MCID: DSM002
MIFTS: 36

Desmosterolosis

Categories: Genetic diseases, Rare diseases, Bone diseases, Metabolic diseases, Fetal diseases

Aliases & Classifications for Desmosterolosis

MalaCards integrated aliases for Desmosterolosis:

Name: Desmosterolosis 57 53 25 59 75 37 29 13 55 6 40 73
Deficiency of 3beta-Hydroxysterol Delta24-Reductase 25
Desmos 75

Characteristics:

Orphanet epidemiological data:

59
desmosterolosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Infancy,Neonatal; Age of death: any age,stillbirth;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
patients from 4 unrelated families have been reported (as of october 2011)
dysmorphic facial features may not be present


HPO:

32
desmosterolosis:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Desmosterolosis

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 35107Disease definitionDesmosterolosis is a very rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, and intellectual disability, with elevated levels of desmosterol.EpidemiologyOnly 9 cases have been reported in the literature to date.Clinical descriptionDesmosterolosis presents at birth with growth restriction, spasticity with variable degrees of hand contractures, either microcephaly or relative macrocephaly, and microretrognathia. Transient neonatal seizures, nystagmus, strabismus and failure to thrive are also seen in most cases. Intellectual disability occurs in all patients and is first noted by delayed milestones for speech and adaptive, fine and gross motor development. Less common manifestations reported include hirsutism, facial dysmorphism (downslanting palpebral fissures, bilateral epicanthal folds, submucous cleft palate, and thick alveolar ridges), sensorineural hearing loss, patent arterial duct, ambiguous genitalia, bilateral clubfeet, muscle wasting, and cutis aplasia. Optic atrophy, corpus callosum agenesis and loss of white matter are also noted.EtiologyDesmosterolosis is due to mutations in the DHCR24 gene (1p32.3) encoding 3-beta-hydroxysterol delta-24-reductase. This enzyme catalyzes the conversion of desmosterol (the cholesterol precursor) to cholesterol, which is highly involved in embryonic development and morphogenesis. Reduced enzyme activity leads to the accumulation of desmosterol and a lack of cholesterol, disrupting antenatal and postnatal development.Genetic counselingDesmosterolosis is inherited in an autosomal recessive manner and genetic counseling is possible.Visit the Orphanet disease page for more resources.

MalaCards based summary : Desmosterolosis, also known as deficiency of 3beta-hydroxysterol delta24-reductase, is related to greenberg dysplasia and smith-lemli-opitz syndrome, and has symptoms including muscle spasticity and seizures. An important gene associated with Desmosterolosis is DHCR24 (24-Dehydrocholesterol Reductase), and among its related pathways/superpathways are Steroid biosynthesis and Metabolic pathways. The drug Phytosterol has been mentioned in the context of this disorder. Affiliated tissues include brain, bone and skin, and related phenotypes are macrocephaly and low-set ears

Genetics Home Reference : 25 Desmosterolosis is a condition that is characterized by neurological problems, such as brain abnormalities and developmental delay, and can also include other signs and symptoms.

OMIM : 57 Desmosterolosis is a rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells (summary by Waterham et al., 2001). (602398)

UniProtKB/Swiss-Prot : 75 Desmosterolosis: Rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.

Wikipedia : 76 Desmosterolosis is a defect in cholesterol biosynthesis. It results in an accumulation of... more...

Related Diseases for Desmosterolosis

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

# Related Disease Score Top Affiliating Genes
1 greenberg dysplasia 10.9
2 smith-lemli-opitz syndrome 10.9
3 osteoblastoma 10.1
4 aneurysmal bone cysts 9.9
5 aneurysm 9.9
6 corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia 9.9
7 microcephaly 9.9
8 retinitis 9.9
9 spasticity 9.9

Graphical network of the top 20 diseases related to Desmosterolosis:



Diseases related to Desmosterolosis

Symptoms & Phenotypes for Desmosterolosis

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears
posteriorly rotated ears

Neurologic Central Nervous System:
hydrocephalus
seizures
spasticity
ventriculomegaly
delayed psychomotor development, severe
more
Growth Other:
failure to thrive

