Instituto Valenciano de Microbiología
(IVAMI)

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
Email: 
www.ivami.com
CIF B-96337217

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Adenine phosphoribosyltransferase deficiency of ... (Adenine phosphoribosyltransferase deficiency) - Gen aprt.

Deficiency phosphoribosyltransferase (APRT) is an inherited disease that affects the kidneys and urinary tract. The most common feature of this disorder is the formation of kidney stones, which can create obstructions in the urinary tract, causing pain and difficulty Miccio.

Signs and symptoms of the disease can occur any time from infancy to late adulthood, although half of those affected have the first symptoms in adulthood. When the disease occurs in childhood, the first sign is usually the presence of small clots reddish brown in diaper newborn caused by the passage of stones. Later, in the mid to late childhood, renal and urinary tract stones can cause problems with kidney function. In adulthood, the first symptoms usually kidney stones and urinary problems. Other signs and symptoms of deficiency phosphoribosyltransferase (APRT) include fever, urinary tract infection, hematuria, abdominal cramps, nausea and vomiting. Without treatment, renal function may decrease, which can lead to end - stage renal disease (ESRD), in which the kidneys are no longer able to effectively filter fluids and waste products from the organism. The characteristics of this disease and its severity vary greatly among affected individuals, even among members of the same family. It is estimated that between 15% and 20% of people with phosphoribosyltransferase deficiency has no signs or symptoms of the disease.

This process is due to mutations in the APRT gene located on long arm of chromosome 16 (16q24). This gene encodes an enzyme called adenine phosphoribosyltransferase (APRT). This enzyme is encoded in all cells and is part of the salvage pathway of purine, purine recycling to form a molecule of adenosine monophosphate (AMP). This conversion occurs when AMP is needed as an energy source for cells.

They have identified at least 40 mutations in the APRT gene in people with adenine phosphoribosyltransferase deficiency. Most of these mutations change amino acids used in the synthesis of the enzyme. These mutations fall into two groups known as allele APRT * J allele and APRT * Q0. The APRT * J allele comprising a mutation that replaces the amino acid methionine threonine by amino acid at position 136 in the enzyme APRT (Met136Thr or M136T). This mutation reduces enzyme function. The M136T mutation occurs almost exclusively in Japanese individuals. Individuals most affected have this mutation in both copies of the aprt gene in each cell. The APRT * Q0 allele consists of all other aprt gene mutations. The most common of these mutations (IVS4 + 2insT) alters encoding the enzyme, which results in an abnormally short, nonfunctional enzyme. This mutation is estimated to occur in 40% of Europeans affected. APRT gene mutations result in a functional enzyme deficiency that prevents conversion adenine to adenosine monophosphate. Consequently, adenine is converted to another molecule called 2,8-dihydroxyadenine (2,8-DHA), which crystallizes in the urine, forming kidney stones and urinary tract. As a result, the renal function may decrease, which can lead to end stage renal disease (ESRD), endangering the life of renal function.

This disease is inherited in an autosomal recessive pattern, that is, 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 deficiency phosphoribosyltransferase (APRT), by complete PCR amplification of exons APRT 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).