MCID: LTH002
MIFTS: 34

Lathosterolosis

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Lathosterolosis

MalaCards integrated aliases for Lathosterolosis:

Name: Lathosterolosis 57 53 59 75 37 29 13 55 6 40 73
Sterol C5-Desaturase Deficiency 57 53 59
Sc5d Deficiency 57 53
Lathst 75

Characteristics:

Orphanet epidemiological data:

59
lathosterolosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
lathosterolosis:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


Summaries for Lathosterolosis

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 46059Disease definitionLathosterolosis is an extremely rare inborn error of sterol biosynthesis characterized by facial dysmorphism, congenital anomalies (including limb and kidney anomalies), failure to thrive, developmental delay and liver disease.EpidemiologyOnly 4 cases have been reported in the literature to date.Clinical descriptionMicrocephaly is present at birth along with hypotonia, failure to thrive and facial dysmorphic features such as bitemporal narrowing, ptosis, puffy cheeks, and micrognathia. Limb anomalies that have been reported include postaxial polydactyly of upper or lower limbs (mainly feet), bilateral syndactyly between the 2nd and 3rd or 2nd and 4th toes and bilateral club feet. Developmental delay and learning disability starting in early childhood have been noted in all patients. Additional anomalies have also been reported such as corneal clouding, cataract, conductive hearing loss, gingival hypertrophy, ambiguous genitalia, horseshoe kidney (see this term) and neurological manifestations (i.e. myoclonus). Liver disease seen in patients ranges from hypertransaminasemia to progressive cholestasis and can lead to end stage hepatic disease, occurring in childhood.EtiologyLathosterolosis is due to mutations in the SC5D gene (11q23.3). A mutation in this gene leads to a deficiency in 3-beta-hydroxysteroid-delta-5-desaturase, which is necessary in the conversion of lathosterol into 7-dehydrocholesterol. This prevents the synthesis of cholesterol, which among other functions acts as a structural lipid, a precursor for bile acids and steroid hormones, and is necessary for the maturation of hedgehog morphogens during embryonic development.Diagnostic methodsDiagnosis is based on clinical and biochemical findings. An elevation of lathosterol by gas chromatography/mass spectroscopy (GC/MS) is noted in both skin fibroblasts and plasma. The levels of 7-dehydrocholesterol and cholesterol are normal or low. Molecular genetic testing revealing mutations in the SC5D gene confirms the diagnosis.Differential diagnosisThe main differential diagnosis is Smith-Lemli-Opitz syndrome (see this term) that shares many clinical features with lathosterolosis but that can be excluded with biochemical and genetic testing.Antenatal diagnosisPrenatal diagnosis is feasible if the mutations are known but it has never been performed given the rarity of the disease.Genetic counselingLathosterolosis is inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes and they therefore have a 25% chance of having an affected child with each pregnancy.Management and treatmentTreatment involves cholesterol supplementation and reduction of 7-hydrocholesterol. Simvastin, a 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitor, has been proven to be beneficial in normalizing the lathosterol level in one patient. Liver transplantation was successful in normalizing liver function and cholesterol levels in a patient who had developed end stage liver disease. Moreover, it appeared to improve neurocognitive functions. Regular opthalmological evalutations and ultrasound monitoring of the liver are recommended.PrognosisThe prognosis is poor but treatment appears to prolong life and arrest progression of neurological damage.Visit the Orphanet disease page for more resources.

MalaCards based summary : Lathosterolosis, also known as sterol c5-desaturase deficiency, is related to smith-lemli-opitz syndrome and greenberg dysplasia. An important gene associated with Lathosterolosis is SC5D (Sterol-C5-Desaturase), and among its related pathways/superpathways is Steroid biosynthesis. The drug Phytosterol has been mentioned in the context of this disorder. Affiliated tissues include liver, kidney and skin, and related phenotypes are high palate and ptosis

UniProtKB/Swiss-Prot : 75 Lathosterolosis: Autosomal recessive disorder characterized by a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease.

Wikipedia : 76 Lathosterolosis is a defect in cholesterol... more...

Description from OMIM: 607330

Related Diseases for Lathosterolosis

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

# Related Disease Score Top Affiliating Genes
1 smith-lemli-opitz syndrome 11.3
2 greenberg dysplasia 10.9
3 opitz gbbb syndrome, type i 9.9
4 cataract 9.9

Symptoms & Phenotypes for Lathosterolosis

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
cataract
epicanthal folds

Head And Neck Nose:
anteverted nares
broad nasal bridge

Head And Neck Face:
long philtrum
micrognathia
sloping forehead
bitemporal narrowing

Abdomen Liver:
intrahepatic cholestasis

Hematology:
anisopoikilocytosis
large platelets
acanthocytes
schistocytes
vacuolated monocytes

Head And Neck Ears:
conductive hearing loss

Skeletal Hands:
postaxial hexadactyly

Abdomen Biliary Tract:
bilobate gallbladder

Head And Neck Head:
microcephaly

Skeletal:
osteoporosis
pathologic fracture

Laboratory Abnormalities:
hyperbilirubinemia
elevated alkaline phosphatase
elevated transaminases
elevated lathosterol
absent 7-dehydrocholesterol
more
Skeletal Feet:
syndactyly
clubfeet
postaxial hexadactyly

Neurologic Central Nervous System:
hypotonia
mental retardation
type ii arnold chiari malformation
lumbosacral meningocele

Head And Neck Mouth:
high-arched palate
thin lips
prominent upper lip

Genitourinary Kidneys:
pyelectasis

Skeletal Spine:
sagittal vertebral cleft


Clinical features from OMIM:

607330

Human phenotypes related to Lathosterolosis:

59 32 (show top 50) (show all 70)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 high palate 59 32 very rare (1%) Frequent (79-30%) HP:0000218
2 ptosis 59 32 very rare (1%) Frequent (79-30%) HP:0000508
3 seizures 59 32 very rare (1%) Frequent (79-30%) HP:0001250
4 muscular hypotonia 59 32 very rare (1%) Frequent (79-30%) HP:0001252
5 failure to thrive 59 32 frequent (33%) Frequent (79-30%) HP:0001508
6 cerebral calcification 59 32 frequent (33%) Frequent (79-30%) HP:0002514
7 gingival overgrowth 59 32 very rare (1%) Frequent (79-30%) HP:0000212
8 hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000365
9 cataract 59 32 very rare (1%) Very frequent (99-80%) HP:0000518
10 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
11 hepatomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0002240
12 short nose 59 32 very rare (1%) Frequent (79-30%) HP:0003196
13 microcephaly 59 32 very rare (1%) Very frequent (99-80%) HP:0000252
14 anteverted nares 59 32 very rare (1%) Frequent (79-30%) HP:0000463
15 full cheeks 59 32 frequent (33%) Frequent (79-30%) HP:0000293
16 long philtrum 59 32 very rare (1%) Frequent (79-30%) HP:0000343
17 micrognathia 59 32 very rare (1%) Frequent (79-30%) HP:0000347
18 opacification of the corneal stroma 59 32 very rare (1%) Frequent (79-30%) HP:0007759
19 epicanthus 59 32 very rare (1%) Frequent (79-30%) HP:0000286
20 myoclonus 59 32 frequent (33%) Frequent (79-30%) HP:0001336
21 biparietal narrowing 59 32 frequent (33%) Frequent (79-30%) HP:0004422
22 intrauterine growth retardation 59 32 frequent (33%) Frequent (79-30%) HP:0001511
23 specific learning disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001328
24 horseshoe kidney 59 32 very rare (1%) Frequent (79-30%) HP:0000085
25 thrombocytopenia 59 32 frequent (33%) Frequent (79-30%) HP:0001873
26 arnold-chiari malformation 59 32 very rare (1%) Frequent (79-30%) HP:0002308
27 downslanted palpebral fissures 59 32 very rare (1%) Frequent (79-30%) HP:0000494
28 meningocele 59 32 frequent (33%) Frequent (79-30%) HP:0002435
29 downturned corners of mouth 59 32 frequent (33%) Frequent (79-30%) HP:0002714
30 bulbous nose 59 32 frequent (33%) Frequent (79-30%) HP:0000414
31 hypoplasia of penis 59 32 hallmark (90%) Very frequent (99-80%) HP:0008736
32 abnormal platelet morphology 59 32 frequent (33%) Frequent (79-30%) HP:0011875
33 hepatic failure 59 32 frequent (33%) Frequent (79-30%) HP:0001399
34 toe syndactyly 59 32 very rare (1%) Frequent (79-30%) HP:0001770
35 microcornea 59 32 frequent (33%) Frequent (79-30%) HP:0000482
36 postaxial hand polydactyly 59 32 very rare (1%) Frequent (79-30%) HP:0001162
37 postaxial foot polydactyly 59 32 very rare (1%) Very frequent (99-80%) HP:0001830
38 sloping forehead 59 32 very rare (1%) Frequent (79-30%) HP:0000340
39 talipes 59 32 frequent (33%) Frequent (79-30%) HP:0001883
40 prominent metopic ridge 59 32 frequent (33%) Frequent (79-30%) HP:0005487
41 intrahepatic cholestasis 59 32 very rare (1%) Frequent (79-30%) HP:0001406
42 cerebellar cortical atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0008278
43 narrow forehead 59 32 very rare (1%) Frequent (79-30%) HP:0000341
44 anisopoikilocytosis 59 32 very rare (1%) Frequent (79-30%) HP:0004823
45 abnormality of the thoracic spine 59 32 frequent (33%) Frequent (79-30%) HP:0100711
46 intellectual disability 32 very rare (1%) HP:0001249
47 wide nasal bridge 32 very rare (1%) HP:0000431
48 osteoporosis 32 very rare (1%) HP:0000939
49 pathologic fracture 32 very rare (1%) HP:0002756
50 growth delay 32 very rare (1%) HP:0001510