Head And Neck Head:
microcephaly
macrocephaly, relative

Genitourinary External Genitalia Male:
ambiguous genitalia

Skeletal Limbs:
rhizomelic shortening

Skeletal Hands:
contractures of the hands

Laboratory Abnormalities:
elevated plasma desmosterol

Head And Neck Face:
frontal bossing
micrognathia

Head And Neck Eyes:
nystagmus
strabismus

Head And Neck Nose:
short nose
anteverted nares
hypoplastic nasal bridge

Head And Neck Mouth:
cleft palate
thick alveolar ridges
gingival nodules

Genitourinary External Genitalia Female:
ambiguous genitalia

Skeletal:
osteosclerosis
arthrogryposis

Cardiovascular Heart:
total anomalous pulmonary venous drainage (1 patient)


Clinical features from OMIM:

602398

Human phenotypes related to Desmosterolosis:

59 32 (show top 50) (show all 76)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 very rare (1%) Occasional (29-5%) HP:0000256
2 low-set ears 59 32 very rare (1%) Frequent (79-30%) HP:0000369
3 agenesis of corpus callosum 59 32 hallmark (90%) Very frequent (99-80%) HP:0001274
4 frontal bossing 59 32 very rare (1%) Occasional (29-5%) HP:0002007
5 hydrocephalus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000238
6 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
7 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
8 seizures 59 32 Frequent (79-30%) HP:0001250
9 spasticity 59 32 hallmark (90%) Very frequent (99-80%) HP:0001257
10 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
11 splenomegaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001744
12 depressed nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0005280
13 short nose 59 32 frequent (33%) Frequent (79-30%) HP:0003196
14 microcephaly 59 32 very rare (1%) Very frequent (99-80%) HP:0000252
15 prominent forehead 59 32 occasional (7.5%) Occasional (29-5%) HP:0011220
16 cleft palate 59 32 very rare (1%) Very frequent (99-80%) HP:0000175
17 micrognathia 59 32 very rare (1%) Very frequent (99-80%) HP:0000347
18 feeding difficulties 59 32 hallmark (90%) Very frequent (99-80%) HP:0011968
19 retrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000278
20 strabismus 59 32 frequent (33%) Frequent (79-30%) HP:0000486
21 patent ductus arteriosus 59 32 very rare (1%) Occasional (29-5%) HP:0001643
22 micromelia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002983
23 epicanthus 59 32 very rare (1%) Occasional (29-5%) HP:0000286
24 metatarsus adductus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001840
25 intrauterine growth retardation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001511
26 ventriculomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0002119
27 rigidity 59 32 hallmark (90%) Very frequent (99-80%) HP:0002063
28 low-set, posteriorly rotated ears 59 32 frequent (33%) Frequent (79-30%) HP:0000368
29 downslanted palpebral fissures 59 32 very rare (1%) Occasional (29-5%) HP:0000494
30 narrow mouth 59 32 frequent (33%) Frequent (79-30%) HP:0000160
31 intestinal malrotation 59 32 occasional (7.5%) Occasional (29-5%) HP:0002566
32 severe short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0003510
33 absent septum pellucidum 59 32 hallmark (90%) Very frequent (99-80%) HP:0001331
34 ambiguous genitalia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000062
35 large earlobe 59 32 frequent (33%) Frequent (79-30%) HP:0009748
36 pachygyria 59 32 occasional (7.5%) Occasional (29-5%) HP:0001302
37 polymicrogyria 59 32 occasional (7.5%) Occasional (29-5%) HP:0002126
38 talipes 59 32 occasional (7.5%) Occasional (29-5%) HP:0001883
39 bifid uvula 59 32 hallmark (90%) Very frequent (99-80%) HP:0000193
40 status epilepticus 59 32 frequent (33%) Frequent (79-30%) HP:0002133
41 submucous cleft hard palate 59 32 hallmark (90%) Very frequent (99-80%) HP:0000176
42 renal agenesis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000104
43 osteopetrosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0011002
44 anomalous pulmonary venous return 59 32 occasional (7.5%) Occasional (29-5%) HP:0010772
45 dermal atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0004334
46 muscle stiffness 59 32 hallmark (90%) Very frequent (99-80%) HP:0003552
47 macrogyria 59 32 occasional (7.5%) Occasional (29-5%) HP:0007227
48 global developmental delay 32 very rare (1%) HP:0001263
49 anteverted nares 32 HP:0000463
50 hypertonia 59 Very frequent (99-80%)

