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Biomedical subjects

R Cerone

Publications and source records attributed to R Cerone.

At least 19 recordsLinked to original sources
PubMed1999

Phenylketonuria: diet for life or not?

In order to evaluate the argument whether or not a restricted phenylalanine diet should be maintained for life in patients with phenylketonuria (PKU), 16 patients with early treated PKU but off diet since their 11th birthday were investigated. The evaluation included a detailed neurological examination, IQ, neurophysiological testing and MRI of the brain. Even if IQ and electrophysiological studies were normal or unchanged if compared to results before diet discontinuation, all patients revealed abnormal neurological signs. We conclude that the diet should be continued during adult life, but somewhat higher phenylalanine levels (<10mg/dl;<600 micromol/l) than at younger ages should be allowed.

Age Factors↗
PubMed1998

Determination of plasma and serum homocysteine by high-performance liquid chromatography with fluorescence detection.

Determination of homocysteine in plasma or serum is becoming an important diagnostic procedure. Accurate, rapid and low cost methods for measuring homocysteine are therefore required. We have improved an HPLC method and made it suitable for clinical application. The total homocysteine in plasma consists of free homocysteine (i.e., reduced plus oxidized homocysteine in the non-protein fraction of plasma) and protein-bound homocysteine. The method consists of the following steps: reduction of the sample with tri-n-butylphosphine, precipitation of proteins with trichloroacetic acid (10%) and derivatization with ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate. The derivatives are separated by reversed-phase high-performance liquid chromatography followed by fluorescence detection. The concentrations (mean +/- S.D.) of total homocysteine in plasma from 77 normal subjects, 44 male and 33 female adults, were 8.4 +/- 2.15 and 7.1 +/- 1.18 mumol/l, respectively. Serum concentrations were 8.8 +/- 2.6 mumol/l in males and 7.6 +/- 1.5 mumol/l in females.

Chromatography, High Pressure Liquid↗
PubMed1998

Eight new mutations of the phenylalanine hydroxylase gene in Italian patients with hyperphenylalaninemia.

This report identifies eight new mutations of the phenylalanine hydroxylase gene detected in Italian patients with hyperphenylalaninemia. The trivial name of the mutations, predicted phenotypic effect, and population of origin (Italian region) are as follows: F55L (nonconservative change: classic, moderate, mild PKU ?; Sicily), IVS2nt-13 (splicing defect, classic PKU; Tuscany), I65N (nonconservative change classic, moderate, mild PKU ?; Sicily), H201Y (non-PKU HPA; Sicily), I269L (non-PKU HPA, or polymorphism; Sicily), IVS7nt3 (splicing defect or polymorphism; Sicily), I283N (classic PKU; Sicily), IVS12nt2 (splicing defect, classic PKU; Sicily and Apulia). In Sicily, the relative frequency of mutations F55L, I65N, H201Y, I269L, IVS7nt3, I283N, IVS12nt2 is < 1%. The seven new mutations identified in the Sicilian population increase the remarkable genetic heterogeneity typical of this population with an estimated homozygosity value at the PAH locus of 0.041.

Adolescent↗
PubMed1998

Purines and pyrimidines determination in urine using high-performance liquid chromatography.

Single purine and pyrimidine bases are involved in two fundamental metabolic pathways that lead to formation of the building stones of DNA and RNA. Purine and pyrimidine nucleotides are also critically important metabolites in many cellular functions. The main breakdown of purines and pyrimidines produces uric acid and B-minoacids, respectively. Therefore, the study of purine and pyrimidine compounds in body fluid has high clinical relevance. We report, in this work, our experience in purines and pyrimidines determination in urine from children presenting with a clinical picture suggesting an inborn these pathways.

Biomarkers↗
PubMed1997

Severe complex I deficiency in a case of neonatal-onset lactic acidosis and fatal liver failure.

We report a newborn admitted to our service on the 2nd day of life because of hypotonia and metabolic acidosis. A progressive hepatocellular dysfunction dominated the clinical picture and the patient died at 13 months of age because of severe hepatic failure. Persistent lactic acidosis, high ketone bodies levels and high-normal lactate/pyruvate and 3-hydroxybutyrate/acetoacetate molar ratios in plasma were found. Investigation of a liver biopsy revealed low activities of all the mitochondrial respiratory chain enzymes but in particular a marked decrease of complex I (NADH cytochrome c reductase) activity. All respiratory chain enzyme activities were normal in cultured skin fibroblasts. Mitochondrial DNA analysis failed to detect any major rearrangements. Although only a few cases have been reported so far, it is becoming clear that liver should be considered as one of the organs involved in oxidative phosphorylation disorders. The finding of unexplained progressive liver failure with poor neurological conditions, lactic acidaemia and ketonuria strongly warrants investigation for a respiratory chain disorder. Moreover, the finding of normal respiratory enzyme activities in a tissue other than liver does not rule out the existence of an oxidative phosphorylation disorder in patients with hepatocellular disease of unexplained origin.

