Also known as Congenital Disorder of Glycosylation Type IIu; Rafiq Syndrome; MAN1B1 Deficiency; Intellectual Disability-Truncal Obesity Syndrome
A rare, inherited condition, primarily affecting the central nervous system, caused by an abnormal protein disrupting N-linked glycosylation. Symptoms manifest during infancy, including intellectual and developmental disabilities, hypotonia (low muscle tone), speech problems, truncal obesity, and facial dysmorphism (abnormal difference in structure). Some individuals have skin laxity, joint hypermobility, and behavioral problems.
Individuals with MAN1B1-CDG typically develop signs and symptoms of the condition during infancy. MAN1B1-CDG patients exhibit mild-severe intellectual and developmental disability. Most patients also show decreased muscle tone (hypotonia), abnormal speech development, delayed motor skills, abnormalities of facial features (facial dysmorphism), and excessive fat around the stomach area (truncal obesity). Abnormal facial features include a large head (macrocephaly), a flat oval face, down-slanting palpebral fissures, prominent eyebrows with lateral thinning, strabismus, large ears, a prominent bulbous nose tip and a tent-shaped mouth with a thin upper lip. Other symptoms reported in only some patients with MAN1B1-CDG include a long head (dolichocephaly), loose skin (skin laxity), flexible joints (joint hyperlaxity), and long and thin fingers (arachnodactyly). A subset of patients with MAN1B1-CDG have been observed to show behavioral problems such as aggression and overeating. Laboratory abnormalities for MAN1B1-CDG patients include abnormal coagulation tests and elevation of liver enzymes (serum transaminases). The age of patients with MAN1B1-CDG can influence which type of symptoms are present. Although MAN1B1-CDG patients show different symptoms across the body, the main features of this disorder involve the central nervous system. There are more than 42 MAN1B1-CDG patients published in the medical literature.
The primary screening tool is testing of the appropriate glycosylation of common proteins (one commonly used glycoprotein is transferrin). This can be tested by different methods in blood. The diagnosis is confirmed by genetic testing in blood. Individuals with MAN1B1-CDG have two faulty copies of the MAN1B1 gene.
Treatment and Prognosis
Currently, there are no curative treatments available for MAN1B1-CDG. Therefore, treatment of MAN1B1-CDG is aimed at easing and alleviating the symptoms experienced by the patient (symptomatic treatment). Because MAN1B1-CDG is a disorder that affects many systems in the body simultaneously, management of MAN1B1-CDG is usually guided by a multidisciplinary medical team.