What is PIGA-CDG?
PIGA-CDG is an extremely rare genetic disorder impacting children from birth. It is also referred to as PIGA deficiency or Multiple Congenital Anomalies-Hypotonia-Seizures syndrome type 2 (MCAHS2).
What does the PIGA gene do in the body?
The PIGA gene encodes for a protein that is part of the enzyme complex that catalyzes the first step of the GPI-anchor synthesis process. These GPI-anchor proteins are vital to the proper development and function of many organs within the body, which is why PIGA mutations can result in a variety of severe symptoms.
What type of disorder is PIGA-CDG?
The PIGA gene falls under a group of rare inherited metabolic diseases called Congenital Disorders of Glycosylation (CDG) because the gene is involved in the glycosylation process. The process of glycosylation is critical to normal organ development throughout the body. It seems especially critical for the development and maturation of the nervous system. More information about CDGs can be found at http://cdgcare.com/what-is-cdg/.
Within the CDG group, PIGA-CDG falls under the GPI-anchor pathway. The GPI-anchor pathway is one of eight glycosylation pathways that exist; CDGs have been found in seven of them.
GPI-anchor CDGs
The following image shows the genes within the GPI-anchor pathway that have been associated with known CDGs.
GPI-Anchor Pathway
The following image shows the steps involved in the GPI-anchor pathway and the genes involved in each step.
How is PIGA-CDG diagnosed?
PIGA-CDG is usually diagnosed through whole exome sequencing. Because the disorder is so rare, it is difficult to diagnosis through more common means. While whole exome sequencing is becoming more widespread, many insurance companies still don’t cover it, meaning many rare diseases are likely still being underreported.
How many people have PIGA-CDG?
As of 2020, we’re aware of ~100 individuals ever found to have a PIGA mutation, many of whom passed at a very young age due to aspiration pneumonia. It is one of the more common GPI-anchor genetic mutations. As access to whole exome sequencing improves, the number of impacted individuals will likely increase.
Are certain races, genders or countries more impacted by PIGA-CDG?
Patients have been found all over the world, so the mutation does not appear to be concentrated in any given area. However, only males have been found to show symptoms of the PIGA mutation because the mutation is X-linked (located on the X chromosome).
Females have two X chromosomes, so an impacted girl will typically just be a carrier, and her other X will play a more prominent role. Males have only one X chromosome to go with one Y chromosome. So if a boy has a PIGA mutation in his X chromosome, he will likely show some of the common PIGA-CDG symptoms.
How can I get connected to other PIGA-CDG or CDG families?
This page lists key Facebook groups that will help you get in touch with other families affected by PIGA-CDG or similar disorders.