Última actualización:
May 22, 2008
Años publicados: 1988, 1989, 2003
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.
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.
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.
Hyperprolinemia Type II is a very rare disorder that is present at birth. It affects males and females in equal numbers.
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.
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
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.
NORD y la Fundación MedicAlert se han asociado en un nuevo programa para brindar protección a pacientes con enfermedades raras en situaciones de emergencia.
Aprende más https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Asegurarse de que los pacientes y los cuidadores estén equipados con las herramientas que necesitan para vivir su mejor vida mientras manejan su condición rara es una parte vital de la misión de NORD.
Aprende más https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/Este programa de asistencia, primero en su tipo, está diseñado para los cuidadores de un niño o adulto diagnosticado con un trastorno raro.
Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/