UMLS symptoms related to Desmosterolosis:


muscle spasticity, seizures

Drugs & Therapeutics for Desmosterolosis

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Phytosterol Nutraceutical

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Inborn Errors of Cholesterol Synthesis and Related Disorders Recruiting NCT00046202

Search NIH Clinical Center for Desmosterolosis

Genetic Tests for Desmosterolosis

Genetic tests related to Desmosterolosis:

# Genetic test Affiliating Genes
1 Desmosterolosis 29 DHCR24

Anatomical Context for Desmosterolosis

MalaCards organs/tissues related to Desmosterolosis:

41
Brain, Bone, Skin

Publications for Desmosterolosis

Articles related to Desmosterolosis:

# Title Authors Year
1
Desmosterolosis presenting with multiple congenital anomalies. ( 29175559 )
2018
2
Desmosterolosis: an illustration of diagnostic ambiguity of cholesterol synthesis disorders. ( 24961299 )
2014
3
The desmosterolosis phenotype: spasticity, microcephaly and micrognathia with agenesis of corpus callosum and loss of white matter. ( 21559050 )
2011
4
Desmosterolosis-phenotypic and molecular characterization of a third case and review of the literature. ( 21671375 )
2011
5
Differential effects of cholesterol and desmosterol on the ligand binding function of the hippocampal serotonin(1A) receptor: implications in desmosterolosis. ( 19616511 )
2009
6
Desmosterolosis presenting with multiple congenital anomalies and profound developmental delay. ( 12457401 )
2002
7
Mutations in the 3beta-hydroxysterol delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis. ( 11519011 )
2001
8
Retinal structure and function in an animal model that replicates the biochemical hallmarks of desmosterolosis. ( 10905631 )
2000
9
Clinical phenotype of desmosterolosis. ( 9450875 )
1998
10
Desmosterolosis: a new inborn error of cholesterol biosynthesis. ( 8709748 )
1996

Variations for Desmosterolosis

UniProtKB/Swiss-Prot genetic disease variations for Desmosterolosis:

75
# Symbol AA change Variation ID SNP ID
1 DHCR24 p.Glu191Lys VAR_012732 rs119475041
2 DHCR24 p.Asn294Thr VAR_012733 rs281797257
3 DHCR24 p.Lys306Asn VAR_012734 rs281797256
4 DHCR24 p.Tyr471Ser VAR_012735 rs28939092

ClinVar genetic disease variations for Desmosterolosis:

6
(show top 50) (show all 128)
# Gene Variation Type Significance SNP ID Assembly Location
1 DHCR24 NM_014762.3(DHCR24): c.1412A> C (p.Tyr471Ser) single nucleotide variant Pathogenic rs28939092 GRCh37 Chromosome 1, 55318045: 55318045
2 DHCR24 NM_014762.3(DHCR24): c.1412A> C (p.Tyr471Ser) single nucleotide variant Pathogenic rs28939092 GRCh38 Chromosome 1, 54852372: 54852372
3 DHCR24 NM_014762.3(DHCR24): c.571G> A (p.Glu191Lys) single nucleotide variant Likely pathogenic rs119475041 GRCh37 Chromosome 1, 55340807: 55340807
4 DHCR24 NM_014762.3(DHCR24): c.571G> A (p.Glu191Lys) single nucleotide variant Likely pathogenic rs119475041 GRCh38 Chromosome 1, 54875134: 54875134
5 DHCR24 NM_014762.3(DHCR24): c.307C> T (p.Arg103Cys) single nucleotide variant Pathogenic rs387906938 GRCh37 Chromosome 1, 55349371: 55349371
6 DHCR24 NM_014762.3(DHCR24): c.307C> T (p.Arg103Cys) single nucleotide variant Pathogenic rs387906938 GRCh38 Chromosome 1, 54883698: 54883698
7 DHCR24 NM_014762.3(DHCR24): c.281G> A (p.Arg94His) single nucleotide variant Pathogenic rs387906939 GRCh37 Chromosome 1, 55349397: 55349397
8 DHCR24 NM_014762.3(DHCR24): c.281G> A (p.Arg94His) single nucleotide variant Pathogenic rs387906939 GRCh38 Chromosome 1, 54883724: 54883724
9 DHCR24 NM_014762.3(DHCR24): c.1438G> A (p.Glu480Lys) single nucleotide variant Pathogenic rs387906940 GRCh37 Chromosome 1, 55318019: 55318019
10 DHCR24 NM_014762.3(DHCR24): c.1438G> A (p.Glu480Lys) single nucleotide variant Pathogenic rs387906940 GRCh38 Chromosome 1, 54852346: 54852346
11 DHCR24 NM_014762.3(DHCR24): c.81C> T (p.Leu27=) single nucleotide variant Conflicting interpretations of pathogenicity rs140995590 GRCh37 Chromosome 1, 55352712: 55352712
12 DHCR24 NM_014762.3(DHCR24): c.81C> T (p.Leu27=) single nucleotide variant Conflicting interpretations of pathogenicity rs140995590 GRCh38 Chromosome 1, 54887039: 54887039
13 DHCR24 NM_014762.3(DHCR24): c.*2503C> T single nucleotide variant Uncertain significance rs886046412 GRCh38 Chromosome 1, 54849730: 54849730
14 DHCR24 NM_014762.3(DHCR24): c.*2503C> T single nucleotide variant Uncertain significance rs886046412 GRCh37 Chromosome 1, 55315403: 55315403
15 DHCR24 NM_014762.3(DHCR24): c.*2119C> T single nucleotide variant Uncertain significance rs886046414 GRCh38 Chromosome 1, 54850114: 54850114
16 DHCR24 NM_014762.3(DHCR24): c.*2119C> T single nucleotide variant Uncertain significance rs886046414 GRCh37 Chromosome 1, 55315787: 55315787
17 DHCR24 NM_014762.3(DHCR24): c.*1264T> C single nucleotide variant Uncertain significance rs553462271 GRCh38 Chromosome 1, 54850969: 54850969
18 DHCR24 NM_014762.3(DHCR24): c.*1264T> C single nucleotide variant Uncertain significance rs553462271 GRCh37 Chromosome 1, 55316642: 55316642
19 DHCR24 NM_014762.3(DHCR24): c.*944C> T single nucleotide variant Uncertain significance rs79299252 GRCh38 Chromosome 1, 54851289: 54851289
20 DHCR24 NM_014762.3(DHCR24): c.*944C> T single nucleotide variant Uncertain significance rs79299252 GRCh37 Chromosome 1, 55316962: 55316962
21 DHCR24 NM_014762.3(DHCR24): c.*914G> A single nucleotide variant Uncertain significance rs140759061 GRCh38 Chromosome 1, 54851319: 54851319
22 DHCR24 NM_014762.3(DHCR24): c.*914G> A single nucleotide variant Uncertain significance rs140759061 GRCh37 Chromosome 1, 55316992: 55316992
23 DHCR24 NM_014762.3(DHCR24): c.*731T> C single nucleotide variant Uncertain significance rs116289873 GRCh38 Chromosome 1, 54851502: 54851502
24 DHCR24 NM_014762.3(DHCR24): c.*731T> C single nucleotide variant Uncertain significance rs116289873 GRCh37 Chromosome 1, 55317175: 55317175
25 DHCR24 NM_014762.3(DHCR24): c.*718G> A single nucleotide variant Uncertain significance rs74072035 GRCh38 Chromosome 1, 54851515: 54851515
26 DHCR24 NM_014762.3(DHCR24): c.*718G> A single nucleotide variant Uncertain significance rs74072035 GRCh37 Chromosome 1, 55317188: 55317188