Drugs & Therapeutics for Lathosterolosis

Drugs for Lathosterolosis (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 Lathosterolosis

Genetic Tests for Lathosterolosis

Genetic tests related to Lathosterolosis:

# Genetic test Affiliating Genes
1 Lathosterolosis 29 SC5D

Anatomical Context for Lathosterolosis

MalaCards organs/tissues related to Lathosterolosis:

41
Liver, Kidney, Skin, Testes, Monocytes

Publications for Lathosterolosis

Articles related to Lathosterolosis:

# Title Authors Year
1
Liver transplantation in defects of cholesterol biosynthesis: the case of lathosterolosis. ( 24621408 )
2014
2
Lathosterolosis: a disorder of cholesterol biosynthesis resembling smith-lemli-opitz syndrome. ( 24142275 )
2014
3
Cataract development in a young patient with lathosterolosis: a clinicopathologic case report. ( 19123163 )
2009
4
Clinical phenotype of lathosterolosis. ( 17853487 )
2007
5
Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency. ( 12812989 )
2003
6
Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5- desaturase. ( 12189593 )
2002

Variations for Lathosterolosis

UniProtKB/Swiss-Prot genetic disease variations for Lathosterolosis:

75
# Symbol AA change Variation ID SNP ID
1 SC5D p.Arg29Gln VAR_014423 rs104894295
2 SC5D p.Gly211Asp VAR_014424 rs104894296
3 SC5D p.Tyr46Ser VAR_020829 rs104894297

ClinVar genetic disease variations for Lathosterolosis:

