PEPCK Deficiency

PEPCK Deficiency

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report PEPCK Deficiency is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Phosphoenolpyruvate Carboxykinase Deficiency

Disorder Subdivisions

  • PEPCK Cytosolic
  • PEPCK Mitochondrial

General Discussion

PEPCK deficiency is an extremely rare disorder of carbohydrate metabolism inherited as an autosomal recessive trait. A deficiency of the enzyme phosphoenolpyruvate carboxykinase (PEPCK), which is a key enzyme in the conversion of proteins and fat to glucose (gluconeogenesis), causes an excess of acid in the circulating blood (acidemia). Characteristics of this disorder are low blood sugar (hypoglycemia), loss of muscle tone, liver enlargement and impairment, and failure to gain weight and grow normally.

Symptoms

There are two forms of PEPCK deficiency: cytosolic and mitochondrial. Both forms represent an inherited deficiency in the enzyme phosphoenolpyruvate carboxykinase. This enzyme is key in the process of converting proteins and fat to glucose (gluconeogenesis).



Symptoms of this disorder include the presence of excess acid in the circulating blood (lactic acidemia); loss of muscle tone (hypotonia); abnormal enlargement of the liver (hepatomegaly); inability to gain appropriate weight and grow normally (failure to thrive); and an abnormally low blood sugar (glucose) level (hypoglycemia). Glucose is essential as the body's source of energy, and for the functioning of many organs and systems in the body, especially the central nervous system.



At or shortly after birth, the infant with PEPCK deficiency may have an enlarged liver, apnea, and a moderate delay in motor functions. Poor appetite, vomiting, coma, convulsions, and seizures may be present. Liver impairment produces increased liver enzymes, alanine, glycine, and glutamine levels. At least one case reported to date has involved atrophy of the optic nerve.



The course of this disorder can be very rapid.

Causes

PEPCK deficiencies, in both forms, are very rare disorders that are inherited as autosomal recessive traits. The abnormal gene that is responsible for the cytosolic (soluble) form of PEPCK deficiency has been traced to gene map locus 20q13.31.



Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 20q13.31" refers to band 13.31 on the long arm of chromosome 20. The numbered bands specify the location of the thousands of genes that are present on each chromosome.



Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.



Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.



All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

PEPCK deficiency is extremely rare. One overview suggests that only 10 cases have been reported in the medical literature.

Standard Therapies

Diagnosis

Diagnosis of PEPCK deficiency can be made shortly after birth by biochemical analysis of fibroblast cells.



Treatment

Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Sutyherland C. PEPCK Deficiency. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:486.



Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:182.



Scriver CR, Beaudet AL, Sly WS, et al., eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:2288; 2290.



Clarke JTR. A Clinical Guide to Inherited Metabolic Diseases. 1st ed. Cambridge University Press, Cambridge, UK; 1996:108.



JOURNAL ARTICLES

Van den Berghe G. Disorders of gluconeogenesis. J Inher Metab Dis. 1996;19:470-77.



Modaressi S. Christ B. Bratke J, Zahn S, Heise T, Jungermann K. Molecular cloning, sequencing and expression of the cDNA of the mitochondrial form of phosphoenolpyruvate carboxykinase from human liver. Biochem J. 1996;315:807-14.



Leonard JV, Hyland K, Furukawa N, Clayton PT. Mitochondrial phosphoenolpyruvate carboxykinase deficiency. Eur J Pediatr. 1991;150:198-99.



Cao H, van der Veer, Ban MR, Hanley AJG, et al. Promoter polymorphism in PCK1 (phosphoenolpyruvate carboxykinase gene) associated with type 2 diabetes mellitus. J Clin Endocr Metab. 2004;89:898-903.



Yu H, Thun R, Chandrasekharappa S, Trent JM, Zhang J, Meisler MH. Human PCK1 encoding phosphoenolpyruvate carboxykinase is located on chromosome 20q13.2. Genomics. 1993;15:219-21.



Vidnes J, Sovik O. Gluconeogenesis in infancy and childhood. III. Deficiency of the extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hyperglycaemia. Acta Paediatr Scand. 1976;15:219-21.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Phosphoenolpyruvate Carboxykinase 1, Soluble; PCK1. Entry Number; 261-680: Last Edit Date; 4/12/2005.



McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Phosphoenolpyruvate Carboxykinase 2, Mitochondrial; PCK2. Entry Number; 261650: Last Edit Date;7/13/2004.



Phosphoenolpyruvate carboxykinase (PEPCK) deficiency. Orphanet. Update 20/08/2006. 1p.

http://www.orpha.net//consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2880



King MW. Gluconeogenesis. Indiana State University. Last modified: 22-Mar-2006. 9pp.

http://web.indstate.edu/thcme/mwking/gluconeogenesis.html

Resources

CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk



United Mitochondrial Disease Foundation

8085 Saltsburg Road Suite 201

Pittsburgh, PA 15239

United States

Tel: (412)793-8077

Fax: (412)793-6477

Tel: (888)317-8633

Email: info@umdf.org

Internet: http://www.umdf.org



Lactic Acidosis Support Trust

1A Whitley Close

Middlewich

Cheshire, CW10 0NQ

United Kingdom

Tel: 0160683719

Fax: 01606837198



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



MitoAction

14 Pembroke Street

Medford, MA 02155

Tel: (888)648-6228

Fax: (888)648-6228

Email: info@mitoaction.org

Internet: http://www.MitoAction.org



Childhood Liver Disease Research and Education Network

c/o Joan M. Hines, Research Administrator

Children's Hospital Colorado

13123 E 16th Ave. B290

Aurora, CO 80045

Tel: (720)777-2598

Fax: (720)777-7351

Email: joan.hines@childrenscolorado.org

Internet: http://www.childrennetwork.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.