Two types of hyperprolinemia are recognized by physicians and clinical researchers. Each represents an inherited inborn error of metabolism involving the amino acid, proline. Proline is abundant in nature and readily found in a variety of foods.
Hyperprolinemia Type I (HP-I) is characterized by abnormally high levels of proline in the blood. The high level of blood proline is the result of a deficiency of the enzyme proline oxidase, which is essential to the normal breakdown (metabolism) of proline. There are often no clinical manifestations of HP-1.
Hyperprolinemia II (HP-II) results from the deficiency of another enzyme and also results in high blood proline levels, as well as other more severe clinical manifestations than are seen in HP-I. Mild mental retardation and convulsions are commonly associated with HP-II.
Hyperprolinemia Type I is the result of proline oxidase deficiency and is characterized by an abnormally high proline blood level. Levels of the amino acids hydroxyproline and glycine in the blood are also higher than normal. Some clinicians believe that kidney abnormalities may be associated with HP-I, although this is disputed. The signs and symptoms of HP-I, other than the high levels of amino acids in the blood and urine, are vague. Often, this disorder is described as benign.
Hyperprolinemia Type I is an autosomal recessive disorder. The gene involved is located on the long arm of chromosome 22. 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 22q11.2 refers to band 11 on the long arm of chromosome 22.
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.
Hyperprolinemia Type I is a very rare disorder that is present at birth. It affects males and females in equal numbers.
HP-I is recognized by elevated blood proline levels. (The normal level is approximately 450 units, but people with HP-1 may have levels of 1900 to 2000 units.. Often, the diagnosis is made by exclusion. After failure to arrive at a diagnosis by other means, a blood proline level is ordered. The result confirms the diagnosis.
Because proline is so widespread among foods, attempts to control blood proline levels by restrictive dieting have not succeeded. Because the medical consequences of this particular inborn error of metabolism appear to be modest or inconsequential, many physicians do not take an aggressive approach toward treatment.
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McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 239500: Last Edit Date; 9/10/2002.