Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 1 - 80 |
| Updated: | 1/20/2019 |
| Start Date: | March 7, 2014 |
| End Date: | December 1, 2023 |
| Contact: | Lynne A Wolfe, C.R.N.P. |
| Email: | wolfela@mail.nih.gov |
| Phone: | (301) 443-8577 |
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.
- 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.
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 3-5 days will occur annually or
as required by changes in clinical symptomatology.
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 3-5 days will occur annually or
as required by changes in clinical symptomatology.
- 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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