MCID: LTH002
MIFTS: 33

Lathosterolosis

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Lathosterolosis

MalaCards integrated aliases for Lathosterolosis:

Name: Lathosterolosis 54 50 24 56 71 29 13 52 69
Sterol C5-Desaturase Deficiency 50 24 56
Sc5d Deficiency 50 24
Lathst 71

Characteristics:

Orphanet epidemiological data:

56
lathosterolosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
lathosterolosis:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Inborn errors of metabolism


Summaries for Lathosterolosis

NIH Rare Diseases : 50 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. last updated: 11/19/2014

MalaCards based summary : Lathosterolosis, also known as sterol c5-desaturase deficiency, is related to smith-lemli-opitz syndrome and greenberg skeletal dysplasia, and has symptoms including failure to thrive, myoclonus and bulbous nose. An important gene associated with Lathosterolosis is SC5D (Sterol-C5-Desaturase). The drug Phytosterol has been mentioned in the context of this disorder. Affiliated tissues include liver, kidney and testes.

UniProtKB/Swiss-Prot : 71 Lathosterolosis: Autosomal recessive disorder characterized by a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease.

Wikipedia : 72 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:

id Related Disease Score Top Affiliating Genes
1 smith-lemli-opitz syndrome 11.2
2 greenberg skeletal dysplasia 10.8
3 cataract 9.8

Symptoms & Phenotypes for Lathosterolosis

Symptoms via clinical synopsis from OMIM:

54

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

Head And Neck- Eyes:
ptosis
epicanthal folds
cataract

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

Skeletal:
osteoporosis
pathologic fracture

Head And Neck- Ears:
conductive hearing loss

Hematology:
schistocytes
anisopoikilocytosis
large platelets
acanthocytes
vacuolated monocytes

Abdomen- Biliary Tract:
bilobate gallbladder

Skeletal- Spine:
sagittal vertebral cleft

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

Head And Neck- Head:
microcephaly

Head And Neck- Nose:
anteverted nares
broad nasal bridge

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

Abdomen- Liver:
intrahepatic cholestasis

Genitourinary- Kidneys:
pyelectasis

Skeletal- Hands:
postaxial hexadactyly


Clinical features from OMIM:

607330

Human phenotypes related to Lathosterolosis:

56 32 (show top 50) (show all 69)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 56 32 frequent (33%) Frequent (79-30%) HP:0001508
2 myoclonus 56 32 frequent (33%) Frequent (79-30%) HP:0001336
3 bulbous nose 56 32 frequent (33%) Frequent (79-30%) HP:0000414
4 hepatomegaly 56 32 frequent (33%) Frequent (79-30%) HP:0002240
5 seizures 56 32 very rare (1%) Frequent (79-30%) HP:0001250
6 ptosis 56 32 very rare (1%) Frequent (79-30%) HP:0000508
7 microcephaly 56 32 very rare (1%) Very frequent (99-80%) HP:0000252
8 thrombocytopenia 56 32 frequent (33%) Frequent (79-30%) HP:0001873
9 micrognathia 56 32 very rare (1%) Frequent (79-30%) HP:0000347
10 intrauterine growth retardation 56 32 frequent (33%) Frequent (79-30%) HP:0001511
11 sloping forehead 56 32 very rare (1%) Frequent (79-30%) HP:0000340
12 short nose 56 32 very rare (1%) Frequent (79-30%) HP:0003196
13 anteverted nares 56 32 very rare (1%) Frequent (79-30%) HP:0000463
14 global developmental delay 56 32 hallmark (90%) Very frequent (99-80%) HP:0001263
15 microcornea 56 32 frequent (33%) Frequent (79-30%) HP:0000482
16 cataract 56 32 very rare (1%) Very frequent (99-80%) HP:0000518
17 long philtrum 56 32 very rare (1%) Frequent (79-30%) HP:0000343
18 full cheeks 56 32 frequent (33%) Frequent (79-30%) HP:0000293
19 horseshoe kidney 56 32 very rare (1%) Frequent (79-30%) HP:0000085
20 toe syndactyly 56 32 very rare (1%) Frequent (79-30%) HP:0001770
21 hepatic failure 56 32 frequent (33%) Frequent (79-30%) HP:0001399
22 downslanted palpebral fissures 56 32 very rare (1%) Frequent (79-30%) HP:0000494
23 narrow forehead 56 32 very rare (1%) Frequent (79-30%) HP:0000341
24 high palate 56 32 very rare (1%) Frequent (79-30%) HP:0000218
25 epicanthus 56 32 very rare (1%) Frequent (79-30%) HP:0000286
26 muscular hypotonia 56 32 very rare (1%) Frequent (79-30%) HP:0001252
27 anisopoikilocytosis 56 32 very rare (1%) Frequent (79-30%) HP:0004823
28 downturned corners of mouth 56 32 frequent (33%) Frequent (79-30%) HP:0002714
29 intrahepatic cholestasis 56 32 very rare (1%) Frequent (79-30%) HP:0001406
30 talipes 56 32 frequent (33%) Frequent (79-30%) HP:0001883
31 hearing impairment 56 32 frequent (33%) Frequent (79-30%) HP:0000365
32 cerebral calcification 56 32 frequent (33%) Frequent (79-30%) HP:0002514
33 arnold-chiari malformation 56 32 very rare (1%) Frequent (79-30%) HP:0002308
34 biparietal narrowing 56 32 frequent (33%) Frequent (79-30%) HP:0004422
35 meningocele 56 32 frequent (33%) Frequent (79-30%) HP:0002435
36 gingival overgrowth 56 32 very rare (1%) Frequent (79-30%) HP:0000212
37 prominent metopic ridge 56 32 frequent (33%) Frequent (79-30%) HP:0005487
38 hypoplasia of penis 56 32 hallmark (90%) Very frequent (99-80%) HP:0008736
39 opacification of the corneal stroma 56 32 very rare (1%) Frequent (79-30%) HP:0007759
40 specific learning disability 56 32 hallmark (90%) Very frequent (99-80%) HP:0001328
41 abnormal platelet morphology 56 32 frequent (33%) Frequent (79-30%) HP:0011875
42 postaxial hand polydactyly 56 32 very rare (1%) Frequent (79-30%) HP:0001162
43 postaxial foot polydactyly 56 32 very rare (1%) Very frequent (99-80%) HP:0001830
44 cerebellar cortical atrophy 56 32 frequent (33%) Frequent (79-30%) HP:0008278
45 abnormality of the thoracic spine 56 32 frequent (33%) Frequent (79-30%) HP:0100711
46 cerebral atrophy 32 very rare (1%) HP:0002059
47 osteoporosis 32 very rare (1%) HP:0000939
48 talipes equinovarus 32 very rare (1%) HP:0001762
49 intellectual disability 32 very rare (1%) HP:0001249
50 thin vermilion border 32 very rare (1%) HP:0000233

Drugs & Therapeutics for Lathosterolosis

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


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

Interventional clinical trials:


id 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:

id Genetic test Affiliating Genes
1 Lathosterolosis 29 24 SC5D

Anatomical Context for Lathosterolosis

MalaCards organs/tissues related to Lathosterolosis:

39
Liver, Kidney, Testes, Skin, Monocytes

Publications for Lathosterolosis

Articles related to Lathosterolosis:

id 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:

71
id 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
id 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.632G> A (p.Gly211Asp) single nucleotide variant Pathogenic rs104894296 GRCh37 Chromosome 11, 121177953: 121177953
3 SC5D NM_006918.4(SC5D): c.137A> C (p.Tyr46Ser) single nucleotide variant Pathogenic rs104894297 GRCh37 Chromosome 11, 121174221: 121174221

Expression for Lathosterolosis

Search GEO for disease gene expression data for Lathosterolosis.

Pathways for Lathosterolosis

GO Terms for Lathosterolosis

Sources for Lathosterolosis

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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