Lathosterolosis

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OMIM 57 607330 Orphanet 59 ORPHA46059 MESH via Orphanet 45 C537880 ICD10 via Orphanet 34 Q87.8 UMLS via Orphanet 74 C1846421

MedGen 42 C1846421 KEGG 37 H01281 SNOMED-CT via HPO 69 258211005 41729002 441787004 441798003 54711002 27272007 301348000 271611007 32958008 103276001 15188001 343087000 95828007 44057004 249321001 708670007 26098002 246800008 11934000 128306009 193570009 247053007 64859006 205131007 228156007 247578003 91138005 128613002 246545002 313307000 84757009 91175000 398151007 398152000 224958001 127324008 17450006 59927004 4637005 36760000 36440009 432788009 276617005 444896005 59576002 199612005 22033007 249808002 397932003 32113001 302215000 415116008 398309008 250249008 385472000 278849000 418143002 52522001 80515008 253184003 171131006 203994003 414667000 17944005 22640007 268029009 26165005 166603001 166643006 75183008 249310005 246957002 34911001 more UMLS 73 C1846421

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

Clinical features from OMIM:

607330

Search NIH Clinical Center for Lathosterolosis

Search GEO for disease gene expression data for Lathosterolosis.