyms and keywords:Lysozyme amyloidosis, ALys, Hereditory amyloidosis, autosomal dominant amyloidosis, Hereditary lysozyme amyloidosis, Familial amyloid nephropathy due to lysozyme variant, Familial renal amyloidosis due to lysozyme variant, Hereditary amyloid nephropathy due to lysozyme variant, Hereditary renal amyloidosis due to lysozyme variant

# Overview
Lysozyme amyloid related amyloidosis is one of the subtypes of familial amyloidosis, it is associated with four mutations include, Ile56Thr, Asp67His, Trp64Arg, and Phe57Ile. It is an extremely rare disease and it commonly affects individuals in their third to fourth decades of life. Manifestation of the disease are based on which organs are involved, and include GI symptoms, renal impairment, sicca syndrome, lymphadenopathy, splenomegaly, and petechiae or purpura. The diagnosis of lysozyme amyloid related amyloidosis is based on the family history, histologic examination and amino acid sequencing. There is no treatment for lysozyme amyloid related amyloidosis; the mainstay of therapy is supportive care. Organ transplant could be done as palliative treatment.

# 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.
- In 1993, Pepys introduced that lysozyme form as an an amyloid fibril protein is a variant of hereditary systemic amyloidosis.

# Classification
Lysozyme amyloid related amyloidosis is one of the subtypes of familial amyloidosis. Familiar amyloidosis may be classified according to the type of mutant protein into 6 subtypes:
- Transthyretin (TTR)
- Apolipoprotein AI
- Apolipoprotein AII
- Fibrinogen Aa
- Lysozyme
- Gelsolin
- Cystatin C

# Pathophysiology
- 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.

## Genetics
There are four genetic mutations which are associated with lysozyme amyloid related amyloidosis. include:
- Ile56Thr
- Asp67His
- Trp64Arg
- Phe57Ile

# Causes
Common cause of lysozyme amyloid related amyloidosis is genetic mutations.

# Differentiating lysozyme amyloid related amyloidosis from Other Diseases
Lysozyme amyloid related amyloidosis must be differentiated from other types of familial amyloidosis and other diseases that mimic amyloidosis and may present as organ dysfunction, specifically, nephrotic syndrome leading to renal failure, cardiac failure and polyneuropathy.
For more information on the differential diagnosis of lysozyme amyloid related amyloidosis click here

# 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.
- Lysozyme amyloid related amyloidosis commonly affects individuals in their third to fourth decades of life.
- 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
The most potent risk factor in the development of lysozyme amyloid related amyloidosis is positive familial history. Other risk factors include older age, male gender, and African-American race.

# Screening
There is insufficient evidence to recommend routine screening for lysozyme amyloid related amyloidosis.

# Natural History, Complications, and Prognosis
- Important complication of lysozyme amyloid related amyloidosis is  heavy bleeding caused by hepatic rupture and/or hemorrhagic lymph node rupture.
Note: Because the risk of bleeding in this patients, liver biopsy should not be performed in suspected ones.

# Diagnosis

## Diagnostic Study of Choice
- The diagnosis of lysozyme amyloid related amyloidosis is based on the family history, histologic examination and amino acid sequencing.

## History and Symptoms
- Common symptoms of lysozyme amyloid related amyloidosis include fatigue, weight loss and, edema.
- Other symptoms of lysozyme amyloid related amyloidosis include sicca, diarrhea, nausea, abdominal discomfort, GI bleeding, worsening kidney function.

## Physical Examination
Physical examination of patients with lysozyme amyloid related amyloidosis is usually remarkable for renal impairment, petechiae, purpura, lymphadenopathy, and splenomegaly.

## 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.

## Electrocardiogram
Although, cardiac involvement is so rare in lysozyme amyloid related amyloidosis, electrocardiography may be done for cardiac analysis..

## X-ray
There are no x-ray findings associated with lysozyme amyloid related amyloidosis.

## Echocardiography or Ultrasound
Although, cardiac involvement is so rare in lysozyme amyloid related amyloidosis, echocardiography may be done for cardiac analysis.

## CT scan
There are no CT scan findings associated with lysozyme amyloid related amyloidosis.

## MRI
There are no MRI findings associated with lysozyme amyloid related amyloidosis.

## Other Imaging Findings
Total body SAP component scintigraphy may be helpful in the diagnosis of lysozyme amyloid related amyloidosis. It can show lysozyme amyloid deposition and extension of it in the liver, spleen, kidney, adrenal glands, and bone marrow.

## Other Diagnostic Studies
- Tissue biopsy with Congo red stain is diagnostic for lysozyme amyloid related amyloidosis.
- Biopsy of tissue may be taken from an affected organ like kidney,  subcutaneous fat, digestive tract, or labial salivary glands.
- Immunohistochemistry using a polyclonal antibody against lysozyme is also used in diagnosis of the disease.
- Direct in vitro amino acid sequencing for typing of amyloid fibril proteins is the definite technique for diagnosis of  lysozyme amyloid related amyloidosis.

# Treatment

## Medical Therapy
There is no treatment for lysozyme amyloid related amyloidosis; the mainstay of therapy is supportive care.

## Surgery
- Kidney transplant may be effective in patients with minor or absent extrarenal visceral involvement.
- Liver transplant may be used as a palliative treatment.

## Primary Prevention
There are no established measures for the primary prevention of lysozyme amyloid related amyloidosis.

## Secondary Prevention
Effective measures for the secondary prevention of lysozyme amyloid related amyloidosis include:
- History and physical examination
- Electrocardiogram for cardiac examination