Lathosterolosis: A Disorder of Cholesterol Biosynthesis Resembling Smith-Lemli-Opitz Syndrome

Ho, Alvin Chi Chung; Fung, Cheuk‐Wing; Siu, Tak-Shing; K., O. C.; Lam, Ching Wan; Tam, S; Wong, Virginia

doi:10.1007/8904_2013_255

Cited by 26 publications

(33 citation statements)

References 7 publications

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“…Their clinical phenotype is very similar to SLO syndrome, and <20 patients have been reported (Rossi et al 2007 and. An increase in lathosterol has been reported in plasma of a patient affected with lathosterolosis at 22 months of age (lathosterol = 81.6 μmol/ L; reference values <18 μmol/L) (Ho et al 2014). An increase in desmosterol has been reported in the plasma of patients affected with desmosterolosis (117-328 μmol/L; controls 1.3 ±0.8μmol/L) (Andersson et al 2002;Zolotushko et al 2011).…”

Section: Disorders Of Postsqualene Cholesterol Biosynthesismentioning

confidence: 81%

Antenatal manifestations of inborn errors of metabolism: biological diagnosis

Vianey‐Saban

Acquaviva

Cheillan

et al. 2016

J of Inher Metab Disea

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Inborn errors of metabolism (IEMs) that present with abnormal imaging findings in the second half of pregnancy are mainly lysosomal storage disorders (LSDs), cholesterol synthesis disorders (CSDs), glycogen storage disorder type IV (GSD IV), peroxisomal disorders, mitochondrial fatty acid oxidation defects (FAODs), organic acidurias, aminoacidopathies, congenital disorders of glycosylation (CDGs), and transaldolase deficiency. Their biological investigation requires fetal material. The supernatant of amniotic fluid (AF) is useful for the analysis of mucopolysaccharides, oligosaccharides, sialic acid, lysosphingolipids and some enzyme activities for LSDs, 7- and 8-dehydrocholesterol, desmosterol and lathosterol for CSDs, acylcarnitines for FAODs, organic acids for organic acidurias, and polyols for transaldolase deficiency. Cultured AF or fetal cells allow the measurement of enzyme activities for most IEMs, whole-cell assays, or metabolite measurements. The cultured cells or tissue samples taken after fetal death can be used for metabolic profiling, enzyme activities, and DNA extraction. Fetal blood can also be helpful. The identification of vacuolated cells orients toward an LSD, and plasma is useful for diagnosing peroxisomal disorders, FAODs, CSDs, some LSDs, and possibly CDGs and aminoacidopathies. We investigated AF of 1700 pregnancies after exclusion of frequent etiologies of nonimmune hydrops fetalis and identified 108 fetuses affected with LSDs (6.3 %), 29 of them with mucopolysaccharidosis type VII (MPS VII), and six with GSD IV (0.3 %). In the AF of 873 pregnancies, investigated because of intrauterine growth restriction and/or abnormal genitalia, we diagnosed 32 fetuses affected with Smith-Lemli-Opitz syndrome (3.7 %).

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Section: Disorders Of Postsqualene Cholesterol Biosynthesismentioning

confidence: 81%

Antenatal manifestations of inborn errors of metabolism: biological diagnosis

Vianey‐Saban

Acquaviva

Cheillan

et al. 2016

J of Inher Metab Disea

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“…Dietary cholesterol increases production of inflammatory indicators (IL-4 and IFN-γ) in lung lymphocytes in mice [29]. The two genes ( SC5D and DHCR7 ) with altered gene expression regulation are required for the final steps of cholesterol biosynthesis (Table 2) [30,31]. Therefore, altered cholesterol metabolism could also contribute to the inflammatory symptoms in horses after inhalation of hay dust.…”