6
(show top 50) (show all 160)
# Gene Variation Type Significance SNP ID Assembly Location
1 SC5D NM_006918.4(SC5D): c.86G> A (p.Arg29Gln) single nucleotide variant Pathogenic rs104894295 GRCh37 Chromosome 11, 121174170: 121174170
2 SC5D NM_006918.4(SC5D): c.86G> A (p.Arg29Gln) single nucleotide variant Pathogenic rs104894295 GRCh38 Chromosome 11, 121303461: 121303461
3 SC5D NM_006918.4(SC5D): c.632G> A (p.Gly211Asp) single nucleotide variant Pathogenic rs104894296 GRCh37 Chromosome 11, 121177953: 121177953
4 SC5D NM_006918.4(SC5D): c.632G> A (p.Gly211Asp) single nucleotide variant Pathogenic rs104894296 GRCh38 Chromosome 11, 121307244: 121307244
5 SC5D NM_006918.4(SC5D): c.137A> C (p.Tyr46Ser) single nucleotide variant Pathogenic rs104894297 GRCh37 Chromosome 11, 121174221: 121174221
6 SC5D NM_006918.4(SC5D): c.137A> C (p.Tyr46Ser) single nucleotide variant Pathogenic rs104894297 GRCh38 Chromosome 11, 121303512: 121303512
7 SC5D NM_006918.4(SC5D): c.-127T> G single nucleotide variant Uncertain significance rs886047847 GRCh37 Chromosome 11, 121163409: 121163409
8 SC5D NM_006918.4(SC5D): c.-127T> G single nucleotide variant Uncertain significance rs886047847 GRCh38 Chromosome 11, 121292700: 121292700
9 SC5D NM_006918.4(SC5D): c.343+3A> G single nucleotide variant Uncertain significance rs186378511 GRCh37 Chromosome 11, 121175205: 121175205
10 SC5D NM_006918.4(SC5D): c.343+3A> G single nucleotide variant Uncertain significance rs186378511 GRCh38 Chromosome 11, 121304496: 121304496
11 SC5D NM_006918.4(SC5D): c.444+11T> C single nucleotide variant Uncertain significance rs760625340 GRCh37 Chromosome 11, 121177206: 121177206
12 SC5D NM_006918.4(SC5D): c.444+11T> C single nucleotide variant Uncertain significance rs760625340 GRCh38 Chromosome 11, 121306497: 121306497
13 SC5D NM_006918.4(SC5D): c.753C> T (p.Gly251=) single nucleotide variant Uncertain significance rs201959036 GRCh37 Chromosome 11, 121178074: 121178074
14 SC5D NM_006918.4(SC5D): c.753C> T (p.Gly251=) single nucleotide variant Uncertain significance rs201959036 GRCh38 Chromosome 11, 121307365: 121307365
15 SC5D NM_006918.4(SC5D): c.*81A> C single nucleotide variant Benign rs1061332 GRCh37 Chromosome 11, 121178302: 121178302
16 SC5D NM_006918.4(SC5D): c.*81A> C single nucleotide variant Benign rs1061332 GRCh38 Chromosome 11, 121307593: 121307593
17 SC5D NM_006918.4(SC5D): c.*512G> A single nucleotide variant Uncertain significance rs886047851 GRCh37 Chromosome 11, 121178733: 121178733
18 SC5D NM_006918.4(SC5D): c.*512G> A single nucleotide variant Uncertain significance rs886047851 GRCh38 Chromosome 11, 121308024: 121308024
19 SC5D NM_006918.4(SC5D): c.*598T> C single nucleotide variant Uncertain significance rs886047852 GRCh37 Chromosome 11, 121178819: 121178819
20 SC5D NM_006918.4(SC5D): c.*598T> C single nucleotide variant Uncertain significance rs886047852 GRCh38 Chromosome 11, 121308110: 121308110
21 SC5D NM_006918.4(SC5D): c.*981C> T single nucleotide variant Uncertain significance rs185962880 GRCh37 Chromosome 11, 121179202: 121179202
22 SC5D NM_006918.4(SC5D): c.*981C> T single nucleotide variant Uncertain significance rs185962880 GRCh38 Chromosome 11, 121308493: 121308493
23 SC5D NM_006918.4(SC5D): c.*1012T> C single nucleotide variant Uncertain significance rs886047853 GRCh37 Chromosome 11, 121179233: 121179233
24 SC5D NM_006918.4(SC5D): c.*1012T> C single nucleotide variant Uncertain significance rs886047853 GRCh38 Chromosome 11, 121308524: 121308524
25 SC5D NM_006918.4(SC5D): c.*1195A> G single nucleotide variant Uncertain significance rs182551279 GRCh37 Chromosome 11, 121179416: 121179416
26 SC5D NM_006918.4(SC5D): c.*1195A> G single nucleotide variant Uncertain significance rs182551279 GRCh38 Chromosome 11, 121308707: 121308707
