National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

SLC35C1-CDG (CDG-IIc)


Other Names:
CDG 2C; CDG2C; Leukocyte adhesion deficiency type 2; CDG 2C; CDG2C; Leukocyte adhesion deficiency type 2; LAD2; Rambam-Hasharon syndrome; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIc; Congenital disorder of glycosylation type IIC See More
Categories:
This disease is grouped under:
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 99843

Definition
Leukocyte adhesion deficiency type II (LAD-II) is a form of LAD (see this term) characterized by recurrent bacterial infections, severe growth delay and severe intellectual deficit.

Epidemiology
LAD-II is extremely rare: less than 10 cases have been reported so far.

Clinical description
The first signs usually occur in infancy or early childhood. Patients present recurrent bacterial infections, severe growth delay resulting in short stature, and severe intellectual deficit. Patients have the Bombay phenotype (they do not express the H antigen). Facial dysmorphism is common, characterized mainly by a depressed nasal bridge. Severe periodontitis is often present later in life and leads to early tooth loss. In adulthood, intellectual deficit and growth retardation, rather than infections, dominate the clinical picture.

Etiology
LAD-II is a carbohydrate-deficient glycoprotein syndrome (CDG syndrome; see this term) and is therefore also referred to as CDG IIc. It results from mutations in the SLC35C1 gene (11p11.2), encoding the guanosine 5'-diphosphate (GDP)-fucose transporter localized in the Golgi apparatus. This is a specific fucose transporter that translocates GDP-fucose from the cytosol to the Golgi where it is used as a substrate for fucosylation.

Diagnostic methods
Diagnosis is based on clinical findings and complete blood counts revealing leukocytosis with neutrophilia. Blood typing is essential to look for the Bombay blood group, which is present in all patients with LAD-II and is extremely rare in the general population. Final diagnosis is based on genetic analysis.

Differential diagnosis
There is no differential diagnosis as the clinical symptoms of recurrent infections, leukocytosis, the Bombay blood group, and severe growth and intellectual deficit are unique to LAD-II.

Antenatal diagnosis
Antenatal diagnosis through biochemical or molecular analysis of chorionic villus cells or amniocytes is possible in families for which the mutation has been identified.

Genetic counseling
Transmission is autosomal recessive.

Management and treatment
Management should focus on controlling infections and includes antibiotics. Fucose replacement may improve phagocytic function in some cases.

Prognosis
Infections in LAD-II are rarely life-threatening and thus patients may live to adulthood.

Visit the Orphanet disease page for more resources.
Last updated: 5/1/2009

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 28 |
Medical Terms Other Names
Learn More:
HPO ID
1%-4% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
Autism 0000717
Brachydactyly
Short fingers or toes
0001156
Bronchiolitis 0011950
Coarse facial features
Coarse facial appearance
0000280
Echolalia
Echoing another person's speech
0010529
Febrile seizure (within the age range of 3 months to 6 years)
Fever induced seizures
0002373
Global developmental delay 0001263
Obsessive-compulsive behavior
Obsessive compulsive behavior
0000722
Recurrent otitis media
Recurrent middle ear infection
0000403
Short foot
Short feet
Small feet
[ more ] 		0001773
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Widow's peak
Hairline peak
Hairline point
Pointed hairline at front of head
V-shaped frontal hairline
[ more ] 		0000349
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality
[ more ] 		0001939
Abnormality of the integument 0001574
Autosomal recessive inheritance 0000007
Bulbous nose 0000414
Cellulitis
Bacterial infection of skin
Skin infection
[ more ] 		0100658
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation
[ more ] 		0006887
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation
[ more ] 		0010864
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Muscular hypotonia
Low or weak muscle tone
0001252
Neutrophilia
Increased blood neutrophil counts
0011897
Periodontitis 0000704
Pneumonia 0002090
Reduction of neutrophil motility 0005400
Showing of 28 |
Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

  • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss SLC35C1-CDG (CDG-IIc). Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.