Section: Discussionmentioning

confidence: 99%

PBMC Treatment Significantly Changes Gene Expression Regulation in Horses

Leeb

Gerber

2019

Preprint

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Expression quantitative trait loci (eQTLs) are context dependent, and therefore change 12 between tissues, cell types, and after cell treatment. In addition, SNP positions and RNAseq counts 13 must be updated after assembly of new reference genome sequences. Therefore, we remapped 14 eQTLs with Matrix eQTL using the previously generated and publicly available data from four 15 contexts of peripheral blood mononuclear cells (PBMCs) from European Warmblood horses to the 16 EquCab3.0 reference genome, and used a linear mixed model in R to identify eQTLs with 17 significantly different gene expression regulation in treated PBMCs when compared to no treatment 18 (baseline). We found no evidence that SNPs associated with significant changes in gene expression 19 between MCK and a treatment in PBMCs caused strong opposing regulatory effects. We identified 20 canonical pathways with a significant number of genes in PBMCs with altered gene expression 21 regulation when treated with lipopolysaccharides (LPS) and hay-dust extract (HDE). Significant 22 pathways included RhoA signaling in LPS, as well as histamine degradation, cholesterol 23 biosynthesis, FcγRIIB signaling, and others in HDE. Our results support previous research 24 indicating that pathways altered between baseline and treatment of PBMCs in horses with LPS or 25 HDE affect inflammatory responses through RhoA, B-cell signaling, IL-4 and IFN-γ, and histamine.26

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“…One child, who had severe cholestatic liver disease, developed osteoporosis causing pathological fractures [52,[60][61][62][63][64].…”

Section: Lathosterolosismentioning

confidence: 99%

Radiographic features of the skeleton in disorders of post-squalene cholesterol biosynthesis

et al. 2015

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Disorders of post-squalene cholesterol biosynthesis are inborn errors of metabolism characterised by multiple congenital abnormalities, including significant skeletal involvement. The most frequent and best-characterised example is the Smith-Lemli-Opitz syndrome. Nine other disorders are known, namely autosomal-recessive Antley-Bixler syndrome, Greenberg dysplasia, X-linked dominant chondrodysplasia punctata, X-linked recessive male emopamil-binding protein deficiency, CHILD syndrome, CK syndrome, sterol C4 methyloxidase-like deficiency, desmosterolosis and lathosterolosis. This study provides an overview of the radiologic features observed in these diseases. A common pattern of limb abnormalities is recognisable, including polydactyly, which is typically post-axial and rarely interdigital and can involve all four limbs, and syndactyly of the toes. Chondrodysplasia punctata is specifically associated with a subgroup of disorders of cholesterol biosynthesis (Greenberg dysplasia, CHILD syndrome, X-linked dominant chondrodysplasia punctata, male emopamil-binding protein deficiency). The possible occurrence of epiphyseal stippling in the Smith-Lemli-Opitz syndrome, initially reported, does not appear to be confirmed. Stippling is also associated with other congenital disorders such as chromosomal abnormalities, brachytelephalangic chondrodysplasia punctata (X-linked recessive chondrodysplasia punctata, disruptions of vitamin K metabolism, maternal autoimmune diseases), rhizomelic chondrodysplasia punctata (peroxisomal disorders) and lysosomal storage disorders. In the differential diagnosis of epiphyseal stippling, a moth-eaten appearance of bones, asymmetry, or presence of a common pattern of limb abnormalities indicate inborn errors of cholesterol biosynthesis. We highlight the specific differentiating radiologic features of disorders of post-squalene cholesterol biosynthesis.

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Lathosterolosis: A Disorder of Cholesterol Biosynthesis Resembling Smith-Lemli-Opitz Syndrome

Abstract: Lathosterolosis is an inborn error of cholesterol biosynthesis due to deficiency of the enzyme 3-betahydroxysteroid-delta-5-desaturase (or sterol-

Cited by 26 publications

References 7 publications

Antenatal manifestations of inborn errors of metabolism: biological diagnosis

Antenatal manifestations of inborn errors of metabolism: biological diagnosis

PBMC Treatment Significantly Changes Gene Expression Regulation in Horses

Radiographic features of the skeleton in disorders of post-squalene cholesterol biosynthesis

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