AL amyloidosis

General Information (adopted from Orphanet):

Synonyms, Signs: AL amyloidosis, included
Primary amyloidosis
AL, included
Immunoglobulinic amyloidosis
Light-chain amyloidosis
Number of Symptoms 86
OrphanetNr: 85443
OMIM Id: 254500
ICD-10: E85.8
UMLs: C0268381
MeSH: C531616
MedDRA: 10036673
Snomed: 23132008

Prevalence, inheritance and age of onset:

Prevalence: > 10 of 100 000
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Acquired amyloid peripheral neuropathy
 -Rare neurologic disease
Amyloidosis
 -Rare systemic or rheumatologic disease
Plasma cell tumor
 -Rare hematologic disease
 -Rare oncologic disease
Rare familial disorder with hypertrophic cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Secondary glomerular disease
 -Rare renal disease

Comment:

(Includes symptoms of the subdisease Primary systemic amyloidosis Disease:4651, Orphanet:314701 and of the subdisease Primary localized amyloidosis Disease:4652, Orphanet:314709). AL amyloidosis is caused by misfolding, aggregation and deposition of certain monoclonal immunoglobulin (Ig) light chains as extracellular insoluble fibrillar deposits that stain with Congo red and produce pathognomonic red-green birefringence when viewed in cross-polarized light. The age-adjusted incidence of AL amyloidosis is 5.1 to 12.8 per million patient years, and it is usually associated with very subtle clonal plasma cell dyscrasias that are usually best monitored by the very sensitive serum free light chain (FLC) assay (PMID:18708629). Immunoglobulin (AL) amyloidosis includes primary amyloidosis, multiple myeloma, and other plasma cell dyscrasias such as B-cell lymphoma and Waldenström macroglobulinemia. Primary amyloidosis is a plasma cell disorder in which approximately 5% to 10% of bone marrow plasma cells have clonal dominance of a light chain isotype. The number of plasma cells and the degree of clonality and marrow infiltration of those cells have been inversely related to survival. Generally, immunoglobulin variable region genes influence clinical presentation and outcome in light chain-associated amyloidosis, with a predominance of lambda versus kappa free light chains (3:1) in primary AL amyloidosis. In comparison, other plasma cell dyscrasias, such as multiple myeloma, usually have a lambda-to-kappa ratio of 1:2. The light chain isotype in primary amyloidosis does not generally affect survival. Immunoglobulin amyloidosis constitutes about 85% of all newly diagnosed cases of amyloidosis. Common presenting features include nephrotic syndrome, sensorimotor peripheral neuropathy, hepatomegaly, splenomegaly, and, less often, macroglossia (PMID:16107109).