27 DHCR24 NM_014762.3(DHCR24): c.*508T> C single nucleotide variant Uncertain significance rs886046416 GRCh37 Chromosome 1, 55317398: 55317398
28 DHCR24 NM_014762.3(DHCR24): c.*508T> C single nucleotide variant Uncertain significance rs886046416 GRCh38 Chromosome 1, 54851725: 54851725
29 DHCR24 NM_014762.3(DHCR24): c.*480C> T single nucleotide variant Uncertain significance rs576670614 GRCh38 Chromosome 1, 54851753: 54851753
30 DHCR24 NM_014762.3(DHCR24): c.*480C> T single nucleotide variant Uncertain significance rs576670614 GRCh37 Chromosome 1, 55317426: 55317426
31 DHCR24 NM_014762.3(DHCR24): c.*393G> A single nucleotide variant Uncertain significance rs146650872 GRCh38 Chromosome 1, 54851840: 54851840
32 DHCR24 NM_014762.3(DHCR24): c.*393G> A single nucleotide variant Uncertain significance rs146650872 GRCh37 Chromosome 1, 55317513: 55317513
33 DHCR24 NM_014762.3(DHCR24): c.*392C> T single nucleotide variant Uncertain significance rs116490123 GRCh37 Chromosome 1, 55317514: 55317514
34 DHCR24 NM_014762.3(DHCR24): c.*392C> T single nucleotide variant Uncertain significance rs116490123 GRCh38 Chromosome 1, 54851841: 54851841
35 DHCR24 NM_014762.3(DHCR24): c.*316T> G single nucleotide variant Uncertain significance rs74072037 GRCh38 Chromosome 1, 54851917: 54851917
36 DHCR24 NM_014762.3(DHCR24): c.*316T> G single nucleotide variant Uncertain significance rs74072037 GRCh37 Chromosome 1, 55317590: 55317590
37 DHCR24 NM_014762.3(DHCR24): c.726C> A (p.Phe242Leu) single nucleotide variant Uncertain significance rs138043637 GRCh38 Chromosome 1, 54871500: 54871500
38 DHCR24 NM_014762.3(DHCR24): c.726C> A (p.Phe242Leu) single nucleotide variant Uncertain significance rs138043637 GRCh37 Chromosome 1, 55337173: 55337173
39 DHCR24 NM_014762.3(DHCR24): c.639C> T (p.Ala213=) single nucleotide variant Uncertain significance rs143779194 GRCh38 Chromosome 1, 54871587: 54871587
40 DHCR24 NM_014762.3(DHCR24): c.639C> T (p.Ala213=) single nucleotide variant Uncertain significance rs143779194 GRCh37 Chromosome 1, 55337260: 55337260
41 DHCR24 NM_014762.3(DHCR24): c.*2555A> G single nucleotide variant Benign rs657688 GRCh38 Chromosome 1, 54849678: 54849678
42 DHCR24 NM_014762.3(DHCR24): c.*2555A> G single nucleotide variant Benign rs657688 GRCh37 Chromosome 1, 55315351: 55315351
43 DHCR24 NM_014762.3(DHCR24): c.*2514A> G single nucleotide variant Uncertain significance rs532882730 GRCh38 Chromosome 1, 54849719: 54849719
44 DHCR24 NM_014762.3(DHCR24): c.*2514A> G single nucleotide variant Uncertain significance rs532882730 GRCh37 Chromosome 1, 55315392: 55315392
45 DHCR24 NM_014762.3(DHCR24): c.*2442G> T single nucleotide variant Uncertain significance rs115017311 GRCh38 Chromosome 1, 54849791: 54849791
46 DHCR24 NM_014762.3(DHCR24): c.*2442G> T single nucleotide variant Uncertain significance rs115017311 GRCh37 Chromosome 1, 55315464: 55315464
47 DHCR24 NM_014762.3(DHCR24): c.*1881G> A single nucleotide variant Uncertain significance rs757634950 GRCh38 Chromosome 1, 54850352: 54850352
48 DHCR24 NM_014762.3(DHCR24): c.*1881G> A single nucleotide variant Uncertain significance rs757634950 GRCh37 Chromosome 1, 55316025: 55316025
49 DHCR24 NM_014762.3(DHCR24): c.*1489G> A single nucleotide variant Uncertain significance rs192013345 GRCh38 Chromosome 1, 54850744: 54850744
50 DHCR24 NM_014762.3(DHCR24): c.*1489G> A single nucleotide variant Uncertain significance rs192013345 GRCh37 Chromosome 1, 55316417: 55316417

Expression for Desmosterolosis

Search GEO for disease gene expression data for Desmosterolosis.

Pathways for Desmosterolosis

Pathways related to Desmosterolosis according to KEGG:

37
# Name Kegg Source Accession
1 Steroid biosynthesis hsa00100
2 Metabolic pathways hsa01100

GO Terms for Desmosterolosis

Sources for Desmosterolosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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