Browsing by Author "Valongo, C."
Now showing 1 - 7 of 7
Results Per Page
Sort Options
- Complex phenotype of hypercholesterolaemia in a family with both ABCG8 and APOB mutationsPublication . Padeira, G.; Gomes, I.; Correia, C.; Valongo, C.; Alves, A.C.; Medeiros, A.; Bourbon, M.; Ferreira, A.C.Familial Hypercholesterolemia (FH) is the most common of all genetic hypercholesterolaemias with defects in LDLR, APOB and PCSK9 accounting for the majority of cases. However, there are other rare disorders like sitosterolaemia that can present the same phenotype. Both can cause premature atherosclerosis but have distinctive dietetic and therapeutic intervention.
- Deficiencia de glicerolcinasa: una causa metabólica de retraso global del desarrolloPublication . Ribeiro, A.I.; Pinto, S.; Ayres-Pereira, I.; Vieira, A.; Valongo, C.; Passas, A.; Lopes, A.; Santos, H.La deficiencia de glicerolcinasa (GKD) es un raro trastorno recesivo ligado al X, caracterizado por la pérdida de la función del enzima glicerolcinasa (GK), que cataliza la fosforilación dietética del glicerol a glicerol-3-fosfato, necesario en la síntesis de lípidos y en la gluconeogénesis [1,2]. La pérdida de actividad enzimática conduce a una acumulación de glicerol en suero (hiperglicerolemia) y orina (gliceroluria). (...)
- Indoor levels and health risk assessment of volatile organic compounds in Portuguese homesPublication . Slezakova, K.; Costa, C.; Valongo, C.; Teixeira, J.P.; Madureira, J.About indoor levels and health risk assessment of volatile organic compounds in Portuguese homes.
- Molecular picture of cobalamin C/D defects before and after newborn screening eraPublication . Nogueira, C.; Marcão, A.; Rocha, H.; Sousa, C.; Fonseca, H.; Valongo, C.; Vilarinho, L.Objective: Birth prevalence of Cobalamin (Cbl) C or D defects in Portugal is an estimated 1:85,000, one of the highest worldwide. We compared the genotype/phenotype of patients identified with CblC or CblD before and after the implementation of expanded newborn screening. Methods: Twenty-five Portuguese CblC/D patients, 14 symptomatic and 11 identified through screening, were diagnosed using gas chromatography or tandem mass spectrometry. Molecular characterization was performed through the study of MMACHC and MMADHC genes. Results: The most common MMACHC mutation, c.271dupA, was present in 100% of MMACHC alleles of all CblC screened patients, in contrast with the 61% identified before expanded newborn screening. All studied cases (except one, who presented a CblD deficiency) presented a CblC defect. More CblC late-onset patients were diagnosed before the introduction of newborn screening than in the post newborn screening era, probably because some early onset patients died without a definitive diagnosis. Conclusion: The molecular data found in this cohort contribute to the improvement of screening and diagnosis of Cbl defects and would enable a confirmatory diagnosis of these patients, reducing the need for complex, costly, laborious, and time-consuming biochemical/enzymatic tests.
- A Novel SUCLA2 Mutation in a Portuguese Child Associated With "Mild" Methylmalonic AciduriaPublication . Nogueira, Célia; Meschini, M.C.; Nesti, C.; Garcia, P.; Diogo, L.; Valongo, C.; Costa, R.; Videira, A.; Vilarinho, L.; Santorelli, F.M.Succinyl-coenzyme A synthase is a mitochondrial matrix enzyme that catalyzes the reversible synthesis of succinate and adenosine triphosphate (ATP) from succinyl-coenzyme A and adenosine diphosphate (ADP) in the tricarboxylic acid cycle. This enzyme is made up of α and β subunits encoded by SUCLG1 and SUCLA2, respectively. We present a child with severe muscular hypotonia, dystonia, failure to thrive, sensorineural deafness, and dysmorphism. Metabolic investigations disclosed hyperlactacidemia, moderate urinary excretion of methylmalonic acid, and elevated levels of C4-dicarboxylic carnitine in blood. We identified a novel homozygous p.M329V in SUCLA2. In cultured cells, the p.M329V resulted in a reduced amount of the SUCLA2 protein, impaired production of mitochondrial ATP, and enhanced production of reactive oxygen species, which was partially reduced by using 5-aminoimidazole-4-carboxamide ribonucleotide in the culture medium. Expanding the array of SUCLA2 mutations, we suggested that reactive oxygen species scavengers are likely to impact on disease prognosis.
