MCID: LTH002
MIFTS: 34

Lathosterolosis

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Lathosterolosis

MalaCards integrated aliases for Lathosterolosis:

Name: Lathosterolosis 53 49 55 71 36 28 13 51 69
Sterol C5-Desaturase Deficiency 53 49 55
Sc5d Deficiency 53 49
Lathst 71

Characteristics:

Orphanet epidemiological data:

55
lathosterolosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
lathosterolosis:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Inborn errors of metabolism


Summaries for Lathosterolosis

NIH Rare Diseases : 49 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 dysplasia, and has symptoms including seizures, myoclonus and high palate. 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.

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:

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

Symptoms & Phenotypes for Lathosterolosis

Symptoms via clinical synopsis from OMIM:

53
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

Genitourinary Kidneys:
pyelectasis

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

Abdomen Biliary Tract:
bilobate gallbladder

Skeletal Spine:
sagittal vertebral cleft


Clinical features from OMIM:

607330

Human phenotypes related to Lathosterolosis:

55 31 (show top 50) (show all 70)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 very rare (1%) Frequent (79-30%) HP:0001250
2 myoclonus 55 31 frequent (33%) Frequent (79-30%) HP:0001336
3 high palate 55 31 very rare (1%) Frequent (79-30%) HP:0000218
4 ptosis 55 31 very rare (1%) Frequent (79-30%) HP:0000508
5 muscular hypotonia 55 31 very rare (1%) Frequent (79-30%) HP:0001252
6 failure to thrive 55 31 frequent (33%) Frequent (79-30%) HP:0001508
7 cerebral calcification 55 31 frequent (33%) Frequent (79-30%) HP:0002514
8 gingival overgrowth 55 31 very rare (1%) Frequent (79-30%) HP:0000212
9 hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000365
10 cataract 55 31 very rare (1%) Very frequent (99-80%) HP:0000518
11 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
12 hepatomegaly 55 31 frequent (33%) Frequent (79-30%) HP:0002240
13 short nose 55 31 very rare (1%) Frequent (79-30%) HP:0003196
14 microcephaly 55 31 very rare (1%) Very frequent (99-80%) HP:0000252
15 anteverted nares 55 31 very rare (1%) Frequent (79-30%) HP:0000463
16 full cheeks 55 31 frequent (33%) Frequent (79-30%) HP:0000293
17 long philtrum 55 31 very rare (1%) Frequent (79-30%) HP:0000343
18 micrognathia 55 31 very rare (1%) Frequent (79-30%) HP:0000347
19 opacification of the corneal stroma 55 31 very rare (1%) Frequent (79-30%) HP:0007759
20 epicanthus 55 31 very rare (1%) Frequent (79-30%) HP:0000286
21 biparietal narrowing 55 31 frequent (33%) Frequent (79-30%) HP:0004422
22 intrauterine growth retardation 55 31 frequent (33%) Frequent (79-30%) HP:0001511
23 specific learning disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001328
24 horseshoe kidney 55 31 very rare (1%) Frequent (79-30%) HP:0000085
25 thrombocytopenia 55 31 frequent (33%) Frequent (79-30%) HP:0001873
26 arnold-chiari malformation 55 31 very rare (1%) Frequent (79-30%) HP:0002308
27 downslanted palpebral fissures 55 31 very rare (1%) Frequent (79-30%) HP:0000494
28 meningocele 55 31 frequent (33%) Frequent (79-30%) HP:0002435
29 downturned corners of mouth 55 31 frequent (33%) Frequent (79-30%) HP:0002714
30 bulbous nose 55 31 frequent (33%) Frequent (79-30%) HP:0000414
31 hypoplasia of penis 55 31 hallmark (90%) Very frequent (99-80%) HP:0008736
32 abnormal platelet morphology 55 31 frequent (33%) Frequent (79-30%) HP:0011875
33 hepatic failure 55 31 frequent (33%) Frequent (79-30%) HP:0001399
34 toe syndactyly 55 31 very rare (1%) Frequent (79-30%) HP:0001770
35 microcornea 55 31 frequent (33%) Frequent (79-30%) HP:0000482
36 postaxial hand polydactyly 55 31 very rare (1%) Frequent (79-30%) HP:0001162
37 postaxial foot polydactyly 55 31 very rare (1%) Very frequent (99-80%) HP:0001830
38 sloping forehead 55 31 very rare (1%) Frequent (79-30%) HP:0000340
39 talipes 55 31 frequent (33%) Frequent (79-30%) HP:0001883
40 prominent metopic ridge 55 31 frequent (33%) Frequent (79-30%) HP:0005487
41 intrahepatic cholestasis 55 31 very rare (1%) Frequent (79-30%) HP:0001406
42 narrow forehead 55 31 very rare (1%) Frequent (79-30%) HP:0000341
43 anisopoikilocytosis 55 31 very rare (1%) Frequent (79-30%) HP:0004823
44 cerebellar cortical atrophy 55 31 frequent (33%) Frequent (79-30%) HP:0008278
45 abnormality of the thoracic spine 55 31 frequent (33%) Frequent (79-30%) HP:0100711
46 hepatosplenomegaly 31 very rare (1%) HP:0001433
47 intellectual disability 31 very rare (1%) HP:0001249
48 wide nasal bridge 31 very rare (1%) HP:0000431
49 osteoporosis 31 very rare (1%) HP:0000939
50 pathologic fracture 31 very rare (1%) HP:0002756

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 28 SC5D

Anatomical Context for Lathosterolosis

MalaCards organs/tissues related to Lathosterolosis:

38
Liver, Kidney, Skin, Testes, Monocytes

Publications for Lathosterolosis

Articles related to Lathosterolosis:

# Title Authors Year
1
Lathosterolosis: a disorder of cholesterol biosynthesis resembling smith-lemli-opitz syndrome. ( 24142275 )
2014
2
Liver transplantation in defects of cholesterol biosynthesis: the case of lathosterolosis. ( 24621408 )
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
# 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
# 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

Pathways related to Lathosterolosis according to KEGG:

36
# 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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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