Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001721
Status:
COMPLETED
Last Update Posted:
2024-07-12
First Post:
1999-11-03
Brief Title:
Study of Smith-Lemli-Opitz Syndrome
Sponsor:
Eunice Kennedy Shriver National Institute of Child Health and Human Development NICHD
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Clinical and Basic Investigations Into Smith-Lemli-Opitz Syndrome
Status:
COMPLETED
Status Verified Date:
2024-01-22
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Smith-Lemli-Opitz Syndrome SLOS is a genetic disorder autosomal recessive caused by an abnormality in the production of cholesterol The disorder can occur in both a mild or severe form SLOS is associated with multiple birth defects and mental retardation Some of the birth defects include abnormal facial features poor muscle tone poor growth shortened life span and abnormalities of the heart lungs brain gastrointestinal tract limbs genitalia and kidneys
There is no known cure for SLOS but recently patients have been treated with increased amounts of cholesterol in their diet The cholesterol in a persons diet is unable to correct the abnormalities in the patients organs but researchers hope it will improve growth failure and mental retardation
This study was developed to answer questions about the causes and complications of SLOS as well as the effectiveness of cholesterol treatment The study will enroll patients diagnosed with SLOS and their mothers The objectives of the study will be to address the following questions
1 TAB What is the prognosis natural history of the demyelination in the nervous system of patients with SLOS
2 TAB Do patients with SLOS have other problems concerning the function of their endocrine systems
3 TABWhat are the genetic make-ups of patients with SLOS
4 TABCan further studies of cholesterol metabolism and genetic testing using SLOS fibroblasts increase the understanding of SLOSTAB
There is no known cure for SLOS but recently patients have been treated with increased amounts of cholesterol in their diet The cholesterol in a persons diet is unable to correct the abnormalities in the patients organs but researchers hope it will improve growth failure and mental retardation
This study was developed to answer questions about the causes and complications of SLOS as well as the effectiveness of cholesterol treatment The study will enroll patients diagnosed with SLOS and their mothers The objectives of the study will be to address the following questions
1 TAB What is the prognosis natural history of the demyelination in the nervous system of patients with SLOS
2 TAB Do patients with SLOS have other problems concerning the function of their endocrine systems
3 TABWhat are the genetic make-ups of patients with SLOS
4 TABCan further studies of cholesterol metabolism and genetic testing using SLOS fibroblasts increase the understanding of SLOSTAB
Detailed Description:
Smith-Lemli-Opitz syndrome SLOS is an autosomal recessive multiple congenital anomalymental retardation syndrome Typical clinical features include a distinctive facial appearance mental retardation autistic behavior hypotonia failure to feed poor growth decreased life span and variable structural anomalies of the heart lungs brain gastrointestinal tract limbs genitalia and kidneys The SLOS phenotypic spectrum is broad and variable At the severe end of the spectrum SLOS is a lethal disorder with multiple major congenital anomalies whereas mild cases of SLOS present with a combination of minor physical stigmata behavioral problems and learning disabilities SLOS is due to an inborn error of cholesterol biosynthesis Biochemically SLOS patients have a deficiency of 3beta-hydroxysterol delta7-reductase activity 3beta-hydroxysterol delta7-reductase is an NADPH dependent microsomal enzyme that catalyzes the reduction of the C78 double bond of 7-dehydrocholesterol 7-DHC to yield cholesterol in the last step of cholesterol biosynthesis via the Kandutsch-Russel pathway This inborn error of cholesterol biosynthesis results in elevated tissue and serum 7-DHC levels and typically decreased serum and tissue cholesterol levels In 1998 we established that the deficiency in 3beta-hydroxysterol delta7-reductase activity is due to mutation of the 3beta-hydroxysterol delta7-reductase gene DHCR7 Once the biochemical defect in SLOS was identified dietary cholesterol supplementation was proposed and employed as a therapeutic approach Although developmental malformations remain fixed dietary cholesterol supplementation appears to improve the overall health of these patients and initial results have shown that dietary cholesterol supplementation has had a positive impact on some of the behavioral manifestations of this disorder Although our understanding of this disorder has advanced over the last few years many questions remain concerning the effectiveness of cholesterol replacement therapy the long term prognosis for individuals on dietary cholesterol supplementation and the need for adjunctive measures in the clinical management of SLOS patients We propose to answer some of these questions by continuing our longitudinal natural historyprognosis study on patients with SLOS We also plan on studying very closely related disorders such as lathosterolosis under this protocol Lathosterolosis is caused by a deficiency in the enzyme sterol 3-beta-hydroxysteroid-delta-5-desaturase which is necessary for the conversion of lathosterol into 7-DHC The clinical picture is very similar to SLOS with prominent features including microcephaly ptosis bilateral 23 toe syndactyly Lathosterolosis is also inherited in an autosomal recessive manner Lethosterolosis is extremely rare with only 4 cases described in the literature so far and an estimated incidence of less than 1 in a million The below objectives protocol evaluations risks benefits and other pertinent issues apply to SLOS and lathosterolosis even if lathosterolosis is not explicitly named
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 98-CH-0081 | None | None | None |