Also known as phosphatidylinositol-glycan class A protein deficiency; multiple congenital anomalies-hypotonia-seizures syndrome 2
A rare, X-linked, glycosylphosphatidylinositol anchor defect disorder, caused by an abnormal enzyme disrupting glycosylation. Symptoms include global developmental delay, seizures, hypo/hypertonia, dystonia, cortical visual impairment, slow gastrointestinal motility, delayed myelination, and problems with sleep, respiration, and swallowing.
Symptoms
PIGA-CDG is an extremely rare genetic disorder impacting children from birth. The symptoms of PIGA-CDG are wide-ranging in both scope and severity. Not all children with PIGA-CDG may exhibit all symptoms and some children will exhibit additional symptoms. Children with PIGA-CDG often have global developmental delays, seizures (e.g., infantile spasms, myoclonic), respiratory complications, muscle tone abnormalities (hypotonia, hypertonia, dystonia), cortical visual impairment (CVI), gastrointestinal issues (e.g., slow motility), sleep disorders, difficulty swallowing leading to aspiration, delayed myelination (which can be seen on MRIs). There are close to 100 individuals with PIGA-CDG published in medical literature.
Diagnosis
PIGA-CDG is usually diagnosed through genetic blood tests, either as part of an epilepsy panel or through whole exome sequencing. PIGA-CDG can also be identified by 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.
Patients have been found all over the world, so the mutation does not appear to be concentrated in any given area or confined to certain ethnicities. However, only males have been found to show symptoms of the PIGA mutation because the mutation is X-linked (located on the X chromosome).
Treatment and Prognosis
To date, there are no known specific treatment options for PIGA-CDG, though a PIGA-CDG gene therapy treatment is currently under investigation in early pre-clinical research studies. Most current treatments are aimed at symptom management. 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. Moreover, many children with PIGA-CDG end up requiring a feeding tube to help reduce the chance of aspiration due to swallowing issues and muscle tone abnormalities. Those diagnosed with PIGA-CDG often have a lower life expectancy, with many patients passing away early in life due to respiratory complications brought on by the mutation.