PubMed Health⌕ Search

Biomedical subjects

R Giugliani

Publications and source records attributed to R Giugliani.

At least 73 records · Page 4Linked to original sources
PubMed1996

Maternal hyperphenylalaninaemia as a cause of microcephaly and mental retardation.

We attempted to evaluate the role of maternal hyperphenylalaninaemia (HPA) as an isolated cause of mental retardation and microcephaly in children. This transversal study observed the plasma phenylalanine from mothers of 161 children with mental retardation and/or microcephaly of unknown origin. In this sample, we found two women with previously undiagnosed HPA, a frequency (2/161) higher than expected for our general population (1:12 500) (p < 0.001). We concluded that the plasma phenylalanine levels should be determined during preconceptional evaluation of every woman of reproductive age that already has had a child affected either by mental retardation or microcephaly of unknown cause. It is particularly significant where women currently having their pregnancies have not been screened for phenylketonuria as newborns, as happens in most developing countries.

Adult↗
PubMed1995

Mutations in the galactose-1-phosphate uridyltransferase gene of two families with mild galactosaemia variants.

Classical galactosaemia, deficiency of galactose-1-phosphate uridyltransferase (GALT), is characterized by acute symptoms of hepatomegaly, jaundice, sepsis, cataracts and growth retardation. Treatment with dietary galactose restriction corrects these complications immediately; however, most of these children develop long-term complications of verbal dyspraxia, mental retardation and ovarian failure. Our previous molecular study showed that the most common mutation of the GALT gene is a missense mutation of Q188R (replacement of glutamine-188 by arginine) in approximately 60-65% of the German galactosaemic population. The coding region of GALT was amplified by the polymerase chain reaction from genomic DNA of classical galactosaemic individuals, who are negative or heterozygous for Q188R, and was further characterized by direct sequencing. Three new disease-causing mutations, two missense and a stop codon mutation, were identified in three patients from two families with mild galactosaemic variants: firstly R67C, replacement of arginine-67 by cysteine and W316X, the stop codon at tryptophan-316 in one male; secondly A330V, replacement of alanine-330 by valine in two female siblings. In the first family the patient was also heterozygous for the polymorphism N314D and in the second family both girls were compound heterozygotes for Q188R and A330V. All three galactosaemic individuals have a considerable amount of the residual GALT activity in RBC and the galactose-1-phosphate (GALP) level decreased much faster on treatment than that of other galactosaemic patients with missense mutations such as Q188R. The clinical and biochemical data of these patients were much more favourable in comparison with those of two female galactosaemic individuals, one homozygous for L195P and the other compound heterozygous for Q188R and L195P. These three missense mutations (R67C, L195P and A330V) also occur in highly conserved regions. These observations suggest that the phenotypic variation in galactosaemic individuals may be due to different molecular aetiologies.

Adolescent↗
PubMed1994

Possible high frequency of tetrahydrobiopterin deficiency in south Brazil.

We report our experience with the deficiency of 6-pyruvoyltetrahydropterin synthase, the most common form of tetrahydrobiopterin deficiency. We investigated 5200 patients suspected of having some inborn error of metabolism in a 10-year period, and detected 30 cases (from 28 sibships) of hyperphenylalaninaemias, HPA. From these, 4 sibships (5 patients) were affected by deficiency of 6-pyruvoyltetrahydropterin synthase. All of them were ethnically mixed, with some European ancestry detected in all. The age of diagnosis ranged from 2 to 9 years, and all were initially referred for investigation by having mental retardation and seizures. All of them showed low urinary biopterin levels and a marked elevation of neopterin. Although we detected only a few cases of HPA (30), 5 cases of 6-pyruvoyltetrahydropterin account for almost 20% of this total. The literature, however, reports a proportion of around 0.5%. As the frequency of classical phenylketonuria in our region is similar to that found in Caucasians (1/12,500), we believe that the frequency of this disease in South Brazil may be higher than expected (of the order of 1/400,000). We speculate that this finding could be related to a genetic drift (or founder effect).

Amino Acid Metabolism, Inborn Errors↗
PubMed1994

Pyridoxine-dependent seizures associated with white matter abnormalities.

Pyridoxine-dependent seizures are a disorder of GABA metabolism probably due to a defective binding of pyridoxal phosphate coenzyme (PALP) with glutamate decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis. The resulting GABA deficiency causes severe epilepsy in infancy. We report on a boy with seizures starting soon after birth, and only controlled by pyridoxine at pharmacological dosages. After two months without seizures, a CT scan showed hypodense white matter in frontal and occipital lobes suggestive of a retarded or defective myelination. We are not aware of other descriptions of such morphological abnormalities in a patient with this disorder.

Brain↗
PubMed1993

DNA analysis of cystic fibrosis in Brazil by direct PCR amplification from Guthrie cards.

A 3 bp deletion of codon 508 (phenylalanine) of the cystic fibrosis (CF) gene constitutes the mutation of most CF chromosomes. The frequency of this mutation (referred to as delta F508), varies considerably between populations, ranging from 26% of the CF mutations in Turkey to 88% in Denmark. To determine the frequency of the delta F508 mutation in Brazilian Caucasoid CF patients, we used direct polymerase chain reaction (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards, followed by ethidium bromide staining of gels. Although the overall frequency of the delta F508 mutation was 47% of 380 CF chromosomes from Brazilian Caucasoids born in five different states, significant interstate differences were observed, ranging from a delta F508 frequency of 27% to 53%. While our method could be used to screen patients and their relatives for carrier testing and prenatal diagnosis, the efficacy of screening only for the delta F508 mutation would be low, and would vary from state to state. Screening for a panel of local mutations will be needed to increase the mutation detection rate and optimize genetic counseling.

Base Sequence↗
PubMed1992

Thalamic and basal ganglia hyperdensities--a CT marker for globoid cell leukodystrophy?

Globoid cell leukodystrophy (Krabbe's disease) is a rare autosomal recessive lipidosis, with signs restricted to the nervous system, and is caused by deficiency of the lysosomal hydrolase galactocerebroside beta-galactosidase (galactocerebrosidase). In recent years there have been reports of neurological variants, where age of onset and manifestations differed from the classical form. In other cases, specific CT findings, mainly hyperdensities, have been seen. We report a case of late-infantile Krabbe's disease where thalamic and basal ganglia hyperdensities have been seen on CT scan. We also stress that clinicians should be aware of the possibility of Krabbe's disease in infants who display progressive encephalopathy and these CT findings.

Basal Ganglia↗
PubMed1992

Biochemical investigation of a Brazilian patient with a defect in mitochondrial acetoacetylcoenzyme-A thiolase.

A case report of 3-ketothiolase deficiency due to a defect of mitochondrial acetoacetyl-CoA thiolase protein in a Brazilian boy and its biochemical investigation is presented. The child had moderate generalized hypotonia, EEG alterations and crises of metabolic acidosis following infections. Hypotonia and EEG abnormalities disappeared with a low protein diet, and physical and mental development are normal. Urinary organic acid excretion was typical of 3-ketothiolase deficiency, showing consistently high levels of 2-methyl-3-hydroxybutyric acid and tiglylglycine. Activation of acetoacetyl-CoA thiolase activity by potassium (K) ion in cultured fibroblasts was not observed, demonstrating the lack of activity of mitochondrial acetoacetyl-CoA thiolase. In addition, the signal for the mitochondrial acetoacetyl-CoA thiolase protein was undetectable in the immunoblot analysis. In the pulse-chase experiments, the signal for mitochondrial acetoacetyl-CoA thiolase was detected after a 1-h pulse but not after a 24-h chase. These results indicate that the deficiency was caused by an unstable mitochondrial acetoacetyl-CoA thiolase protein.

Acetyl-CoA C-Acetyltransferase↗
PubMed1992

Sea-blue histiocytosis in a family with Niemann-Pick disease. A clinical, morphological and biochemical study.

Four siblings of a large Brazilian kindred are shown to have a variant of Niemann-Pick disease masquerading as the sea-blue histiocyte syndrome. They show a very similar clinical and laboratory picture: massive hepatosplenomegaly, low height for age, diffuse interstitial pulmonary infiltration, high levels of serum acid phosphatase and sea-blue histiocytes in the bone marrow. The neurological examination, as well as the retinae and maculae are normal. The high-density lipoprotein serum cholesterolemia ranged from 8.6 to 13.9 mg/dl, much lower than the 5th centile of normal distribution. The AI apolipoprotein concentrations in two siblings (0.29 and 0.44 g/l) were also below the minimal reference level of 0.90 g/l. The histochemical reactions demonstrated that sphingomyelin and ceroid are the accumulating substances in the marrow histiocytes. Electron microscopically, the cytoplasmatic granules of the histiocytes are phagolysosomes which contain scarce amorphous material, loose arranged lamellae, or dense well-organized structures with a fingerprint or fine network pattern. The sphingomyelinase activity in leucocyte extracts ranged from 4.9 to 8.6% and in cultured fibroblast extracts from 7.7 to 10% of simultaneous controls. The activity of other lysosomal enzymes was normal. Accordingly, this variant of Niemann-Pick disease should be classified as chronic nonneuronopathic sphingomyelinase-deficient type. The present data suggest that this variant is inherited as an autosomal recessive character. Our findings support the view that the sea-blue histiocyte syndrome is not an independent entity.

Adolescent↗
PubMed1991

CT hypodensity on cerebral white matter in Wilson's disease.

Wilson's disease in an autosomal recessive disorder of copper metabolism where systemic manifestations are secondary to the accumulation of copper in hepatic, nervous and other tissues. In CNS, the structural lesions most commonly found by CT scan are ventricular dilatation, cortical atrophy, basal ganglia hyperdensities, and brainstem and cerebellar atrophy. Degenerative changes of cerebral white matter seen on early anatomo-pathologic studies, but were almost never found on CT scan from recently described patients. We report a case of Wilson's disease with an unusually rapid deterioration where asymmetric low-densities in the subcortical white matter were disclosed by CT scan.

Adolescent↗
PubMed1990

Application of a flowchart for the detection of lysosomal storage diseases in 105 high-risk Brazilian patients.

Lysosomal storage diseases (LSD) are a group of more than 40 disorders, many of them with overlapping phenotype, in which clinical diagnosis is often difficult. Definitive diagnosis is based on enzyme assays, a large number of such assays usually being necessary during the investigation of each patient. In addition, there will frequently be a need for tissue culture in order to provide enough material for analysis. Taking into account these difficulties, we designed a flowchart for the detection of LSD that is based on 2 sets of tests requiring only random urine and heparinized blood. Here we describe this routine and report the results of its application to 105 Brazilian patients in whom a LSD was suspected. We think that the application of this rationale represents a saving of work and costs, and should be of special interest to genetic centers in developing countries.

Brazil↗
PubMed1990

Very low levels of high density lipoprotein cholesterol in four sibs of a family with non-neuropathic Niemann-Pick disease and sea-blue histiocytosis.

Very low serum levels of high density lipoprotein cholesterol ranging from 8.6 to 13.9 mg/dl were detected in four out of 12 sibs of a Brazilian kindred with the non-neuropathic form of Niemann-Pick disease. Hepatosplenomegaly, interstitial infiltration of the lungs, absence of neurological signs, sea-blue histiocytes in the bone marrow and liver, and high values for serum acid phosphatase (18 to 32 U/l) were common to all affected children. Leucocyte acid sphingomyelinase activity ranged from 3.6 to 6.5% of mean control values, and fibroblast activity from 9 to 13% of mean controls. The parents had low-normal levels. The relationship between these findings is unclear and deserves further investigation.

Acetylesterase↗
PubMed1990

Early and unusual presentation of type I primary hyperoxaluria.