Symptom Information: Sort by abundance 

1
 (HPO:0000100) Nephrotic syndrome Frequent [IBIS] 16107109 IBIS 83 / 7739
2
 (HPO:0000790) Hematuria 24693509 IBIS 106 / 7739
3
 (HPO:0010944) Abnormality of the renal pelvis 1632328 IBIS 3 / 7739
4
 (HPO:0000119) Abnormality of the genitourinary system 24693509 IBIS 34 / 7739
5
 (HPO:0012597) Heavy proteinuria 23337445 IBIS 2 / 7739
6
 (HPO:0200097) Oral mucosal blisters 26708800 IBIS 7 / 7739
7
 (HPO:0010288) Abnormality of the sublingual glands 9745189 IBIS 2 / 7739
8
 (HPO:0000458) Anosmia 21571465 IBIS 49 / 7739
9
 (HPO:0000421) Epistaxis 21571465 IBIS 85 / 7739
10
 (HPO:0000174) Abnormality of the palate 267888 IBIS 298 / 7739
11
 (HPO:0000520) Proptosis 22184002 IBIS 192 / 7739
12
 (HPO:0000492) Abnormality of the eyelid 8464207 IBIS 41 / 7739
13
 (HPO:0000158) Macroglossia Occasional [IBIS] 16107109 IBIS 119 / 7739
14
 (HPO:0000502) Abnormality of the conjunctiva 8464207 IBIS 6 / 7739
15
 (HPO:0000602) Ophthalmoplegia 22184002 IBIS 56 / 7739
16
 (HPO:0011482) Abnormality of the lacrimal gland 19861750 IBIS 2 / 7739
17
 (HPO:0002321) Vertigo 11705429 IBIS 58 / 7739
18
 (HPO:0007141) Sensorimotor neuropathy Frequent [IBIS] 16107109 IBIS 27 / 7739
19
 (HPO:0003473) Fatigable weakness 26390868 IBIS 39 / 7739
20
 (HPO:0002832) Calcific stippling 17704307 IBIS 5 / 7739
21
 (HPO:0002039) Anorexia 11705429 IBIS 62 / 7739
22
 (HPO:0001744) Splenomegaly Frequent [IBIS] 16107109 IBIS 337 / 7739
23
 (HPO:0002240) Hepatomegaly Frequent [IBIS] 16107109 IBIS 467 / 7739
24
 (HPO:0012280) Hepatic amyloidosis 17093068 IBIS 4 / 7739
25
 (HPO:0002570) Steatorrhea 11705429 IBIS 31 / 7739
26
 (HPO:0002024) Malabsorption 11705429 IBIS 142 / 7739
27
 (HPO:0002014) Diarrhea 11705429 IBIS 225 / 7739
28
 (HPO:0001824) Weight loss 11705429 IBIS 42 / 7739
29
 (HPO:0009098) Chronic oral candidiasis 25586447 IBIS 5 / 7739
30
 (HPO:0000979) Purpura 26708800 IBIS 27 / 7739
31
 (HPO:0001030) Fragile skin 26390868 IBIS 25 / 7739
32
 (HPO:0200044) Porokeratosis 17397946 IBIS 11 / 7739
33
 (HPO:0000967) Petechiae 26390868 IBIS 26 / 7739
34
 (HPO:0002615) Hypotension 11705429 IBIS 52 / 7739
35
 (HPO:0001279) Syncope 23337445 IBIS 94 / 7739
36
 (HPO:0001635) Congestive heart failure 16107109 IBIS 232 / 7739
37
 (HPO:0001638) Cardiomyopathy 23337445 IBIS 192 / 7739
38
 (HPO:0003116) Abnormal echocardiogram 16107109 IBIS 33 / 7739
39
 (HPO:0001644) Dilated cardiomyopathy 23337445 IBIS 141 / 7739
40
 (HPO:0001645) Sudden cardiac death 16107109 IBIS 84 / 7739
41
 (HPO:0001698) Pericardial effusion 16107109 IBIS 20 / 7739
42
 (HPO:0001677) Coronary artery disease 23337445 IBIS 58 / 7739
43
 (HPO:0005110) Atrial fibrillation 16107109 IBIS 71 / 7739
44
 (HPO:0011675) Arrhythmia 16107109 IBIS 226 / 7739
45
 (HPO:0001685) Myocardial fibrosis 16107109 IBIS 30 / 7739
46
 (HPO:0006775) Multiple myeloma Frequent [IBIS] 16107109 IBIS 10 / 7739
47
 (HPO:0012191) B-cell lymphoma 17244928 IBIS 5 / 7739
48
 (HPO:0011034) Amyloidosis Very frequent [IBIS] 17093068 IBIS 12 / 7739
49
 (HPO:0003073) Hypoalbuminemia 23337445 IBIS 40 / 7739
50
 (HPO:0002778) Abnormality of the trachea 21571465 IBIS 3 / 7739
51
 (HPO:0100721) Mediastinal lymphadenopathy 17704307 IBIS 19 / 7739
52
 (HPO:0030156) Bence Jones Proteinuria 23337445 IBIS 2 / 7739
53
 (IBIS) Penile primary localized amyloidosis 17645099 IBIS 2 / 7739
54
 (IBIS) Stippled calcification in the right supraclavicular area and mediastinum 17704307 IBIS 2 / 7739
55
 (IBIS) Duodenal primary localized amyloidosis 17296522 IBIS 2 / 7739
56
 (IBIS) Nasopharyngeal primary localized amyloidosis 23978123 IBIS 2 / 7739
57
 (IBIS) Nasal primary localized amyloidosis 21571465 IBIS 2 / 7739
58
 (MedDRA:10063945) Pulmonary amyloidosis 17244928 IBIS 2 / 7739
59
 (IBIS) Facial pain 21571465 IBIS 2 / 7739
60
 (IBIS) Oropharyngeal primary localized amyloidosis 23978123 IBIS 2 / 7739
61
 (MedDRA:10059250) Gastrointestinal amyloidosis 17093068 IBIS 2 / 7739
62
 (IBIS) Lacrimal gland primary localized amyloidosis 19861750 IBIS 2 / 7739
63
 (OMIM) Primary immunoglobulin-related amyloidosis (AL) 16107109 IBIS 3 / 7739
64
 (IBIS) Thoracic primary localized amyloidosis 17704307 IBIS 2 / 7739
65
 (MedDRA:10007509) Cardiac amyloidosis Frequent [IBIS] 16107109; 10659664 IBIS 5 / 7739
66
 (HPO:0012716) Moderate conductive hearing impairment 21571465 IBIS 2 / 7739
67
 (MedDRA:10052337) Diastolic dysfunction 23337445 IBIS 14 / 7739
68
 (IBIS) Oral primary localized amyloidosis 25586447 IBIS 2 / 7739
69
 (MedDRA:10013002) Dilatation atrial 16107109 IBIS 1 / 7739
70
 (OMIM) Paraproteinemia 18708629 IBIS 3 / 7739
71
 (HPO:0030150) Plasmacytosis 26390868 IBIS 3 / 7739
72
 (MedDRA:10005372) Blood blister 26708800 IBIS 2 / 7739
73
 (IBIS) Urogenital primary localized amyloidosis 24693509 IBIS 2 / 7739
74
 (MedDRA:10006513) Bruising, ecchymosis and purpura 26390868 IBIS 3 / 7739
75
 (MedDRA:10036673) Primary amyloidosis 26708800 IBIS 3 / 7739
76
 (IBIS) Orbital primary localized amyloidosis 22184002 IBIS 2 / 7739
77
 (IBIS) Pulmonary primary localized amyloidosis 17244928 IBIS 2 / 7739
78
 (OMIM) Poor R-wave progression on electrocardiogram 16107109 IBIS 2 / 7739
79
 (MedDRA:10059245) Angiopathy 23337445 IBIS 3 / 7739
80
 (MedDRA:10030983) Oral lichen planus 25586447 IBIS 2 / 7739
81
 (MedDRA:10026865) Mass 22184002 IBIS 2 / 7739
82
 (MedDRA:10047240) Venous pressure jugular increased 16107109 IBIS 6 / 7739
83
 (IBIS) Ureteric primary localized amyloidosis 22020852 IBIS 2 / 7739
84
 (OMIM) High M-component 18708629 IBIS 3 / 7739
85
 (MedDRA:10060880) Monoclonal gammopathy 18708629 IBIS 5 / 7739
86
 (MedDRA:10048620) Intracardiac thrombus 23337445 IBIS 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

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 ...