Also known as Leukocyte Adhesion Deficiency Type II (formerly known as CDG IIc)
A rare, inherited condition primarily affecting the immune, endocrine, and nervous systems. It is caused by an abnormal transport protein that disrupts glycosylation. Symptoms manifest in infancy or childhood, including recurrent bacterial infections, the Bombay blood type, short stature, developmental delay, cognitive impairment, behavioral problems, seizures, and hypotonia (low muscle tone).
SLC35C1-CDG is a rare inherited condition that is caused by genetic mutations in the SLC35C1 gene and primarily affects the immune system, the endocrine system and the nervous system. Most patients develop symptoms of the disorder during infancy or childhood.
One of the most common symptoms is a susceptibility for recurrent bacterial infections, including ear infections, sinus infections, pulmonary infections, infections of the skin or the gums, gastroenteritis, or sepsis, which are often associated with an unusually high level of neutrophils in the blood. Often, during these times of fever or infection, no specific pathogens can be identified. Other very typical characteristics in SLC35C1-CDG are short stature, developmental delay (most often affecting speech), cognitive impairment (ranging from mild to severe) and behavioral problems (for example aggressive behavior, anxiety and autism). Features that are present in some, but not all patients with SLC35C1-CDG include feeding problems, seizures and hypotonia (a low muscle tone). Some patients show mildly distinct facial features, which may include an oval face, coarse facial features, a short nose and an underdeveloped nasal bridge. Individual patients have been reported with an abnormally small head (microcephaly), astigmatism (the surface of the eye is curved in an abnormal way) hydronephrosis (swelling of the kidneys due to urine accumulation), hypospadias (the opening of the urethra is on the underside of the penis), atrial septal defect (a hole in the wall that separates the chambers of the heart), celiac disease and delayed appearance of the teeth.
Brain imaging usually does not show any structural abnormalities.
Laboratory investigations typically reveal increased levels of leukocytes (white blood cells), specifically increased neutrophils (a type of white blood cells that plays an important role in fighting off infections), a decreased number of B-lymphocytes, as well as an extremely rare blood group called the “Bombay blood type” (which can lead to autoimmune reactions in case a blood transfusion is necessary due to other reasons). However, these laboratory abnormalities may not be present in mild cases.
There are 14 cases with SLC35C1-CDG that have been reported in medical literature as of 2020.
Patients with SLC35C1-CDG usually have a normal pattern in CDT (carbohydrate deficient transferrin) testing, a screening test for CDG which is widely used to distinguish between different CDG.
Another diagnostic tool for SLC35C1-CDG is the analysis of sugar chains attached to proteins in the blood (serum N-glycans), which can be tested by different methods in blood and fibroblasts. Additionally, there are specific tests that identify specific features of the disease that are caused by the defective glycosylation (H-antigen testing and flow cytometry for CD15).
Genetic testing is needed to confirm the diagnosis. Individuals with SLC35C1-CDG have two faulty copies of the SLC35C1 gene. There is one known mutational variant that has been associated with a rather mild disease course, mainly affecting growth and development, but not leading to significant immunodeficiency. Once molecular testing has confirmed the diagnosis, affected families have the option to pursue genetic counseling.
Treatment and Prognosis
Currently, there are no FDA-approved curative treatments available for SLC35C1-CDG. However, treatment with L-fucose, a special dietary sugar, has been reported to have a positive impact on laboratory abnormalities, infection frequency, growth and psychomotor development (for example speech and attention span) in some cases, particularly those with a mild-immune variant of SLC35C1-CDG. Of note, this treatment has to be medically monitored due to potential side effects but is usually well tolerated. Besides this, most treatment of SLC35C1-CDG is aimed at easing and alleviating the symptoms experienced by the patient (“symptomatic” treatment) and at the prevention of complications. Because SLC35C1-CDG is a disorder that affects many systems in the body, management of SLC35C1-CDG is usually guided by a multidisciplinary medical team.
Long-term prognosis is good and infection frequency tends to decrease after the first years. The oldest individual with SLC35C1-CDG that has been described in medical literature is 22 years old when his case was reported in 2020.