Sterols
| Label Mnemonic: | STERL |
| Epic code: | LAB7475 |
| Downtime form: | A-1a Doctor/Provider Orders - Pathology Core and Specialty Care Nursery |
Commercial Mailout Laboratory
6240-8 RCP
356-8593
6240-8 RCP
356-8593
Specimen(s):
Plasma
Collection Medium:
 |
| Green top tube 4 mL (Na Heparin) |
Minimum:
Preferred Minimum: 0.5 mL plasma
Absolute Minimum: 0.2 mL plasma
Fasting (12 hours or more, infants just before next feeding).
Note: Patient's age and sex are required.
Absolute Minimum: 0.2 mL plasma
Fasting (12 hours or more, infants just before next feeding).
Note: Patient's age and sex are required.
Rejection Criteria:
Specimens other than plasma.
Turn Around
Time:
2-7 days upon receipt at reference laboratory
Reference Range:
7-DEHYDROCHOLESTEROL < or = 2.0 mg/L 8-DEHYDROCHOLESTEROL < or = 0.3 mg/L 8(9)-CHOLESTENOL < or = 5.0 mg/L CAMPESTEROL < or = 8.0 mg/L CHOLESTANOL < or = 6.0 mg/L DESMOSTEROL < or = 2.5 mg/L DIHYDRO T-MAS < or = 0.3 mg/L LATHOSTEROL < or = 6.0 mg/L SITOSTEROL < or = 15.0 mg/L SQUALENE < or = 1.0 mg/L STIGMASTEROL < or = 0.5 mg/L Cautions: Reference ranges were derived using fasting specimens from healthy individuals. Sitosterol and campesterol values may be mildly elevated in individuals whose diets include foods with high concentrations of plant sterols, such as some vegetable oils and infant formulas.
Interpretive Data:
A quantitative report of the patient's sterol profile and a Biochemical Genetics consultant's interpretation is provided for each specimen.
Comments:
Please print, complete and submit the Informed Consent for Genetic Testing to the lab, with the specimen.
This is a screening test for disorders of cholesterol biosynthesis including desmosterolosis, lathosterolosis, cerebrotendinous xanthomatosis, sitosterolemia, sterol C4 methyl oxidase deficiency, and EBP gene disorders (X-linked dominant chondrodysplasia punctata type 2 [CDPX2], male EBP disorder with neurologic defects [MEND]).
Multiple analytes including but not limited to 7-dehydrocholesterol (7-DHC), 8-dehydrocholesterol (8-DHC), desmosterol, lathosterol, campesterol, sitosterol, and cholestanol are included in this test.
Clinical Information:
Cholesterol plays an essential role in many cellular and developmental processes. In addition to its role as a membrane lipid, it is the precursor to numerous molecules that play an important role in cell growth and differentiation, protein glycosylation, and signaling pathways. The biosynthesis of cholesterol and its subsequent conversion to other essential compounds is complex, involving a number of intermediates and enzymes. Disorders that result from a deficiency of these enzymes lead to an accumulation of specific intermediates and inhibit the formation of important biomolecules. Clinical findings common to cholesterol biosynthesis disorders include congenital skeletal malformations, dysmorphic facial features, psychomotor retardation, and failure to thrive.
Desmosterolosis (desmosterol reductase deficiency) is a very rare disorder of cholesterol biosynthesis with a clinical phenotype similar to that of Smith-Lemli-Opitz (SLO) syndrome (7-dehydrocholesterol reductase deficiency). It is caused by variants in DHCR24 (3-beta-hydroxysterol delta-24-reductase). To date, less than 20 cases of desmosterolosis have been described. Its biochemical marker is the marked elevation of desmosterol in plasma, tissue, and cultured cells.
Another very rare disorder of cholesterol biosynthesis is lathosterolosis caused by variants in SC5DL (sterol 3-beta-hydroxysteroid-delta-5-desaturase). Less than 20 patients have been described to date, but the phenotype appears to be characterized by dysmorphic features, multiple congenital anomalies including those of limb and kidney, intellectual disability, and liver disease. Biochemical abnormalities include elevated lathosterol and transaminases, hyperbilirubinemia, and absent 7-dehydrocholesterol.
Sitosterolemia is a rare autosomal recessive disorder caused by variants in the ATP-binding cassette (ABC) transporter genes, ABCG5 and ABCG8, which abnormally enhance the absorption of plant sterols and cholesterol from the intestines. Patients often present with hematologic abnormalities and tendon and tuberous xanthomas as well as premature coronary artery disease. A biochemical diagnosis of sitosterolemia is made by documenting elevations of the plant sterols sitosterol and campesterol in plasma or serum.
