Primary systemic amyloidosis

General Information (adopted from Orphanet):

Synonyms, Signs: PSA [IBIS]
AL Amyloidosis, included
Systemic immunoglobulinic amyloidosis
AL, included
Systemic AL amyloidosis
Number of Symptoms 36
OrphanetNr: 314701
OMIM Id: 254500
ICD-10: E85.0
E85.1
E85.2
E85.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: AL amyloidosis
 -Rare cardiac disease
 -Rare genetic disease
 -Rare hematologic disease
 -Rare neurologic disease
 -Rare oncologic disease
 -Rare renal disease
 -Rare systemic or rheumatologic disease

Comment:

Annotated subdisease of AL amyloidosis (Disease:6857, Orphanet:85443) The most common subset of the amyloidoses is primary systemic amyloidosis (AL), with approximately 2,000-2,500 new cases occurring each year in the United States (PMID:23337445). Clinically significant cardiac involvement manifests in approximately one-third to one-half of AL patients, with a substantial proportion only discovered on biopsy or autopsy. The predominant symptom is rapidly progressive diastolic heart failure with preserved ejection fraction, which, when present, is the most influential prognostic factor (PMID:23337445). Primary systemic amyloidosis (PSA) is also called Lubarsch-Pick disease (PMID:26390868).

Symptom Information: Sort by abundance 

1
(HPO:0012597) Heavy proteinuria Frequent [IBIS] 23337445 IBIS 2 / 7739
2
(HPO:0200097) Oral mucosal blisters Rare [IBIS] 26708800 IBIS 7 / 7739
3
(HPO:0002321) Vertigo Rare [IBIS] 11705429 IBIS 58 / 7739
4
(HPO:0003473) Fatigable weakness 26390868 IBIS 39 / 7739
5
(HPO:0012280) Hepatic amyloidosis 17093068 IBIS 4 / 7739
6
(HPO:0002014) Diarrhea Rare [IBIS] 11705429 IBIS 225 / 7739
7
(HPO:0002039) Anorexia Rare [IBIS] 11705429 IBIS 62 / 7739
8
(HPO:0002024) Malabsorption Rare [IBIS] 11705429 IBIS 142 / 7739
9
(HPO:0002570) Steatorrhea Rare [IBIS] 11705429 IBIS 31 / 7739
10
(HPO:0001824) Weight loss 11705429 IBIS 42 / 7739
11
(HPO:0000979) Purpura Rare [IBIS] 26708800 IBIS 27 / 7739
12
(HPO:0001030) Fragile skin Rare [IBIS] 26390868 IBIS 25 / 7739
13
(HPO:0000967) Petechiae Rare [IBIS] 26390868 IBIS 26 / 7739
14
(HPO:0001638) Cardiomyopathy 23337445 IBIS 192 / 7739
15
(HPO:0001279) Syncope 23337445 IBIS 94 / 7739
16
(HPO:0001677) Coronary artery disease 23337445 IBIS 58 / 7739
17
(HPO:0001644) Dilated cardiomyopathy 23337445 IBIS 141 / 7739
18
(HPO:0002615) Hypotension 11705429 IBIS 52 / 7739
19
(HPO:0011675) Arrhythmia 23337445 IBIS 226 / 7739
20
(HPO:0006775) Multiple myeloma 16107109 IBIS 10 / 7739
21
(HPO:0003073) Hypoalbuminemia Frequent [IBIS] 23337445 IBIS 40 / 7739
22
(HPO:0011034) Amyloidosis Very frequent [IBIS] 17093068 IBIS 12 / 7739
23
(OMIM) Paraproteinemia 18708629 IBIS 3 / 7739
24
(MedDRA:10048620) Intracardiac thrombus 23337445 IBIS 2 / 7739
25
(MedDRA:10060880) Monoclonal gammopathy 18708629 IBIS 5 / 7739
26
(MedDRA:10006513) Bruising, ecchymosis and purpura 26390868 IBIS 3 / 7739
27
(MedDRA:10052337) Diastolic dysfunction Frequent [IBIS] 23337445 IBIS 14 / 7739
28
(OMIM) Primary immunoglobulin-related amyloidosis (AL) 16107109 IBIS 3 / 7739
29
(MedDRA:10036673) Primary amyloidosis 26708800 IBIS 3 / 7739
30
(MedDRA:10005372) Blood blister Rare [IBIS] 26708800 IBIS 2 / 7739
31
(OMIM) High M-component 18708629 IBIS 3 / 7739
32
(MedDRA:10059245) Angiopathy 23337445 IBIS 3 / 7739
33
(HPO:0030150) Plasmacytosis 26390868 IBIS 3 / 7739
34
(HPO:0030156) Bence Jones Proteinuria Frequent [IBIS] 23337445 IBIS 2 / 7739
35
(MedDRA:10007509) Cardiac amyloidosis 16107109 IBIS 5 / 7739
36
(MedDRA:10059250) Gastrointestinal amyloidosis 17093068 IBIS 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
FGFR3 rs121913482 pathogenic RCV000017732.4
FGFR3 rs78311289 pathogenic RCV000017729.4

Additional Information:

Description: (OMIM) Multiple myeloma is a neoplastic plasma cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment, monoclonal protein in the blood or urine, and associated organ dysfunction (Palumbo and Anderson, 2011).
Clinical Description OMIM Leoncini and Korngold (1964) described multiple myeloma in 2 sisters and reviewed the literature on familial cases. Manson (1961) reported affected sisters, one of whom also had pernicious anemia. Myeloma has also been observed in father and son ...
Molecular genetics OMIM Shaffer et al. (2008) used a loss-of-function, RNA interference-based genetic screen to demonstrate that inhibition of IRF4 (601900) is toxic to myeloma cell lines, regardless of transforming oncogenic mechanism. Gene expression profiling and genomewide chromatin immunoprecipitation analysis uncovered ...