Oxalosis, the systemic deposition of calcium oxalate crystals, may occur in several hyperoxaluric states due to increased production or absorption of oxalate. Type I primary hyperoxaluria (PH I) is a rare autosomal recessive disease caused by deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase. Most patients with this disorder are noticed in mid-childhood or even later due to symptoms related to urinary stone disease. In this paper, we report a patient with PH I with a rapid downhill progression to renal failure and death. Oxalosis was detected by renal biopsy, and the diagnosis of PH I was confirmed by increased urinary oxalate and glycolate levels.

Acute Kidney Injury↗
PubMed1989

Inborn errors of metabolism. Sensitivity of screening tests in high risk patients.

We estimated the sensitivity of a screening procedure (SP) for inborn errors of metabolism (IEM) in 566 referred, high-risk patients. The 143 (25.3% of the total sample) patients with initial abnormal results in at least one screening test (ST) were recalled for further investigations. An IEM was diagnosed in 40.6 percent of the 106 patients who came for reevaluation. In 114 of the remaining 423 patients who had normal initial ST, an IEM was still suspected on basis of clinical, radiological, and/or laboratory findings and was confirmed in 30 of such patients (5.3% of the total sample and 7.1% of the patients with normal results in the SP). The sensitivity of the SP was estimated maximally as 67.4 percent and the efficiency as 80.4 percent. Twenty-five of the 30 cases undetected with the SP were patients with sphingolipidoses. The simple inclusion of thin-layer chromatography of urinary oligosaccharides in the SP should allow the detection of at least one half of these cases, increasing its sensitivity by 14.1 percent and its efficiency by 4.6 percent. In at least 7.1 percent of patients with an initial normal ST, an IEM was detected. These would have remained undiagnosed if the limitations of the SP employed had not been fully understood.

Child↗
PubMed1987

An evaluation of four methods for the detection of heterozygous cystinuria.

Heterozygotes for cystinuria (types II and III) may be detected on the basis of slight to moderate elevations in urinary cystine, lysine and sometimes arginine. This seems to be a common genetic trait, and there are indications of an increased risk of urinary stone disease. In order to test the sensitivity and reliability of the procedures normally used for screening and diagnosis of heterozygous cystinuria, we studied 32 heterozygotes previously diagnosed by ion-exchange chromatography of urinary amino acids, and 23 healthy individuals. A random urine sample from each subject was analysed using the cyanide-nitroprusside test, thin-layer amino acid chromatography, colorimetric estimations of cystine and lysine, and ion-exchange amino acid chromatography. Thin-layer chromatography provided the highest sensitivity. Thus the frequency of heterozygotes calculated in previous studies, based on screening by the cyanide-nitroprusside test, may be under-estimated. The colorimetric estimations of cystine and lysine provided low sensitivity as screening tests and, compared with the ion-exchange chromatography, were unreliable diagnostic methods.

Chromatography, Ion Exchange↗
PubMed1987

Congenital malformations detected in 731 autopsies of children aged 0 to 14 years.

A retrospective study of 731 autopsies of children aged 0 to 14 years, performed in the Pathological Anatomy Service of the University Hospital of Porto Alegre from 1977 to 1982, was carried out to determine the frequency, type, and seriousness of congenital malformations. The subjects were divided into five age ranges: stillborn (6), 0 to 24 hours (42), 1 to 30 days (50), 1 to 12 months (24), and 1 to 14 years (9). The malformations were classified as single or multiple (presence of two or more independent defects), and their contribution to death was evaluated. Congenital malformations were detected in 131 autopsies (18%). In most cases the defects were single (91), and the most common ones involved the cardiovascular system (37) and the genitourinary system (21). In the patients with multiple malformations (40), the cardiovascular system (24) and the genitourinary system (19) were also most frequently involved. Defects of the osteoarticular system were also frequently encountered in patients with multiple defects (25), although most of them were deformations caused by mechanical factors. Proportionally, congenital malformations were most frequently detected in the 0 to 24 hours range, which also included the highest proportion of multiple defects in relation to single ones (1:1). Congenital malformations were considered responsible for death in 76% of the 131 cases (87% of the multiple defects patients and 60% of the single defect patients). We believe that the data collected in the present study may contribute to a better understanding of the role played by congenital malformations in child mortality.

Abnormalities, Multiple↗