- Phenotype and genotype in 101 males with X-linked creatine transporter deficiencyPublication . van de Kamp, J.M.; Betsalel, O.T.; Mercimek-Mahmutoglu, S.; Abulhoul, L.; Grünewald, S.; Anselm, I.; Azzouz, H.; Bratkovic, D.; de Brouwer, A.; Hamel, B.; Kleefstra, T.; Yntema, H.; Campistol, J.; Vilaseca, M.A.; Cheillan, D.; D'Hooghe, M.; Diogo, L.; Garcia, P.; Valongo, C.; Fonseca, M.; Frints, S.; Wilcken, B.; von der Haar, S.; Meijers-Heijboer, H.E.; Hofstede, F.; Johnson, D.; Kant, S.G.; Lion-Francois, L.; Pitelet, G.; Longo, N.; Maat-Kievit, J.A.; Monteiro, J.P.; Munnich, A.; Muntau, A.C.; Nassogne, M.C.; Osaka, H.; Ounap, K.; Pinard, J.M.; Quijano-Roy, S.; Poggenburg, I.; Poplawski, N.; Abdul-Rahman, O.; Ribes, A.; Arias, A.; Yaplito-Lee, J.; Schulze, A.; Schwartz, C.E.; Schwenger, S.; Soares, G.; Sznajer, Y.; Valayannopoulos, V.; Van Esch, H.; Waltz, S.; Wamelink, M.M.; Pouwels, P.J.; Errami, A.; van der Knaap, M.S.; Jakobs, C.; Mancini, G.M.; Salomons, G.S.BACKGROUND: Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype--genotype correlation has been lacking. METHODS: We performed a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation in the creatine transporter gene (SLC6A8). RESULTS AND CONCLUSIONS: Most patients developed moderate to severe intellectual disability; mild intellectual disability was rare in adult patients. Speech language development was especially delayed but almost a third of the patients were able to speak in sentences. Besides behavioural problems and seizures, mild to moderate motor dysfunction, including extrapyramidal movement abnormalities, and gastrointestinal problems were frequent clinical features. Urinary creatine to creatinine ratio proved to be a reliable screening method besides MR spectroscopy, molecular genetic testing and creatine uptake studies, allowing definition of diagnostic guidelines. A third of patients had a de novo mutation in the SLC6A8 gene. Mothers with an affected son with a de novo mutation should be counselled about a recurrence risk in further pregnancies due to the possibility of low level somatic or germline mosaicism. Missense mutations with residual activity might be associated with a milder phenotype and large deletions extending beyond the 3' end of the SLC6A8 gene with a more severe phenotype. Evaluation of the biochemical phenotype revealed unexpected high creatine levels in cerebrospinal fluid suggesting that the brain is able to synthesise creatine and that the cerebral creatine deficiency is caused by a defect in the reuptake of creatine within the neurones
- Sitosterolémia - uma causa rara de uma situação comumPublication . Garcia, A.M.; Padeira, G.; Conde, M.; Carvalho, R.; João, A.; Gomes, I.; Bosquet, Lucas G.; Correia, C.; Valongo, C.; Dias, A.; Medeiros, A.; Bourbon, Mafalda; Ferreira, A.C.Introdução: A Sitosterolémia (OMIM 210250) é uma doença autossómica recessiva rara do metabolismo dos esteróis vegetais. É causada por mutações nos genes ABCG5 ou ABCG8 (2p21) que codificam as proteínas esterolina 1 e 2 do transportador ABC (ATP-binding cassette), com consequente comprometimento da excreção intestinal e biliar de esteróis e sua acumulação no sangue e tecidos. Clinicamente é caracterizada pela presença de xantomas, níveis elevados de colesterol e aterosclerose prematura, fazendo diagnóstico diferencial com a Hipercolesterolémia Familiar.