Also known as congenital disorder of glycosylation type Ib
A rare, inherited condition caused by abnormal proteins disrupting N-linked glycosylation and mainly affecting the liver and intestinal system. Symptoms manifest during infancy, including cyclic vomiting, failure to thrive, hypoglycemia, hypoalbuminemia, coagulopathy, liver fibrosis (formation of scar tissue) or steatosis (buildup of fat), hepatomegaly (enlarged liver), and, rarely, portal hypertension.
Symptoms
MPI-CDG is a treatable, inherited condition that mainly affects the liver and the intestinal system. Individuals with MPI-CDG typically develop signs and symptoms of the condition during infancy. Affected infants may have early symptoms of hypoglycemia, gastrointestinal, and liver involvement (and can develop fibrosis or steatosis), with hepatomegaly being the most common clinical sign. In contrast to other forms of CDG, patients with MPI-CDG usually do not present with dysmorphic features, intellectual disability or neurological involvement. Feeding difficulties, recurrent vomiting, chronic diarrhea and protein-losing enteropathy can lead to a failure to gain weight, and patients often grow slower than normal (failure to thrive). Hypoalbuminemia is present in most of the cases as a result of exudative enteropathy and can lead to peripheral edema. Recurrent thromboses and GI-bleeding due to sever coagulation abnormalities can lead to life-threatening episodes in the first months of life. During adolescence or adulthood, individuals with MPI-CDG might develop thromboses (blood clots in the deep veins). A rare, but serious complication in adulthood, resulting from progressive liver fibrosis and cirrhosis, is portal hypertension with esophageal varices and hepatopulmonary syndrome.
Elevated liver enzymes are common in MPI-CDG. Transaminases are usually only slightly elevated, with GGT and bilirubin often resulting as normal. Abnormal coagulation factor activities are frequent findings. They are mainly due to the glycosylation abnormalities but can be exacerbated by protein-losing enteropathy and liver failure, if present. Hypoglycemia is most often due to hyperinsulinism, but insulin can be normal in some cases.
There are more than 35 MPI-CDG patients published in medical literature.
Diagnosis
Early diagnosis is crucial in MPI-CDG as it is a potentially life-threatening, but treatable disease. 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. Measuring the activity of the deficient enzyme, MPI, in blood and skin fibroblasts confirms the diagnosis. The ultimate diagnosis is genetic testing in blood. Individuals with MPI-CDG have two faulty copies of the MPI gene.
Treatment and Prognosis
MPI-CDG has been the first CDG treatable by dietary therapy. Oral mannose supplementation is effective in improving hypoglycemia, coagulopathy and hypoalbuminemia, leading to an improvement of the patient’s overall condition and digestive symptoms within a few weeks. However, liver involvement can be progressive and irreversible. Liver transplantation may be necessary in select cases to prevent further loss of liver function and progressive fibrosis (possibly leading to cirrhosis). With the available therapeutic options, MPI-CDG patients seem to have a good life expectancy. The oldest MPI-CDG patient is in her late 30s.