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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation

Brief Summary:

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
  

  Detailed Summary: 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 u
  Sponsor: National Human Genome Research Institute (NHGRI)
  

  Current Primary Outcome: 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 ]
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome:
  
  

  Original Secondary Outcome:
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: March 14, 2014
  Date Started: March 6, 2014
  Date Completion: December 1, 2018
  Last Updated: April 20, 2017
  Last Verified: January 18, 2017