MCID: FRB001
MIFTS: 47

Farber Lipogranulomatosis

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Skin diseases, Metabolic diseases

Aliases & Classifications for Farber Lipogranulomatosis

MalaCards integrated aliases for Farber Lipogranulomatosis:

Name: Farber Lipogranulomatosis 54 12 50 24 25 56 71 13 42 14 69
Acid Ceramidase Deficiency 12 50 24 25 56 71
Farber Disease 12 50 24 25 56 71
Ceramidase Deficiency 50 25 51 71
N-Laurylsphingosine Deacylase Deficiency 12 50 71
Farber's Disease 50 25 51
Ac Deficiency 50 25 71
Farber's Lipogranulomatosis 25 29
Acylsphingosine Deacylase Deficiency 25
Farber-Uzman Syndrome 25
Frbrl 71

Characteristics:

Orphanet epidemiological data:

56
farber disease
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide),<1/1000000 (Europe); Age of onset: Antenatal,Childhood,Infancy,Neonatal; Age of death: early childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
early death (in some patients)
onset in infancy or first years of life


HPO:

32
farber lipogranulomatosis:
Onset and clinical course variable expressivity progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Farber Lipogranulomatosis

NINDS : 51 Farber’s disease, also known as Farber's lipogranulomatosis, describes a group of inherited metabolic disorders called lipid storage diseases, in which excess amounts of lipids (oils, fatty acids, and related compounds) build up to harmful levels in the joints, tissues, and central nervous system.  The liver, heart, and kidneys may also be affected.  Disease onset is typically seen in early infancy but may occur later in life.  Symptoms of the classic form  may have moderately impaired mental ability and difficulty with swallowing.  Other symptoms may include chronic shortening of muscles or tendons around joints. arthritis, swollen lymph nodes and joints, hoarseness, nodules under the skin (and sometimes in the lungs and other parts of the body), and vomiting.  Affected persons may require the insertion of a breathing tube.  In severe cases, the liver and spleen are enlarged.  Farber's disease is caused by a deficiency of the enzyme ceramidase. The disease occurs when both parents carry and pass on the defective gene that regulates the protein sphingomyelin.  Children born to these parents have a 25 percent chance of inheriting the disorder and a 50 percent chance of carrying the faulty gene.  The disorder affects both males and females.

MalaCards based summary : Farber Lipogranulomatosis, also known as acid ceramidase deficiency, is related to spinal muscular atrophy with progressive myoclonic epilepsy and lipogranulomatosis, and has symptoms including short stature, failure to thrive and nystagmus. An important gene associated with Farber Lipogranulomatosis is ASAH1 (N-Acylsphingosine Amidohydrolase 1), and among its related pathways/superpathways are Sphingolipid metabolism and Sphingolipid signaling pathway. The drugs Lenalidomide and Angiogenesis Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include liver, skin and spleen.

NIH Rare Diseases : 50 farber's disease is an inherited condition involving the breakdown and use of fats in the body (lipid metabolism). people with this condition have an abnormal accumulation of lipids (fat) throughout the cells and tissues of the body, particularly around the joints. farber's disease is characterized by three classic symptoms: a hoarse voice or weak cry, small lumps of fat under the skin and in other tissues (lipogranulomas), and swollen and painful joints. other symptoms may include difficulty breathing, an enlarged liver and spleen (hepatosplenomegaly), and developmental delay. researchers have described seven types of farber's disease based on their characteristic features. this condition is caused by mutations in the asah1 gene and is inherited in an autosomal recessive manner.       last updated: 10/8/2014

UniProtKB/Swiss-Prot : 71 Farber lipogranulomatosis: An autosomal recessive lysosomal storage disorder characterized by subcutaneous lipid-loaded nodules, excruciating pain in the joints and extremities, and marked accumulation of ceramide in lysosomes. Disease severity is variable. The most severe disease subtype is a rare neonatal form with death occurring before 1 year of age.

Genetics Home Reference : 25 Farber lipogranulomatosis is a rare inherited condition involving the breakdown and use of fats in the body (lipid metabolism). In affected individuals, lipids accumulate abnormally in cells and tissues throughout the body, particularly around the joints.

OMIM : 54
Farber lipogranulomatosis is an autosomal recessive lysosomal storage disorder characterized by early-onset subcutaneous nodules, painful and progressively deformed joints, and hoarseness by laryngeal involvement. Based on the age of onset, the severity of symptoms, and the difference in organs affected, 6 clinical subtypes due to deficiency of acid ceramidase have been distinguished. The most severe form is subtype 4, a rare neonatal form of the disease with death occurring before 1 year of age (summary by Alves et al., 2013). (228000)

Wikipedia : 72 Farber disease (also known as Farber\'s lipogranulomatosis, ceramidase deficiency, \"Fibrocytic... more...

