Leucocyte cell-derived chemotaxin 2 related amyloidosis: Difference between revisions
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==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
* Patient survival in ALECT2 amyloidosis is significantly better than that of AL amyloidosis and AA amyloidosis, likely because of the rarity or absence of cardiac involvement in ALECT2 amyloidosis. | |||
* In a series of 72 patients with renal ALECT2 amyloidosis, only 6% of 64 patients with available data died after a median follow-up of 22 months. | |||
* The renal survival, however, is guarded; 39% of patients in the above-mentioned study progressed to ESRD . | |||
* Independent predictors of renal survival in renal ALECT2 amyloidosis without concurrent kidney disease on biopsy were serum creatinine at diagnosis, with a value of 2.0 mg/dl being the best cutoff for predicting ESRD, degree of glomerulosclerosis, and presence of diabetes | |||
* Renal amyloid load and degree of proteinuria did not predict outcome | |||
==Diagnosis== | ==Diagnosis== | ||
| Line 84: | Line 90: | ||
==Treatment== | ==Treatment== | ||
===Medical Therapy=== | ===Medical Therapy=== | ||
Revision as of 17:11, 30 October 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]
Synonyms and keywords:LECT2 amyloidosis
Overview
Historical Perspective
- The first case of ALECT2 was discovered by Benson et al in 2008.
Classification
Pathophysiology
- The pathogenesis of this disease is related to accumulation of a protein called LECT2.
- LECT2 protein is a multi functional factor involved in
- Chemotaxis
- Inflammation
- Immunomodulation
- Damage/repair process.
- LECT2 is synthesized mainly by hepatocytes but also expressed in many organs, including vascular endothelial cells, smooth muscle cells, adipocytes, and epithelial cells such as renal tubular epithelial cells.
- According to the literature, ALECT2 involves G/A polymorphism affecting nucleotide 172 in exon 3 of the LECT2 protein.
- Substitution of the isoleucine with valine at position 40 makes the protein unstable imparting an amyloidogenic property to the LECT2 protein.
- Alternately the disease could be due to interference in the LECT2 catabolic pathway or LECT2 transport.
- Possibly resulting from a genetic defect which ultimately results in an increased local tissue concentration of LECT2 leading to amyloid fibril formation.
- The kidney is the primary target of this disease. '
- Other common organs involved other than the kidney include liver, spleen, prostate, gastrointestinal tract, peripheral nervous system, and lungs.
- Cardiac involvement never occurs, which gives this disease a survival advantage compared to other forms of amyloidosis.
- Other organs which are not involved include brain, pancreas, and fibroadipose tissue.
| Unidentified Genetic Mutation | Hepatocelluar Damage | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| LECT2 overexpression by hepatocytes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Misfolded LECT2 protein | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Increased local concentrations Interactions with components of extracellular matrix, such as laminin and type IV collagen Bindings with serum amyloid P (SAP) apoE, and glycosaminoglycans (GAGs) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Amyloid fibril formation and stabilization. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ALECT2 amyloidosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Causes
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
- Patient survival in ALECT2 amyloidosis is significantly better than that of AL amyloidosis and AA amyloidosis, likely because of the rarity or absence of cardiac involvement in ALECT2 amyloidosis.
- In a series of 72 patients with renal ALECT2 amyloidosis, only 6% of 64 patients with available data died after a median follow-up of 22 months.
- The renal survival, however, is guarded; 39% of patients in the above-mentioned study progressed to ESRD .
- Independent predictors of renal survival in renal ALECT2 amyloidosis without concurrent kidney disease on biopsy were serum creatinine at diagnosis, with a value of 2.0 mg/dl being the best cutoff for predicting ESRD, degree of glomerulosclerosis, and presence of diabetes
- Renal amyloid load and degree of proteinuria did not predict outcome