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Glucose phosphate isomerase deficiency

(often shortened to GPI deficiency)
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.

Related Gene(s)

Changes in this gene are associated with glucose phosphate isomerase deficiency.

  • GPI

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.

  • Genetic Testing Registry: Glucosephosphate isomerase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN072763)
  • Genetic Testing Registry: Hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150730)
  • National Heart, Lung, and Blood Institute: How is Hemolytic Anemia Diagnosed? (http://www.nhlbi.nih.gov/health/health-topics/topics/ha/diagnosis)
  • National Heart, Lung, and Blood Institute: How is Hemolytic Anemia Treated? (http://www.nhlbi.nih.gov/health/health-topics/topics/ha/treatment)

You might also find information on the diagnosis or management of GPI deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/glucose-phosphate-isomerase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/glucose-phosphate-isomerase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) 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?

  • glucose-6-phosphate isomerase deficiency
  • glucosephosphate isomerase deficiency
  • nonspherocytic hemolytic anemia due to glucose phosphate isomerase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about GPI deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding GPI deficiency?

anemia ; ataxia ; autosomal ; autosomal recessive ; bile ; cell ; chronic ; deficiency ; disability ; dyspnea ; enlarged spleen ; enzyme ; fructose ; gallbladder ; gene ; glucose ; hemolysis ; hemolytic anemia ; inherited ; iron ; jaundice ; molecule ; monomer ; 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 (http://www.ghr.nlm.nih.gov/glossary).

References

  • Baronciani L, Zanella A, Bianchi P, Zappa M, Alfinito F, Iolascon A, Tannoia N, Beutler E, Sirchia G. Study of the molecular defects in glucose phosphate isomerase-deficient patients affected by chronic hemolytic anemia. Blood. 1996 Sep 15;88(6):2306-10. (http://www.ncbi.nlm.nih.gov/pubmed/8822952?dopt=Abstract)
  • Beutler E, West C, Britton HA, Harris J, Forman L. Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA). Blood Cells Mol Dis. 1997 Dec;23(3):402-9. (http://www.ncbi.nlm.nih.gov/pubmed/9446754?dopt=Abstract)
  • Fujii H, Kanno H, Hirono A, Miwa S. Hematologically important mutations: molecular abnormalities of glucose phosphate isomerase deficiency. Blood Cells Mol Dis. 1996;22(2):96-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/8931949?dopt=Abstract)
  • Kanno H, Fujii H, Hirono A, Ishida Y, Ohga S, Fukumoto Y, Matsuzawa K, Ogawa S, Miwa S. Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia. Blood. 1996 Sep 15;88(6):2321-5. (http://www.ncbi.nlm.nih.gov/pubmed/8822954?dopt=Abstract)
  • Kugler W, Breme K, Laspe P, Muirhead H, Davies C, Winkler H, Schröter W, Lakomek M. Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency. Hum Genet. 1998 Oct;103(4):450-4. (http://www.ncbi.nlm.nih.gov/pubmed/9856489?dopt=Abstract)
  • Lakomek M, Winkler H. Erythrocyte pyruvate kinase- and glucose phosphate isomerase deficiency: perturbation of glycolysis by structural defects and functional alterations of defective enzymes and its relation to the clinical severity of chronic hemolytic anemia. Biophys Chem. 1997 Jun 30;66(2-3):269-84. (http://www.ncbi.nlm.nih.gov/pubmed/9362562?dopt=Abstract)
  • Repiso A, Oliva B, Vives-Corrons JL, Beutler E, Carreras J, Climent F. Red cell glucose phosphate isomerase (GPI): a molecular study of three novel mutations associated with hereditary nonspherocytic hemolytic anemia. Hum Mutat. 2006 Nov;27(11):1159. (http://www.ncbi.nlm.nih.gov/pubmed/17041899?dopt=Abstract)
  • Warang P, Kedar P, Ghosh K, Colah RB. Hereditary non-spherocytic hemolytic anemia and severe glucose phosphate isomerase deficiency in an Indian patient homozygous for the L487F mutation in the human GPI gene. Int J Hematol. 2012 Aug;96(2):263-7. doi: 10.1007/s12185-012-1122-x. Epub 2012 Jul 11. (http://www.ncbi.nlm.nih.gov/pubmed/22782259?dopt=Abstract)
  • Xu W, Beutler E. The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia. J Clin Invest. 1994 Dec;94(6):2326-9. (http://www.ncbi.nlm.nih.gov/pubmed/7989588?dopt=Abstract)

 

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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2013
Published: December 22, 2014