ABSTRACT
BACKGROUND: Tyrosinemia type II, also known as Richner-Hanhart Syndrome, is an extremely rare autosomal recessive disorder, caused by mutations in the gene encoding hepatic cytosolic tyrosine aminotransferase, leading to the accumulation of tyrosine and its metabolites which cause ocular and skin lesions, that may be accompanied by neurological manifestations, mostly intellectual disability. AIMS: To update disease-causing mutations and current clinical knowledge of the disease. MATERIALS AND METHODS: Genetic and clinical information were obtained from a collection of both unreported and previously reported cases. RESULTS: We report 106 families, represented by 143 individuals, carrying a total of 36 genetic variants, 11 of them not previously known to be associated with the disease. Variants include 3 large deletions, 21 non-synonymous and 5 nonsense amino-acid changes, 5 frameshifts and 2 splice variants. We also report 5 patients from Gran Canaria, representing the largest known group of unrelated families sharing the same P406L mutation. CONCLUSIONS: Data analysis did not reveal a genotype-phenotype correlation, but stressed the need of early diagnosis: All patients improved the oculocutaneous lesions after dietary treatment but neurological symptoms prevailed. The discovery of founder mutations in isolated populations, and the benefits of early intervention, should increase diagnostic awareness in newborns.
Subject(s)
Founder Effect , Genetic Association Studies , Mutation , Phenotype , Tyrosinemias/diagnosis , Tyrosinemias/genetics , Adolescent , Age of Onset , Alleles , Child , Child, Preschool , Female , Genetic Loci , Genotype , Humans , Infant , Infant, Newborn , Male , Pedigree , Polymorphism, Single Nucleotide , Tyrosine Transaminase/genetics , Tyrosinemias/diet therapy , Young AdultABSTRACT
Neurocognitive impairment is a core feature of schizophrenia and is closely associated with functional outcome. The importance of cognitive assessment is broadly accepted today, and an easy-to-use, internationality validated cognitive assessment tool is needed by researchers and in daily clinical practice. The Brief Assessment of Cognition in Schizophrenia (BACS) has been validated in English, French, Japanese and Italian. It is as sensitive to cognitive dysfunction as a standard test battery, with the advantage of requiring less than 35minutes to complete. In our study, we tested the psychometric characteristics of a Spanish version of the BACS in 117 patients with schizophrenia-spectrum disorders and 36 healthy controls. All BACS cognitive subtests discriminated between patients and controls (P<.001), and the concurrent validity between the BACS and a traditional neuropsychological test battery was similar to that reported in other languages. We conclude that the BACS can facilitate the comparison of the cognitive performance of patients with schizophrenia in many different countries.
Subject(s)
Cognition Disorders/diagnosis , Neuropsychological Tests/standards , Psychotic Disorders/diagnosis , Schizophrenia/physiopathology , Schizophrenic Psychology , Adult , Case-Control Studies , Chronic Disease , Cognition Disorders/etiology , Cross-Cultural Comparison , Female , Humans , Male , Middle Aged , Psychometrics/statistics & numerical data , Psychotic Disorders/etiology , Reproducibility of Results , Schizophrenia/complications , Spain , Translating , Young AdultABSTRACT
A 22 year-old woman with tyrosinemia type I (HT1) married her first cousin who is heterozygous for the same FAH mutation for which the patient is homozygous. During her pregnancy she was treated with diet (prescribed tyrosine intake 300 mg/day), and nitisinone (60 mg/day). Median plasma tyrosine levels were 560 µmol/L (range: 375-838, n = 21) and nitisinone 51 µmol/L (range: 41-57, n = 3) during pregnancy. She gave birth to a clinically healthy girl affected with tyrosinemia type 1. Birth was normal (birth weight 2615 g) and the baby had normal liver function, normal plasma alpha-fetoprotein concentrations, low urinary excretion of phenolic acids and no detectable succinylacetone. At birth, the baby had hypertyrosinemia (860 µmol/L in blood cord) and nitisinone levels of 14 µmol/L. Following molecular confirmation of the diagnosis of HT1 specific treatment began on day 15 by which time she had detectable urinary succinylacetone.
Subject(s)
Hydrolases/genetics , Mutation , Tyrosinemias/genetics , Biomarkers/blood , Biomarkers/urine , Child Development , Consanguinity , Cyclohexanones/therapeutic use , DNA Mutational Analysis , Diet, Protein-Restricted , Female , Genetic Predisposition to Disease , Heptanoates/blood , Heptanoates/urine , Heredity , Heterozygote , Homozygote , Humans , Hydrolases/metabolism , Infant , Infant, Newborn , Live Birth , Nitrobenzoates/therapeutic use , Pedigree , Phenotype , Pregnancy , Tyrosine/blood , Tyrosinemias/diagnosis , Tyrosinemias/enzymology , Tyrosinemias/therapy , Young AdultABSTRACT
Lung cancer is a leading cause of death worldwide and, although some progress has been made in its treatment, the results remain poor. Better knowledge in tumour biology has allowed us to design anti-target drugs and incorporate them in the treatment of non-small-cell lung cancer (NSCLC). One of the most widely used targeted approaches in this type of tumour has been the inhibition of angiogenesis. Several strategies blocking the VEGF pathway, either at the ligand or recepor level, have been studied and developed. In this review, we present an up-to-date analysis of the current inhibitors of angiogenesis in the treatment of NSCLC (AU)
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