Cerebrotendinous xanthomatosis (CTX), also known as 27-hydroxylase deficiency, is caused by variants in the CYP27A1 gene. CTX is an autosomal recessive sterol storage disease resulting in the accumulation of cholestanol and cholesterol in most tissues and markedly increased levels of cholestanol in serum. Additionally the ketosterol bile acid precursors (7-alpha-hydroxy-4-cholesten-3-one [7a-C4] and 7-alpha,12-alpha–dihydroxycholest-4-en-3-one [7a12aC4]) are elevated in multiple tissues throughout the body and can be measured in blood or plasma, see:
-CTXBS / Cerebrotendinous Xanthomatosis, Blood Spot
-CTXWB / Cerebrotendinous Xanthomatosis, Blood
-CTXP / Cerebrotendinous Xanthomatosis, Plasma
Clinical symptoms, which are variable, develop gradually and can include early chronic diarrhea, followed by bilateral cataracts, tuberous and tendon xanthomas, early atherosclerosis, and progressive neurologic impairment such as ataxia, paraparesis, cerebellar ataxia, and dementia. CTX should be suspected in patients with tendon xanthomas and normal or elevated serum cholesterol, and considered in cases of unexplained juvenile cataracts.
X-linked chondrodysplasia punctata 2 (CDPX2) and MEND (male EBP disorder with neurologic defects) syndrome are caused by defects in EBP, which codes for emopamil binding protein, an important enzyme in the final steps of the sterol biosynthesis pathway. CDPX2 is a typically male-lethal X-linked dominant skeletal dysplasia with accompanying skin, hair, nail, and eye abnormalities (ichthyosis in the newborn, scarring alopecia, cataracts). The phenotype in affected female patients is variable ranging from severe skeletal and internal anomalies leading to fetal demise or stillbirth to milder short stature or even asymptomatic carriers.
MEND syndrome, caused by nonmosaic partial loss of function variants in EBP, affects primarily male patients. It is a neurologic phenotype characterized by moderate-to-severe developmental delay and central nervous system malformations, in particular Dandy-Walker malformation, agenesis of the corpus callosum, and hydrocephalus. Many patients have dysmorphic features that overlap with Smith-Lemli-Opitz syndrome (2-3 toe syndactyly, postaxial polydactyly, and urogenital anomalies). Female patients are rarely affected.
Biochemical abnormalities for CDXP2 and MEND syndrome include elevated 8(9)-cholestenol and 8-dehydrocholesterol.
Sterol C4 methyl oxidase deficiency (SC4MOL) is an autosomal recessive inborn error of cholesterol metabolism characterized by microcephaly, congenital cataracts, and psoriasiform dermatitis. Other features include immune dysregulation, joint pain, short stature, and intellectual disability. Biochemical abnormalities include increased plasma 4,4'-dimethyl and 4alpha-monomethylsterols such as dihydro T-MAS (4,4'-dimethyl-5alpha-cholesta-8(9)-en-3beta-ol), and decreased total, low-density lipoprotein, and high-density lipoprotein cholesterol.
This is a screening test for disorders of cholesterol biosynthesis including desmosterolosis, lathosterolosis, cerebrotendinous xanthomatosis, sitosterolemia, sterol C4 methyl oxidase deficiency, and EBP gene disorders (X-linked dominant chondrodysplasia punctata type 2 [CDPX2], male EBP disorder with neurologic defects [MEND]).
Multiple analytes including but not limited to 7-dehydrocholesterol (7-DHC), 8-dehydrocholesterol (8-DHC), desmosterol, lathosterol, campesterol, sitosterol, and cholestanol are included in this test.
Clinical Information:
Cholesterol plays an essential role in many cellular and developmental processes. In addition to its role as a membrane lipid, it is the precursor to numerous molecules that play an important role in cell growth and differentiation, protein glycosylation, and signaling pathways. The biosynthesis of cholesterol and its subsequent conversion to other essential compounds is complex, involving a number of intermediates and enzymes. Disorders that result from a deficiency of these enzymes lead to an accumulation of specific intermediates and inhibit the formation of important biomolecules. Clinical findings common to cholesterol biosynthesis disorders include congenital skeletal malformations, dysmorphic facial features, psychomotor retardation, and failure to thrive.
