- For Patients
1. What causes inherited GPI deficiency (IGD)?
All human tissues, such as brain, heart, muscle, and skin, consist of tissue-specific cells, and over 20,000 different proteins are synthesized from genes within those cells. These proteins are localized in organelles, the cytoplasm, and the cell membrane and have many important roles. Among the various proteins on the cell membrane, there is a group of over 150 proteins called GPI-anchored proteins (GPI-APs), which have a common structure; an example of a GPI-AP is alkaline phosphatase (ALP). GPI anchors are glycolipids that anchor these important proteins to the cell membrane; the GPI anchor and the protein with which it associates are separately synthesized, combined, and transported to the cell surface. Twenty-seven genes are known to be necessary for GPI-AP synthesis. A complete defect in one of these genes causes loss of all of these important proteins from the cell surface, leading to embryonic death. IGD is caused by the mutation of these genes, leading to decreased expression of GPI-APs.More detail?
2. What are the symptoms of IGD?
The main symptoms of IGD are intellectual disability, developmental delay, and epilepsy. Although there is a wide range of symptoms depending on the mutated genes and the degree of the defect, tented upper lip, brachytelephalangy with hypoplastic nails, hearing loss, and multiple organ anomalies, such as an aganglionic megacolon, kidney or anorectal anomalies, are characteristic features.
3. Is IGD inherited?
IGD is a hereditary recessive disease caused by a mutation in one of the genes involved in the synthesis of GPI-anchored proteins (GPI-APs). Among these genes, PIGA is X-linked, while all of the others are autosomal genes; therefore, all patients with PIGA deficiency are males who received a mutated PIGA from their mother, while other IGD patients received a mutated gene from each of their parents.
4. How is IGD diagnosed?
Blood samples from patients with epilepsy, developmental delay, or some characteristic features of unknown cause are analyzed by flow cytometry to check the expression level of GPI-anchored proteins (GPI-APs). If their expression is decreased, the patient is diagnosed with IGD. As GPI-APs are expressed normally in some types of IGD, genes in samples from cases suspected of IGD are further analyzed by next-generation sequencing. We analyze blood samples from Japan and are happy to be consulted from abroad. Please ask your doctor to contact us.
5. Are there any effective treatments?
As this is a very recently identified disease and is caused by gene mutations, there is no therapy that can completely cure it. However, as the seizures in IGD are sometimes caused by a lack of vitamin B6 in the neurons because of a defect in uptake due to the decreased surface expression of alkaline phosphatase, pyridoxine (unphosphorylated vitamin B6) treatment is very effective for the seizures in some patients. We consider that early diagnosis and treatment are important and hope to develop new drugs for this condition.