SLC35C1-CDG (CDG-IIc)

Other Names: CDG 2C; CDG2C; Leukocyte adhesion deficiency type 2; LAD2; Rambam-Hasharon syndrome; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIc; Congenital disorder of glycosylation type IIC

Leukocyte adhesion deficiency type II (LAD-II) is a form of LAD 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.

Cause

LAD-II is a carbohydrate-deficient glycoprotein syndrome (CDG syndrome) 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.

Inheritance

Autosomal recessive inheritance, a 25% chance

Transmission is autosomal recessive manner.

Signs and symptoms

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

1%-4% of people have these symptoms

• Anxiety(Excessive, persistent worry and fear)
• Autism
• Brachydactyly(Short fingers or toes)
• Bronchiolitis
• Coarse facial features(Coarse facial appearance)
• Echolalia(Echoing another person's speech)
• Febrile seizure (within the age range of 3 months to 6 years)(Fever induced seizures)
• Global developmental delay
• Obsessive-compulsive behavior(Obsessive compulsive behavior)
• Recurrent otitis media(Recurrent middle ear infection)
• Short foot(Short feet)
• Short stature(Decreased body height)
• Widow's peak(Hairline peak)

Diagnosis

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.

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.

NIH genetic and rare disease info

• NIH info on SLC35C1-CDG (CDG-IIc)

SLC35C1-CDG (CDG-IIc) is a rare disease.