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GMPPA-Congenital Disorder of Glycosylation

A rare inherited condition caused by defective regulation of GMPPB, which leads to a deficiency in the production of an essential sugar molecule (GDP-Mannose). Symptoms manifest at birth or during infancy and include lack of tears (alacrima), difficulty in swallowing due to problems in the esophagus muscle (achalasia), and intellectual disability.

Symptoms

GMPPA-CDG is a very rare condition which affects different parts of the body. Almost all patients exhibit the classic triad of achalasia, alacrima and intellectual disability. Short stature, facial dysmorphisms, hypotonia (decreased muscle tone) and ocular symptoms are also frequently observed. Gait abnormalities, seizures and hearing impairment have been reported although with much lesser frequency.

Individuals with GMPPA-CDG typically develop their first signs and symptoms of the condition at birth. The swallowing difficulties can lead to vomiting, dental caries, and weight loss. There are no specific laboratory abnormalities or brain imaging abnormalities associated with GMPPA-CDG. Hearing and visual impairment should be assessed in children with GMPPA-CDG.

Diagnosis

The ultimate diagnosis is made by using genetic testing in blood. Individuals with GMPPA-CDG have two faulty copies of the GMPPA gene.

Treatment and Prognosis

To date, there are no known specific treatment options for GMPPA-CDG. Treatment is directed to the symptoms and may involve using artificial tears, medication, balloon dilation or surgery to correct the swallowing difficulties, and physical therapy. GMPPA-CDG is not lethal and all patients reach adulthood.