Desmosterolosis (desmosterol reductase deficiency) is a very rare disorder of cholesterol biosynthesis with a clinical phenotype similar to that of Smith-Lemli-Opitz (SLO) syndrome (7-dehydrocholesterol reductase deficiency). It is caused by variants in DHCR24 (3-beta-hydroxysterol delta-24-reductase). To date, less than 20 cases of desmosterolosis have been described. Its biochemical marker is the marked elevation of desmosterol in plasma, tissue, and cultured cells.
Another very rare disorder of cholesterol biosynthesis is lathosterolosis caused by variants in SC5DL (sterol 3-beta-hydroxysteroid-delta-5-desaturase). Less than 20 patients have been described to date, but the phenotype appears to be characterized by dysmorphic features, multiple congenital anomalies including those of limb and kidney, intellectual disability, and liver disease. Biochemical abnormalities include elevated lathosterol and transaminases, hyperbilirubinemia, and absent 7-dehydrocholesterol.
Sitosterolemia is a rare autosomal recessive disorder caused by variants in the ATP-binding cassette (ABC) transporter genes, ABCG5 and ABCG8, which abnormally enhance the absorption of plant sterols and cholesterol from the intestines. Patients often present with hematologic abnormalities and tendon and tuberous xanthomas as well as premature coronary artery disease. A biochemical diagnosis of sitosterolemia is made by documenting elevations of the plant sterols sitosterol and campesterol in plasma or serum.
Cerebrotendinous xanthomatosis (CTX), also known as 27-hydroxylase deficiency, is caused by variants in the CYP27A1 gene. CTX is an autosomal recessive sterol storage disease resulting in the accumulation of cholestanol and cholesterol in most tissues and markedly increased levels of cholestanol in serum. Additionally the ketosterol bile acid precursors (7-alpha-hydroxy-4-cholesten-3-one [7a-C4] and 7-alpha,12-alpha–dihydroxycholest-4-en-3-one [7a12aC4]) are elevated in multiple tissues throughout the body and can be measured in blood or plasma, see:
-CTXBS / Cerebrotendinous Xanthomatosis, Blood Spot
-CTXWB / Cerebrotendinous Xanthomatosis, Blood
-CTXP / Cerebrotendinous Xanthomatosis, Plasma
Clinical symptoms, which are variable, develop gradually and can include early chronic diarrhea, followed by bilateral cataracts, tuberous and tendon xanthomas, early atherosclerosis, and progressive neurologic impairment such as ataxia, paraparesis, cerebellar ataxia, and dementia. CTX should be suspected in patients with tendon xanthomas and normal or elevated serum cholesterol, and considered in cases of unexplained juvenile cataracts.
X-linked chondrodysplasia punctata 2 (CDPX2) and MEND (male EBP disorder with neurologic defects) syndrome are caused by defects in EBP, which codes for emopamil binding protein, an important enzyme in the final steps of the sterol biosynthesis pathway. CDPX2 is a typically male-lethal X-linked dominant skeletal dysplasia with accompanying skin, hair, nail, and eye abnormalities (ichthyosis in the newborn, scarring alopecia, cataracts). The phenotype in affected female patients is variable ranging from severe skeletal and internal anomalies leading to fetal demise or stillbirth to milder short stature or even asymptomatic carriers.
MEND syndrome, caused by nonmosaic partial loss of function variants in EBP, affects primarily male patients. It is a neurologic phenotype characterized by moderate-to-severe developmental delay and central nervous system malformations, in particular Dandy-Walker malformation, agenesis of the corpus callosum, and hydrocephalus. Many patients have dysmorphic features that overlap with Smith-Lemli-Opitz syndrome (2-3 toe syndactyly, postaxial polydactyly, and urogenital anomalies). Female patients are rarely affected.
Biochemical abnormalities for CDXP2 and MEND syndrome include elevated 8(9)-cholestenol and 8-dehydrocholesterol.
Sterol C4 methyl oxidase deficiency (SC4MOL) is an autosomal recessive inborn error of cholesterol metabolism characterized by microcephaly, congenital cataracts, and psoriasiform dermatitis. Other features include immune dysregulation, joint pain, short stature, and intellectual disability. Biochemical abnormalities include increased plasma 4,4'-dimethyl and 4alpha-monomethylsterols such as dihydro T-MAS (4,4'-dimethyl-5alpha-cholesta-8(9)-en-3beta-ol), and decreased total, low-density lipoprotein, and high-density lipoprotein cholesterol.
Methodology:
Gas Chromatography-Mass Spectrometry (GC-MS)
CPT Code:
82542
See Additional Information:
Fasting Specimen Requirements
Fasting Specimen Requirements