1990 Fiscal Year Final Research Report Summary
Biochemical Mechanisms for Clinical Symptomes in Purine Metabolizing Enzyme Deficier Deficiencies.
| Project/Area Number |
63570286
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Tokyo University of Foregn Studies (1989-1990)
Tokyo Medical and Dental University (1988) |
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Principal Investigator |
NISHIDA Yutaro Tokyo University of Foregn Studies, Health Administration Center, Professor, 保健管理センター, 教授 (20114598)
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| Project Period (FY) |
1988 – 1990
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| Keywords | HGPRT deficiency / APRT deficiency / Purine metabolizing enzymes / Hyperuricemia / Liposome / Creatinine / Gout / Methylation |
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| Research Abstract |
1. Although Hypoxanthine Guanine Phospho-Ribosyl-Transferase (HGPRT) and Adenine Phospho-Ribosyl-Transferse (APRT) deficiencies are extremely rare, an early diagnosis is required to prevent renal damage. Simple screening methods for the detection og HGPRT and/or APRT deficiencies using dried filter paper blood and/or urine spots were established.
2. Enzyme activity related to purine metabolism in the digestive juices of human was measured. Bile, pancreatic juces and saliva showed enzyme activities such as 5'-nucleotidase, adenosine deaminase, purine nucleosidephosphorylase, and xanthine oxidase. Oral administration of enzymes related to purine catabolism in chickins caused significant decrease in plasma uric acid level.
3. Erythrocyte PRPP availavitity for adenine was measured by silicon oil method. This method is useful for differential diagnosis between heterozygote of complete APRT deficiency and homozygote of partial APRT deficiency.
4. Five unrelated patients with HPRT deficiency were analyzed to understand the spectrum of molecular defects using Southern blot, polymerase chain amplification ofHGPRT mRNA and sequencing, and oligonucleotide hybridization analysis of the HPRT gene. Sequencing analysis of amplified DNA from three different patients with HPRT deficiency implied three unique molecular abnormalities : 1) one single-base substitution at codon 54 from ATG to CTG, 2) two single-base substitutions at codon 179 from GTT to GGT at and codon 180 from GGA to AGA , and 3) 51 nucleotide deletion between nucleotides 747 a
nd 797.
5. Close correlation between creatinine and uric acid synthesis was found. In addition, it was suggested that accelerated uric acid synthesis seen in some gouty patients is due to increased creatinine synthesis.
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