Farber lipogranulomatosis

General Information (adopted from Orphanet):

Synonyms, Signs: AC deficiency
Farber disease
Ceramidase deficiency
N-Laurylsphingosine deacylase deficiency
Acid ceramidase deficiency
Number of Symptoms 39
OrphanetNr: 333
OMIM Id: 228000
ICD-10: E75.2
UMLs: C0268255
C2936785
MeSH: C537075
D055577
MedDRA:
Snomed: 79935000

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Genetic subcutaneous tissue disease
 -Rare genetic disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease
Sphingolipidosis
 -Rare genetic disease
Sphingolipidosis with epilepsy
 -Rare neurologic disease
Subcutaneous tissue disease
 -Rare skin disease
Unclassified primitive or secondary maculopathy
 -Rare eye disease
 -Rare genetic disease

Comment:

Farber disease (FD) is a rare autosomal recessive disease caused by mutations in the acid ceramidase gene (ASAH1). Low ceramidase activity results in the accumulation of fatty substances, mainly ceramides. Hallmark symptoms at clinical level are periarticular nodules, lipogranulomas, swollen and painful joints and a hoarse voice. FD phenotypes are heterogeneous varying from mild to very severe cases, with the patients not surviving past their first year of life. The diagnostic aspects of FD are poorly developed due to the rarity of the disease (PMID:28733637).

Symptom Information: Sort by abundance 

1
 (HPO:0008002) Abnormality of macular pigmentation Occasional [Orphanet] 3103372 IBIS 20 / 7739
2
 (HPO:0010729) Cherry red spot of the macula 3103372 IBIS 10 / 7739
3
 (HPO:0000639) Nystagmus Frequent [Orphanet] 9539328 IBIS 555 / 7739
4
 (HPO:0006515) Interstitial pneumonitis 17603888 IBIS 13 / 7739
5
 (HPO:0002093) Respiratory insufficiency Frequent [Orphanet] 29152458 IBIS 410 / 7739
6
 (HPO:0002205) Recurrent respiratory infections Frequent [Orphanet] 29152458 IBIS 254 / 7739
7
 (HPO:0001608) Abnormality of the voice Frequent [Orphanet] 29152458 IBIS 126 / 7739
8
 (HPO:0001615) Hoarse cry 29152458 IBIS 5 / 7739
9
 (HPO:0001031) Subcutaneous lipoma Frequent [Orphanet] 8747852 IBIS 112 / 7739
10
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 29152458 IBIS 492 / 7739
11
 (HPO:0001508) Failure to thrive 29152458 IBIS 454 / 7739
12
 (HPO:0001386) Joint swelling 29152458 IBIS 7 / 7739
13
 (HPO:0003202) Skeletal muscle atrophy Frequent [Orphanet] 29152458 IBIS 281 / 7739
14
 (HPO:0001270) Motor delay 29152458 IBIS 322 / 7739
15
 (HPO:0002123) Generalized myoclonic seizures 29152458 IBIS 62 / 7739
16
 (HPO:0000939) Osteoporosis 9539328 IBIS 129 / 7739
17
 (HPO:0005059) Arthralgia/arthritis Very frequent [Orphanet] 29152458 IBIS 141 / 7739
18
 (HPO:0001369) Arthritis 29152458 IBIS 44 / 7739
19
 (HPO:0001387) Joint stiffness Very frequent [Orphanet] 17603888 IBIS 322 / 7739
20
 (HPO:0001367) Abnormal joint morphology Occasional [Orphanet] 29152458 IBIS 53 / 7739
21
 (HPO:0002240) Hepatomegaly Very frequent [Orphanet] 29152458 IBIS 467 / 7739
22
 (HPO:0001433) Hepatosplenomegaly 8747852 IBIS 78 / 7739
23
 (HPO:0001744) Splenomegaly Occasional [Orphanet] 17603888 IBIS 337 / 7739
24
 (HPO:0000478) Abnormality of the eye Occasional [Orphanet] 3103372 IBIS 126 / 7739
25
 (HPO:0007470) Periarticular subcutaneous nodules 29152458 IBIS 1 / 7739
26
 (HPO:0000007) Autosomal recessive inheritance 29152458 IBIS 2538 / 7739
27
 (HPO:0011421) Death in adolescence 17603888 IBIS 1 / 7739
28
 (HPO:0001522) Death in infancy 17603888 IBIS 275 / 7739
29
 (HPO:0040139) Lipogranulomatosis 29152458 IBIS 1 / 7739
30
 (HPO:0012758) Neurodevelopmental delay Occasional [Orphanet] 9539328 IBIS 949 / 7739
31
 (HPO:0003676) Progressive disorder 29152458 IBIS 148 / 7739
32
 (HPO:0003828) Variable expressivity 29152458 IBIS 130 / 7739
33
 (OMIM) Ceramidase deficiency 29152458 IBIS 1 / 7739
34
 (OMIM) Elevated urine ceramide levels 29152458 IBIS 1 / 7739
35
 (OMIM) Histiocytic infiltration of liver, spleen, and lungs 29152458 IBIS 1 / 7739
36
 (OMIM) Hoarse cry due to laryngeal involvement 29152458 IBIS 1 / 7739
37
 (OMIM) Laryngeal nodules 29152458 IBIS 1 / 7739
38
 (OMIM) Nodule show lipid-laden macrophages 29152458 IBIS 1 / 7739
39
 (OMIM) Painful swollen joints 29152458 IBIS 1 / 7739

Associated genes:

ASAH1

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Diagnosis OMIM Ben-Yoseph et al. (1989) used N-laurylsphingosine deacylase as a substrate for studying the usefulness of plasma specimens for diagnosis and carrier detection of Farber disease. This made a highly sensitive assay because the substrate is cleaved by acid ceramidase ...
Clinical Description OMIM In the few reported cases of Farber disease, manifestations appeared in the first few weeks of life and consisted of irritability, hoarse cry, and nodular, erythematous swellings of the wrists and other sites, particularly those subject to trauma. Severe ...
Molecular genetics OMIM In a patient with Farber disease, Koch et al. (1996) identified a homoallelic thr222-to-lys (T222K; 613468.0001) in the ASAH1 gene.

Bar et al. (2001) identified 6 novel mutations in the ASAH gene causing Farber disease: 3 point ...