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Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation

This study is currently recruiting participants.
Verified August 15, 2017 by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02089789
First Posted: March 18, 2014
Last Update Posted: October 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
  Purpose

Background:

- Proteins, fats, and other molecules are the body s building blocks. Many of these molecules must have sugars, or chains of sugars, attached to work properly. People with congenital disorders of glycosylation (CDGs) cannot attach these sugars or sugar chains properly. A child or adult with a CDG can have symptoms in different parts of the body, including brain, nerves, muscles, liver, and immune system. Researchers want to learn more about these diseases to understand better what is causing the problems.

Objective:

- To learn more about CDGs.

Eligibility:

- People age 1-80 with CDG or suspected to have a CDG.

Design:

  • CDG participants will stay in the hospital 3-5 days. They will have:
  • Medical history and physical exam. They will answer questions about their CDG.
  • Blood taken several times. Their skin will be numbed, then a needle will take blood from an arm vein.
  • Samples taken of their skin, urine, and maybe stool and spinal fluid.
  • Photos taken of their whole body. They can wear underwear and cover their eyes.
  • Brain MRI. They will lie on a table that slides in and out of a metal cylinder. The scanner makes loud knocking noises so they can wear earplugs.
  • Abdomen ultrasound. Sound waves take images of the body from the outside.
  • Hand/wrist X-rays for young patients. They may have a full-body X-ray.
  • DEXA bone density scan. Participants will lie on a table under a scanner.
  • Echocardiogram and electrocardiogram for heart activity. Pads are stuck on the skin and the electrical activity of the heart is recorded.
  • Tests of hearing, thinking, motor skills, and speech.
  • Children participants may have tests done under sedation if it will benefit them directly.
  • CDG participants may have other procedures during their visit. They may have follow-up visits every year.

Condition
Congenital Disorders of Glycosylation

Study Type: Observational
Study Design: Time Perspective: Other
Official Title: Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):

Primary Outcome Measures:
  • To delineate the clinical and laboratory findings of CDGs, defining the frequency and variability of multi-systemic manifestations in this group of disorders. [ Time Frame: 3 years ]

Estimated Enrollment: 100
Study Start Date: March 14, 2014
Estimated Study Completion Date: December 1, 2018
Estimated Primary Completion Date: December 1, 2017 (Final data collection date for primary outcome measure)
Detailed Description:
Congenital disorders of glycosylation (CDGs) are a group of diseases characterized by an abnormal glycosylation of proteins, but that can also result from an abnormal synthesis of glycosaminoglycans, glycophospholipids or glycosylphosphatidylinositol or the abnormal synthesis or utilization of dolichols. CDGs were first described in 1980, but the initial description of mutations in a gene underlying CDGs did not occur until 1997. Since then, there has been a rapid discovery phase of new CDGs, with more than 80 different types, reflecting defined mutations in 80 different genes in glycobiologic pathways affecting about 1000 patients worldwide. The clinical manifestations of CDGs are quite variable both within and among different types, and physicians from every specialty will likely encounter patients affected by glycosylation defects. The diagnosis of CDGs should be suspected in cases with neurological signs and symptoms of unknown etiology, or in any patient with multisystemic disease even in the absence of neurological features. Other potential clinical presentations include tissuespecific disorders such as anemia or ichthyosis, when common disorders have been ruled out. Diagnostic screening for many of the disorders is performed by analyzing the glycosylation on serum transferrin, initially by isoelectric focusing, now by mass spectrometry, in specialized clinical diagnostic laboratories both in the United States and abroad. The pattern of transferring glycoforms allows the differentiation between defects of Nglycosylation assembly in the ER (type I) and defects of Nglycan trimming and elongation, occurring mainly in the Golgi apparatus (type II). Most recently, wholeexome sequencing has led to the elucidation of the underlying mutation in patients with unknown CDGs. Treatment is available for only three CDG subtypes. In this protocol, we propose to clinically evaluate up to 100 patients of all ethnicities with known or suspected CDGs, obtain cells, plasma, and urine for future studies, perform mutation analysis for known CDGcausing genes, and search for other genes responsible for CDGs. Routine admissions of 35 days will occur annually or as required by changes in clinical symptomatology.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 80 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION/EXCLUSION CRITERIA:

Patients of any gender and ethnicity age 180 years with a suspected CDG based on biochemical tests or a confirmed CDG based on enzymatic or molecular tests will be eligible to enroll in this protocol. Patients will also be excluded if they cannot travel to the NIH due to their medical condition. Infants under age one year or under 10 kg of body weight are excluded because care is more readily provided to older infants at the Clinical Center.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02089789


Contacts
Contact: Lynne A Wolfe, C.R.N.P. (301) 443-8577 wolfela@mail.nih.gov
Contact: Carlos R Ferreira, M.D. (301) 496-9101 ferreiracr@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Investigators
Principal Investigator: Carlos R Ferreira, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Publications:
Responsible Party: National Human Genome Research Institute (NHGRI)
ClinicalTrials.gov Identifier: NCT02089789     History of Changes
Other Study ID Numbers: 140071
14-HG-0071
First Submitted: March 14, 2014
First Posted: March 18, 2014
Last Update Posted: October 19, 2017
Last Verified: August 15, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):
Natural History
Glycosylation
Genetic Disorders

Additional relevant MeSH terms:
Disease
Congenital Disorders of Glycosylation
Pathologic Processes
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases