Prolidase deficiency of ... (Prolidase deficiency) - Gen DPEP
Prolidase deficiency is a disorder that results in a wide variety of symptoms. The severity of symptoms varies greatly among affected individuals affected others and some people have no symptoms.
Signs and symptoms associated generally occur during childhood and may include splenomegaly or hepatosplenomegaly; diarrhea, vomiting and dehydration; susceptibility to severe skin infections, ear or airway. Some individuals may develop chronic lung disease. The characteristic facial features of people with deficiency include prominent prolidase hipertelorismo eyes, a high forehead, a flat nasal bridge, and micrognathia. Affected children may exhibit developmental delay, and about 75 percent say intellectual disability that can range from mild to severe. Often, people with deficiency prolidase develop skin lesions, especially in their hands, feet, calves and face. The severity of involvement of the skin, which usually begins in childhood, may vary from a mild rash to severe skin ulcers. Ulcers on the skin, especially in the legs, can not be completely cured, leading to complications including infection and amputation.
Prolidase deficiency is due to mutations in the gene DPEP (peptidase D), located on the long arm of chromosome 19 (19q13.11) encoding prolidase enzyme, also called peptidase D. This enzyme helps break certain dipeptides. Specifically, prolidase divided dipeptides containing proline or hydroxyproline amino acids. By releasing these amino acids, the prolidase helps make them available for use in the synthesis of proteins that the body needs. Prolidase is also involved in the final step of the breakdown of certain proteins obtained from the diet and proteins that are no longer needed in the body. Prolidase is particularly important in the degradation of collagen, a family of proteins rich in proline and hydroxyproline. Collagens are an important part of the extracellular matrix, which reinforces and supports the connective tissues such as skin, bone, cartilage, tendons and ligaments. Collagen degradation occurs during remodeling of the extracellular matrix.
They have identified at least 19 mutations in the gene in people DPEP deficient prolidase. These genetic changes lead to loss of enzyme activity prolidase. Although not well understood how the absence of prolidase activity is responsible for the various signs and symptoms of deficiency prolidase, it has been suggested that the accumulation of dipeptide that have not been degraded can lead to cell death. When cells die, their contents are released into the surrounding tissue, which can cause inflammation and lead to skin problems seen in prolidase deficiency. The deterioration of the collagen degradation during remodeling of the extracellular matrix may also contribute to skin problems. Intellectual disability may be due to problems in the processing of neuropeptides. It is unclear how the absence of prolidase activity causes the other features of the disease.
This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with prolidase deficient, by complete PCR amplification of the exons of DPEP gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).