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Glucose phosphate isomerase deficiency
(often shortened to GPI deficiency)
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Reviewed December 2013
What is GPI deficiency?
Glucose phosphate isomerase (GPI) deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), extreme tiredness (fatigue), shortness of breath (dyspnea), and a rapid heart rate (tachycardia). An enlarged spleen (splenomegaly), an excess of iron in the blood, and small pebble-like deposits in the gallbladder or bile ducts (gallstones) may also occur in this disorder.
Hemolytic anemia in GPI deficiency can range from mild to severe. In the most severe cases, affected individuals do not survive to birth. Individuals with milder disease can survive into adulthood. People with any level of severity of the disorder can have episodes of more severe hemolysis, called hemolytic crises, which can be triggered by bacterial or viral infections.
A small percentage of individuals with GPI deficiency also have neurological problems, including intellectual disability and difficulty with coordinating movements (ataxia).
How common is GPI deficiency?
GPI deficiency is a rare cause of hemolytic anemia; its prevalence is unknown. About 50 cases have been described in the medical literature.
What genes are related to GPI deficiency?
GPI deficiency is caused by mutations in the GPI gene, which provides instructions for making an enzyme called glucose phosphate isomerase (GPI). This enzyme has two distinct functions based on its structure. When two GPI molecules form a complex (a homodimer), the enzyme plays a role in a critical energy-producing process known as glycolysis, also called the glycolytic pathway. During glycolysis, the simple sugar glucose is broken down to produce energy. Specifically, GPI is involved in the second step of the glycolytic pathway; in this step, a molecule called glucose-6-phosphate is converted to another molecule called fructose-6-phosphate.
When GPI remains a single molecule (a monomer) it is involved in the development and maintenance of nerve cells (neurons). In this context, it is often known as neuroleukin (NLK).
Some GPI gene mutations may result in a less stable homodimer, impairing the activity of the enzyme in the glycolytic pathway. The resulting imbalance of molecules involved in the glycolytic pathway eventually impairs the ability of red blood cells to maintain their structure, leading to hemolysis.
Other GPI gene mutations may cause the monomer to break down more easily, thereby interfering with its function in nerve cells. In addition, the shortage of monomers hinders homodimer formation, which impairs the glycolytic pathway. These mutations have been identified in individuals with GPI deficiency who have both hemolytic anemia and neurological problems.
Read more about the GPI gene.
How do people inherit GPI deficiency?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Where can I find information about diagnosis or management of GPI deficiency?
These resources address the diagnosis or management of GPI deficiency and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about GPI deficiency?
You may find the following resources about GPI deficiency helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for GPI deficiency?
What if I still have specific questions about GPI deficiency?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding GPI deficiency?
anemia ; ataxia ; autosomal ; autosomal recessive ; bile ; cell ; chronic ; deficiency ; dyspnea ; enlarged spleen ; enzyme ; gallbladder ; gene ; glucose ; hemolysis ; hemolytic anemia ; iron ; jaundice ; molecule ; neurological ; oxygen ; pallor ; phosphate ; prevalence ; recessive ; simple sugar ; splenomegaly ; tachycardia
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (9 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.