PIGT
Name of disorder PIGT-congenital disorder of glycosylation (PIGT-CDG, also known as phosphatidylinositol-glycan class T protein deficiency or Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 3). It belongs to a group of disorders called Glycosylphosphatidylinositol (GPI-) anchor defects.
Symptoms

PIGT-CDG is a very rare inherited condition that affects multiple parts of the body and causes multiple congenital anomalies. Affected individuals typically develop signs and symptoms of the condition during infancy. PIGT-CDG presents with a primarily neurologic phenotype: Frequent and characteristic symptoms are muscle hypotonia, severe global developmental delay, intellectual disability and epilepsy (with seizure onset between the first days of life to a few years of age). In some patients, seizures are treatable with antiepileptic medication, but in many, epilepsy is difficult to treat and some patients have severe neonatal onset epileptic encephalopathy. The patients show mild, but relatively distinct abnormal facial features (high forehead, bitemporal narrowing, depressed nasal bridge, long philtrum) and macrocephaly. Other frequent features include skeletal abnormalities, joint hypermobility, renal and ophthalmological features. Some patients have been described with cardiac abnormalities, pulmonary symptoms, intestinal malformations or hearing loss.

Frequent laboratory findings are low concentrations of alkaline phosphatase in the blood, hypercalcemia, hypercalciuria and suppressed (low) levels of parathyroid hormone.

Brain imaging often shows abnormalities, but can also be normal.

There are 25 individuals with PIGT-CDG published in the medical literature.

Diagnosis

The primary screening tool for PIGT-CDG is testing for the presence of GPI-anchored proteins on the surface of granulocytes (a subset of white blood cells). This can be tested by a method called flow cytometry in the patient’s blood. The ultimate diagnosis is genetic testing in blood. Individuals with PIGT-CDG have two faulty copies of the PIGT gene.

Treatment and prognosis

To date, there are no known specific treatment options for PIGT-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. Most diagnosed PIGT-CDG patients are still young, which makes long-term prognosis difficult. The oldest individual with PIGT-CDG that has been described in the medical literature is almost 30 years old.