27 SC5D NM_006918.4(SC5D): c.*1876G> T single nucleotide variant Uncertain significance rs151210671 GRCh37 Chromosome 11, 121180097: 121180097
28 SC5D NM_006918.4(SC5D): c.*1876G> T single nucleotide variant Uncertain significance rs151210671 GRCh38 Chromosome 11, 121309388: 121309388
29 SC5D NM_006918.4(SC5D): c.*2477C> G single nucleotide variant Uncertain significance rs886047860 GRCh37 Chromosome 11, 121180698: 121180698
30 SC5D NM_006918.4(SC5D): c.*2477C> G single nucleotide variant Uncertain significance rs886047860 GRCh38 Chromosome 11, 121309989: 121309989
31 SC5D NM_006918.4(SC5D): c.*2662G> A single nucleotide variant Uncertain significance rs7125671 GRCh38 Chromosome 11, 121310174: 121310174
32 SC5D NM_006918.4(SC5D): c.*2662G> A single nucleotide variant Uncertain significance rs7125671 GRCh37 Chromosome 11, 121180883: 121180883
33 SC5D NM_006918.4(SC5D): c.*2943C> T single nucleotide variant Uncertain significance rs781723851 GRCh37 Chromosome 11, 121181164: 121181164
34 SC5D NM_006918.4(SC5D): c.*2943C> T single nucleotide variant Uncertain significance rs781723851 GRCh38 Chromosome 11, 121310455: 121310455
35 SC5D NM_006918.4(SC5D): c.*2986C> T single nucleotide variant Likely benign rs141633273 GRCh37 Chromosome 11, 121181207: 121181207
36 SC5D NM_006918.4(SC5D): c.*2986C> T single nucleotide variant Likely benign rs141633273 GRCh38 Chromosome 11, 121310498: 121310498
37 SC5D NM_006918.4(SC5D): c.*3200G> A single nucleotide variant Uncertain significance rs886047865 GRCh37 Chromosome 11, 121181421: 121181421
38 SC5D NM_006918.4(SC5D): c.*3200G> A single nucleotide variant Uncertain significance rs886047865 GRCh38 Chromosome 11, 121310712: 121310712
39 SC5D NM_006918.4(SC5D): c.*3345C> T single nucleotide variant Likely benign rs79862582 GRCh37 Chromosome 11, 121181566: 121181566
40 SC5D NM_006918.4(SC5D): c.*3345C> T single nucleotide variant Likely benign rs79862582 GRCh38 Chromosome 11, 121310857: 121310857
41 SC5D NM_006918.4(SC5D): c.*5224A> G single nucleotide variant Likely benign rs76249891 GRCh37 Chromosome 11, 121183445: 121183445
42 SC5D NM_006918.4(SC5D): c.*5224A> G single nucleotide variant Likely benign rs76249891 GRCh38 Chromosome 11, 121312736: 121312736
43 SC5D NM_006918.4(SC5D): c.*5282C> T single nucleotide variant Uncertain significance rs73017154 GRCh37 Chromosome 11, 121183503: 121183503
44 SC5D NM_006918.4(SC5D): c.*5282C> T single nucleotide variant Uncertain significance rs73017154 GRCh38 Chromosome 11, 121312794: 121312794
45 SC5D NM_006918.4(SC5D): c.*5329G> C single nucleotide variant Uncertain significance rs886047880 GRCh37 Chromosome 11, 121183550: 121183550
46 SC5D NM_006918.4(SC5D): c.*5329G> C single nucleotide variant Uncertain significance rs886047880 GRCh38 Chromosome 11, 121312841: 121312841
47 SC5D NM_006918.4(SC5D): c.*5630C> T single nucleotide variant Uncertain significance rs886047881 GRCh37 Chromosome 11, 121183851: 121183851
48 SC5D NM_006918.4(SC5D): c.*5630C> T single nucleotide variant Uncertain significance rs886047881 GRCh38 Chromosome 11, 121313142: 121313142
49 SC5D NM_006918.4(SC5D): c.*5640T> C single nucleotide variant Uncertain significance rs886047882 GRCh37 Chromosome 11, 121183861: 121183861
50 SC5D NM_006918.4(SC5D): c.*5640T> C single nucleotide variant Uncertain significance rs886047882 GRCh38 Chromosome 11, 121313152: 121313152

Expression for Lathosterolosis

Search GEO for disease gene expression data for Lathosterolosis.

Pathways for Lathosterolosis

Pathways related to Lathosterolosis according to KEGG:

37
# Name Kegg Source Accession
1 Steroid biosynthesis hsa00100

GO Terms for Lathosterolosis

Sources for Lathosterolosis

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
Content
Loading form....