Rare Neurology News

Disease Profile

SLC35C1-CDG (CDG-IIc)

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

D84.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

CDG 2C; CDG2C; Leukocyte adhesion deficiency type 2;

Categories

Congenital and Genetic Diseases; Immune System Diseases; Metabolic disorders;

Summary

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.

Symptoms

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.

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Diagnosis

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.

    Organizations

    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).

        Learn more

        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.

            Rare Neurology News

            Medical Terms Other Names
            Learn More:
            HPO ID
            80%-99% of people have these symptoms
            Abnormal isohemagglutinin level
            Abnormal level of natural antibody to blood group agents
            Abnormal natural antibody level to blood group antigens in blood (isohemagglutinin)

            [ more ]

            0410292
            Coarse facial features
            Coarse facial appearance
            0000280
            Failure to thrive
            Faltering weight
            Weight faltering

            [ more ]

            0001508
            Leukocytosis
            Elevated white blood count
            High white blood count
            Increased blood leukocyte number

            [ more ]

            0001974
            Neutrophilia
            Increased blood neutrophil counts
            0011897
            Short stature
            Decreased body height
            Small stature

            [ more ]

            0004322
            30%-79% of people have these symptoms
            Autistic behavior
            0000729
            Cerebral atrophy
            Degeneration of cerebrum
            0002059
            Intellectual disability, severe
            Early and severe mental retardation
            Mental retardation, severe
            Severe mental retardation

            [ more ]

            0010864
            Intrauterine growth retardation
            Prenatal growth deficiency
            Prenatal growth retardation

            [ more ]

            0001511
            Microcytic anemia
            0001935
            Recurrent fever
            Episodic fever
            Increased body temperature, episodic
            Intermittent fever

            [ more ]

            0001954
            Seizure
            0001250
            Sleep disturbance
            Difficulty sleeping
            Trouble sleeping

            [ more ]

            0002360
            Small for gestational age
            Birth weight less than 10th percentile
            Low birth weight

            [ more ]

            0001518
            5%-29% of people have these symptoms
            Ataxia
            0001251
            Broad eyebrow
            Broad eyebrows
            Flared eyebrow
            Increased vertical height of eyebrow
            Increased vertical thickness of eyebrow

            [ more ]

            0011229
            Broad palm
            Broad hand
            Broad hands
            Wide palm

            [ more ]

            0001169
            Chronic diarrhea
            0002028
            Chronic lymphocytic meningitis
            0007041
            Conductive hearing impairment
            Conductive deafness
            Conductive hearing loss

            [ more ]

            0000405
            Deep philtrum
            0002002
            Depressed nasal bridge
            Depressed bridge of nose
            Flat bridge of nose
            Flat nasal bridge
            Flat, nasal bridge
            Flattened nasal bridge
            Low nasal bridge
            Low nasal root

            [ more ]

            0005280
            Depressed nasal ridge
            Flat nose
            Recessed nasal ridge

            [ more ]

            0000457
            Esodeviation
            0020045
            Generalized hypotonia
            Decreased muscle tone
            Low muscle tone

            [ more ]

            0001290
            Gingival overgrowth
            Gum enlargement
            0000212
            Hepatomegaly
            Enlarged liver
            0002240
            Hyperreflexia
            Increased reflexes
            0001347
            Hypertelorism
            Wide-set eyes
            Widely spaced eyes

            [ more ]

            0000316
            Hypoplasia of the frontal lobes
            Underdeveloped frontal lobe
            0007333
            Impaired tandem gait
            Clumsy tandem walking
            0031629
            Keratitis
            Corneal inflammation
            0000491
            Limb undergrowth
            limb shortening
            Short limb
            Short limbs

            [ more ]

            0009826
            Long eyelashes
            Increased length of eyelashes
            Unusually long eyelashes

            [ more ]

            0000527
            Long upper lip
            Elongation of upper lip
            Increased height of upper lip
            Increased vertical length of upper lip

            [ more ]

            0011341
            Low anterior hairline
            Low frontal hairline
            Low-set frontal hairline

            [ more ]

            0000294
            Lower limb hypertonia
            0006895
            Mandibular prognathia
            Big lower jaw
            Increased projection of lower jaw
            Increased size of lower jaw
            Large lower jaw
            Prominent chin
            Prominent lower jaw

            [ more ]

            0000303
            Microcephaly
            Abnormally small skull
            Decreased circumference of cranium
            Decreased size of skull
            Reduced head circumference
            Small head circumference

            [ more ]

            0000252
            Microtia
            Small ears
            Underdeveloped ears

            [ more ]

            0008551
            Narrow palate
            Narrow roof of mouth
            0000189
            Overlapping toe
            Overlapping toes
            Overriding toes

            [ more ]

            0001845
            Palpebral edema
            Fullness of eyelids
            Puffy eyelids
            Puffy lids
            Swelling of eyelids

            [ more ]

            0100540
            Premature loss of teeth
            Early tooth loss
            Loss of teeth
            Premature teeth loss
            Premature tooth loss

            [ more ]

            0006480
            Protruding tongue
            Prominent tongue
            Tongue sticking out of mouth

            [ more ]

            0010808
            Recurrent gastroenteritis
            0031123
            Recurrent otitis media
            Recurrent middle ear infection
            0000403
            Recurrent pneumonia
            0006532
            Recurrent urinary tract infections
            Frequent urinary tract infections
            Repeated bladder infections
            Repeated urinary tract infections
            Urinary tract infections
            Urinary tract infections, recurrent

            [ more ]

            0000010
            Scarring
            0100699
            Severe periodontitis
            0000166