Acidosis, Lactic↗
PubMed1997

Tyrosinemia type III: diagnosis and ten-year follow-up.

Tyrosinemia type III, caused by deficiency of 4-hydroxyphenylpyruvate dioxygenase, is a rare disorder of tyrosine catabolism. Primary 4-hydroxyphenylpyruvate dioxygenase deficiency has been described in only three patients. The biochemical phenotype shows hypertyrosinemia and elevated urinary excretion of 4-hydroxyphenyl derivatives. We report the clinical and biochemical findings and the results of long-term follow-up in a new patient with this disorder presenting with severe mental retardation and neurological abnormalities. The clinical phenotype is compared with those reported in the three previously described patients.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1994

Maple syrup urine disease (MSUD): screening for known mutations in Italian patients.

Maple syrup urine disease (MSUD) is an autosomal recessive disease due to deficiency of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) caused by a large number of mutations. In the present study, DNA from Italian patients and their relatives was examined for three point mutations (Y393N in the E1 alpha gene, T841G and G1031A in the E2 gene) and two deletions (-G at the intron/exon border of exon 8 in the E2 gene and an 11 bp deletion in exon 1 of the E1 beta gene) using the polymerase chain reaction (PCR) followed by allele-specific oligonucleotide (ASO) hybridization, gene-scanning size analysis of fluorescent-tagged PCR products and/or automated DNA sequence analysis. Our results show that two different mutations account for 7 of the 20 mutant MSUD alleles. Two unrelated affected children, two of their parents and one sibling were carriers for the 11 bp deletion in the E1 beta gene, one patient and her mother were heterozygous for Y393N in E1 alpha, while T841G, G1031A and the -G deletion in E2 were not detected. This study is the first attempt to characterize at a nucleic acid level MSUD mutations in Italy. Our results indicate that additional defects are present in the Italian population and that, unlike the Mennonites, a number of different MSUD mutations exist in Italians.

Alleles↗
PubMed1992

Biochemical diagnosis and outcome of 2 years treatment in a patient with combined methylmalonic aciduria and homocystinuria.

We describe a patient with methylmalonic aciduria and homocystinuria due to a defect in cobalamin metabolism of the Cbl-C type mutant (McKusick 277400). Our case was diagnosed within the first 2 months of life by amino acid analysis (ion-exchange chromatography) and by biochemical studies in cultured fibroblasts ([14C]propionate incorporation, methionine and serine formation). We discuss the clinical course and the biochemical evolution after 2 years of hydroxycobalamin treatment that led to an improvement in general clinical condition and neurological performance.

Amino Acids↗
PubMed1992

The pathobiochemistry of uremia and hyperargininemia further demonstrates a metabolic relationship between urea and guanidinosuccinic acid.

To better understand the biosynthesis of guanidinosuccinic acid, we determined urea, arginine, and guanidinosuccinic acid levels in nondialyzed uremic and hyperargininemic patients. These substances were also determined during several years of therapy in one hyperarginiemic patient. Interrelationships of guanidinosuccinic acid levels with their corresponding urea and arginine levels were assessed by linear correlation studies. In uremic patients, a significant positive linear correlation (r = .821, p less than .001) was found between serum urea and guanidinosuccinic acid levels A significant positive linear correlation was also found between serum urea levels and urinary guanidinosuccinic acid levels (r = .828, P less than .001), but not between serum arginine levels and urinary guanidinosuccinic acid levels in hyperargininemic patients. In the intrahyperargininemic patient study, a similar significant positive correlation was found between serum urea levels and the corresponding urinary guanidinosuccinic acid levels (r = .866, P less than .001); the correlation between serum arginine levels and the corresponding urinary guanidinosuccinic acid levels was smaller. The presented analytical findings in uremic and hyperargininemic patients clearly demonstrate a metabolic relationship between urea and guanidinosuccinic acid.

Adult↗
PubMed1991

Phenylketonuria missense mutations in the Mediterranean.

Two missense mutations have been identified in the phenylalanine hydroxylase (PAH) genes of an Italian phenylketonuria (PKU) patient. Both mutations occurred in exon 7 of the PAH gene, resulting in the substitution of Trp for Arg at amino acid 252 (R252W) and of Leu for Pro (P281L) at amino acid 281 of the protein. Expression vectors containing either the normal human PAH cDNA or mutant cDNAs were constructed and transfected into cultured mammalian cells. Extracts from cells transfected with either mutant construct showed negligible enzyme activity and undetectable levels of immunoreactive PAH protein as compared to the normal construct. These results are compatible with the severe classical PKU phenotype observed in this patient. Population genetic studies in the Italian population revealed that both the R252W and the P281L mutations are in linkage disequilibrium with mutant restriction fragment length polymorphism (RFLP) haplotype 1, which is the most prevalent RFLP haplotype in this population. The R252W mutation is present in 10% and the P281L mutation is present in 20% of haplotype 1 mutant chromosomes. These mutations are both very rare among other European populations, suggesting a Mediterranean origin for these mutant chromosomes.

Base Sequence↗