Hyperprolinemia Type II

Hyperprolinemia Type II

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Hyperprolinemia Type II 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

  • Pyrroline Carboxylate Dehydrogenase Deficiency

Disorder Subdivisions

  • None

General Discussion

Two types of hyperprolinemia are recognized by physicians and clinical researchers. Each represents an inherited inborn error of metabolism involving the amino acid, proline.



Hyperprolinemia Type I (HP-I) is characterized by high levels of proline in the blood resulting from a deficiency of the enzyme proline oxidase, which is key to the breakdown (metabolism) of proline. There are often no clinical manifestations of HP-1.



Hyperprolinemia II (HP-II) is a rare metabolic disorder that results from the deficiency of the enzyme known as delta-pyrroline-5-carboxylate (P-5-C) dehydrogenase. This disorder results in more severe clinical manifestations than are seen in HP-I, and may be associated with mild mental retardation and seizures.

Symptoms

Hyperprolinemia Type II is characterized by an abnormally high level of the amino acid proline in the blood. Fevers associated with seizures are common and mild mental retardation may be present.

Causes

Hyperprolinemia Type II is an autosomal recessive disorder. The gene involved has been mapped to the short arm of chromosome 1 (1p36). Chromosomes, which are present in the nucleus of human cells, carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q". Chromosomes are further subdivided into many bands that are numbered. For example, chromosome 1p36 refers to band 36 on the short arm of chromosome 1.



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 4 to 5 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 of having children with a recessive genetic disorder.

Affected Populations

Hyperprolinemia Type II is a very rare disorder that is present at birth. It affects males and females in equal numbers.

Standard Therapies

Diagnosis

HP-II is recognized by elevated blood proline and elevated P-5-C levels in the urine. (Normal blood proline levels are about 450 units whereas elevated blood proline levels in subjects with HP-II reach 1900-2000 units.)



Treatment.

Proline is abundant in nature and readily found in a variety of foods. As a result, attempts to control blood proline levels by restrictive dieting have not succeeded. Patients with childhood neurological manifestations appear to grow out of the pattern of fevers and seizures. Adult life appears to be symptom-free.

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

Phang JM, Yeh GC, Scriver CR. In: Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 7th ed. McGraw-Hill Companies. New York, NY; 1995:1125-26; 1343-44.



JOURNAL ARTICLES

Farrant RD, Walker V, Mills GA, et al. Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. J Biol Chem. 2001;276:15107-116.



Geraghty MT, Vaughan D, Nicholson AJ, et al. Mutations in the Delta1-pyrroline-5-carboxylatedehydrogenase gene cause type II hyperprolinemia. Hum Mol Genet. 1998;7:1411-15.



Cohen SM, Nadler JV. Proline-induced potentiation of glutamate transmission. Brain Res. 1997;761:271-82.



Wajner M, Wannmacher CM, Purkiss P. High urinary excretion of N-(pyrolle-2-carboxyl) glycine in type II hyperprolinemia. Clin Genet. 1990;37:485-89.



Valle D, Goodman SI, Harris SC, et al. Genetic evidence for a common enzyme catalyzing the second step in the degradation of proline and hydroxyproline. J Clin Invest. 1979;64:1365-70.



FROM THE INTERNET

McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 239500: Last Edit Date; 9/10/2002.

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



The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.org



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/



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.