Related Diseases for Farber Lipogranulomatosis

Diseases related to Farber Lipogranulomatosis via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 spinal muscular atrophy with progressive myoclonic epilepsy 25.7 ACER3 ASAH1 CERS1 CLCA4 NAGA PSAP
2 lipogranulomatosis 10.4
3 arthritis 10.0
4 obstructive jaundice 10.0
5 spinal muscular atrophy 9.9
6 muscular atrophy 9.9
7 metachromatic leukodystrophy 9.8
8 leukodystrophy 9.8
9 mental retardation, x-linked 101 9.8 NAGA PSAP
10 bone angioendothelial sarcoma 9.5 NAGA PSAP

Graphical network of the top 20 diseases related to Farber Lipogranulomatosis:



Diseases related to Farber Lipogranulomatosis

Symptoms & Phenotypes for Farber Lipogranulomatosis

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Abdomen- Spleen:
splenomegaly

Skeletal:
arthritis
painful swollen joints

Respiratory- Larynx:
laryngeal nodules

Voice:
hoarse cry due to laryngeal involvement

Abdomen- Liver:
hepatomegaly

Neurologic- Central Nervous System:
irritability
motor retardation
mental retardation (in some patients)

Head And Neck- Eyes:
macular cherry-red spots (in some patients)

Skin Nails & Hair- Skin:
lipogranulomatosis
periarticular subcutaneous nodules
nodule show lipid-laden macrophages

Laboratory- Abnormalities:
elevated urine ceramide levels
histiocytic infiltration of liver, spleen, and lungs
ceramidase deficiency


Clinical features from OMIM:

228000

Human phenotypes related to Farber Lipogranulomatosis:

56 32 (show all 28)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 hallmark (90%) Very frequent (99-80%) HP:0004322
2 failure to thrive 56 32 hallmark (90%) Very frequent (99-80%) HP:0001508
3 nystagmus 56 32 frequent (33%) Frequent (79-30%) HP:0000639
4 recurrent respiratory infections 56 32 frequent (33%) Frequent (79-30%) HP:0002205
5 hepatomegaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0002240
6 splenomegaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0001744
7 kyphosis 56 32 frequent (33%) Frequent (79-30%) HP:0002808
8 osteoporosis 56 32 frequent (33%) Frequent (79-30%) HP:0000939
9 global developmental delay 56 32 occasional (7.5%) Occasional (29-5%) HP:0001263
10 intellectual disability 56 32 occasional (7.5%) Occasional (29-5%) HP:0001249
11 hoarse cry 56 32 frequent (33%) Frequent (79-30%) HP:0001615
12 joint stiffness 56 32 hallmark (90%) Very frequent (99-80%) HP:0001387
13 respiratory insufficiency 56 32 frequent (33%) Frequent (79-30%) HP:0002093
14 arthralgia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002829
15 pulmonary fibrosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0002206
16 decreased muscle mass 56 32 frequent (33%) Frequent (79-30%) HP:0003199
17 joint swelling 56 32 hallmark (90%) Very frequent (99-80%) HP:0001386
18 corneal opacity 56 32 occasional (7.5%) Occasional (29-5%) HP:0007957
19 laryngomalacia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001601
20 periarticular subcutaneous nodules 56 32 hallmark (90%) Very frequent (99-80%) HP:0007470
21 abnormality of vision 56 32 occasional (7.5%) Occasional (29-5%) HP:0000504
22 cherry red spot of the macula 56 32 occasional (7.5%) Occasional (29-5%) HP:0010729
23 irritability 32 HP:0000737
24 motor delay 32 HP:0001270
25 arthritis 32 HP:0001369
26 lipogranulomatosis 32 HP:0040139
27 abnormality of the eye 56 Occasional (29-5%)
28 subcutaneous nodule 56 Frequent (79-30%)

UMLS symptoms related to Farber Lipogranulomatosis:


painful swollen joints

Drugs & Therapeutics for Farber Lipogranulomatosis

Drugs for Farber Lipogranulomatosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lenalidomide Approved Phase 2 191732-72-6 216326
2 Angiogenesis Inhibitors Phase 2
3 Angiogenesis Modulating Agents Phase 2
4 Anti-Bacterial Agents Phase 2
5 Anti-Infective Agents Phase 2
6 Immunosuppressive Agents Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 A Study of Lenalidomide for Adult Histiocyte Disorders Recruiting NCT02523040 Phase 2 Lenalidomide
2 Farber Disease Natural History Study Recruiting NCT03233841
3 Biomarker for Farber Disease Recruiting NCT02298634

Search NIH Clinical Center for Farber Lipogranulomatosis

Cochrane evidence based reviews: farber lipogranulomatosis

Genetic Tests for Farber Lipogranulomatosis

Genetic tests related to Farber Lipogranulomatosis:

id Genetic test Affiliating Genes
1 Farber's Lipogranulomatosis 29
2 Farber Lipogranulomatosis 24 ASAH1

Anatomical Context for Farber Lipogranulomatosis

MalaCards organs/tissues related to Farber Lipogranulomatosis:

39
Liver, Skin, Spleen, Lung, Heart, Kidney, Lymph Node

Publications for Farber Lipogranulomatosis

Articles related to Farber Lipogranulomatosis:

id Title Authors Year
1
Farber lipogranulomatosis with predominant joint involvement mimicking juvenile idiopathic arthritis. ( 23385296 )
2013
2
Molecular analyses of novel ASAH1 mutations causing Farber lipogranulomatosis: analyses of exonic splicing enhancer inactivating mutation. ( 24355074 )
2013
3
Farber lipogranulomatosis type 1--late presentation and early death in a Croatian boy with a novel homozygous ASAH1 mutation. ( 20609603 )
2011
4
Farber lipogranulomatosis: clinical and molecular genetic analysis reveals a novel mutation in an Indian family. ( 16951918 )
2006
5
[Farber disease [Farber lipogranulomatosis], acid ceramidase deficiency]. ( 9645089 )
1998
6
A case of Farber lipogranulomatosis. ( 9539328 )
1998
7
Bone marrow involvement and obstructive jaundice in Farber lipogranulomatosis: clinical and autopsy report of a new case. ( 8892023 )
1996
8
Farber lipogranulomatosis: an unusual presentation in a black child. ( 2854742 )
1986

Variations for Farber Lipogranulomatosis

UniProtKB/Swiss-Prot genetic disease variations for Farber Lipogranulomatosis:

71 (show all 13)
id Symbol AA change Variation ID SNP ID
1 ASAH1 p.Thr222Lys VAR_008862 rs137853593
2 ASAH1 p.Tyr36Cys VAR_021579 rs137853595
3 ASAH1 p.Val97Glu VAR_021581
4 ASAH1 p.Glu138Val VAR_021582 rs137853594
5 ASAH1 p.Gly235Arg VAR_021583
6 ASAH1 p.Arg254Gly VAR_021584
7 ASAH1 p.Asn320Asp VAR_021585 rs137853596
8 ASAH1 p.Pro362Arg VAR_021586
9 ASAH1 p.Gln22His VAR_038166
10 ASAH1 p.His23Asp VAR_038167
11 ASAH1 p.Leu182Val VAR_038169 rs137853597
12 ASAH1 p.Val97Gly VAR_071994
13 ASAH1 p.Gly168Trp VAR_071995

ClinVar genetic disease variations for Farber Lipogranulomatosis:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 ASAH1 NM_004315.5(ASAH1): c.713C> A (p.Thr238Lys) single nucleotide variant Pathogenic rs137853593 GRCh37 Chromosome 8, 17919233: 17919233
2 ASAH1 NM_004315.5(ASAH1): c.461A> T (p.Glu154Val) single nucleotide variant Pathogenic rs137853594 GRCh37 Chromosome 8, 17922010: 17922010
3 ASAH1 NM_004315.5(ASAH1): c.155A> G (p.Tyr52Cys) single nucleotide variant Pathogenic rs137853595 GRCh37 Chromosome 8, 17933068: 17933068
4 ASAH1 NM_004315.5(ASAH1): c.1006A> G (p.Asn336Asp) single nucleotide variant Pathogenic rs137853596 GRCh37 Chromosome 8, 17916933: 17916933
5 ASAH1 NM_004315.5(ASAH1): c.592C> G (p.Leu198Val) single nucleotide variant Pathogenic rs137853597 GRCh37 Chromosome 8, 17919892: 17919892
6 ASAH1 NM_004315.5(ASAH1): c.965+4A> G single nucleotide variant Pathogenic rs397509415 GRCh37 Chromosome 8, 17917077: 17917077
7 ASAH1 NG_008985.1: g.14667_24138del9472 deletion Pathogenic GRCh37 Chromosome 8, 17923370: 17932841

Expression for Farber Lipogranulomatosis

Search GEO for disease gene expression data for Farber Lipogranulomatosis.

Pathways for Farber Lipogranulomatosis

Pathways related to Farber Lipogranulomatosis according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
11.33 ACER3 ASAH1 CERS1 PSAP
2 11.23 ASAH1 CERS1
3 11.22 ASAH1 NAGA PSAP

GO Terms for Farber Lipogranulomatosis

Cellular components related to Farber Lipogranulomatosis according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 lysosomal lumen GO:0043202 8.96 ASAH1 PSAP
2 lysosome GO:0005764 8.8 ASAH1 NAGA PSAP

Biological processes related to Farber Lipogranulomatosis according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.43 ASAH1 CERS1 PSAP
2 sphingolipid biosynthetic process GO:0030148 9.16 ACER3 CERS1
3 glycosphingolipid metabolic process GO:0006687 8.96 ASAH1 PSAP
4 ceramide metabolic process GO:0006672 8.62 ACER3 ASAH1

Molecular functions related to Farber Lipogranulomatosis according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 8.92 ACER3 ASAH1 CLCA4 NAGA

Sources for Farber Lipogranulomatosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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