RESUMO
The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment. They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging. Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought. The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients. The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%). Based on their serum transferrin isoform profile, 18 were classified as CDG-I and 7 as CDG-II. Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4). Overall, 27 variants were identified, 12 of which are novel. The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
Assuntos
Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Fosfotransferases (Fosfomutases)/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , EspanhaRESUMO
PURPOSE: Salts of phenylacetic acid (PAA) and phenylbutyric acid (PBA) have been used for nitrogen elimination as a treatment for hyperammonaemia caused by urea cycle disorders (UCD). A new analytical method for PBA measurement in urine which helps to evaluate the drug adherence has been implemented. METHODS: Urine specimens from UCD patients receiving PBA were analysed by tandem mass spectrometry to measure urine phenylacetylglutamine (PAGln). Some clinical and biochemical data for each patient were collected. RESULTS: Our study included 87 samples from 40 UCD patients. The PAGln levels did not correlate with height, weight or age. However, the PAGln values showed correlation with PBA dose (râ¯=â¯0.383, Pâ¯=â¯0.015). Plasma glutamine and ammonia levels presented a positive correlation (râ¯=â¯0.537, Pâ¯<â¯0.001). The stability for PAGln in urine was determined at different storage temperatures. CONCLUSIONS: We have developed a simple method for the determination of PAGln in urine, which acts as useful biomarker of effective drug delivery. PAGln in urine is stable at room temperature at least for 15 days, and for several months when frozen at -20⯰C. This procedure is useful for the optimization and monitorization of the drug dose allowing the use of spot urine samples.
Assuntos
Benzoatos/farmacocinética , Monitoramento de Medicamentos/métodos , Glutamina/análogos & derivados , Fenilbutiratos/farmacocinética , Distúrbios Congênitos do Ciclo da Ureia/tratamento farmacológico , Adolescente , Adulto , Benzoatos/uso terapêutico , Biomarcadores/urina , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Glutamina/metabolismo , Glutamina/urina , Humanos , Lactente , Recém-Nascido , Masculino , Adesão à Medicação , Fenilbutiratos/uso terapêutico , Espectrometria de Massas em Tandem/métodos , Distúrbios Congênitos do Ciclo da Ureia/urina , Adulto JovemRESUMO
No disponible
Assuntos
Humanos , Criança , Calcifediol/sangue , Receptores de Calcitriol/metabolismo , Deficiência de Vitamina D/epidemiologiaRESUMO
BACKGROUND: Advances in the diagnosis and treatment of urea cycle disorders (UCDs) have led to a higher survival rate. The purpose of this study is to describe the characteristics of patients with urea cycle disorders in Spain. METHODS: Observational, cross-sectional and multicenter study. Clinical, biochemical and genetic data were collected from patients with UCDs, treated in the metabolic diseases centers in Spain between February 2012 and February 2013, covering the entire Spanish population. Heterozygous mothers of patients with OTC deficiency were only included if they were on treatment due to being symptomatic or having biochemistry abnormalities. RESULTS: 104 patients from 98 families were included. Ornithine transcarbamylase deficiency was the most frequent condition (64.4%) (61.2% female) followed by type 1 citrullinemia (21.1%) and argininosuccinic aciduria (9.6%). Only 13 patients (12.5%) were diagnosed in a pre-symptomatic state. 63% of the cases presented with type intoxication encephalopathy. The median ammonia level at onset was 298 µmol/L (169-615). The genotype of 75 patients is known, with 18 new mutations having been described. During the data collection period four patients died, three of them in the early days of life. The median current age is 9.96 years (5.29-18), with 25 patients over 18 years of age. Anthropometric data, expressed as median and z-score for the Spanish population is shown. 52.5% of the cases present neurological sequelae, which have been linked to the type of disease, neonatal onset, hepatic failure at diagnosis and ammonia values at diagnosis. 93 patients are following a protein restrictive diet, 0.84 g/kg/day (0.67-1.10), 50 are receiving essential amino acid supplements, 0.25 g/kg/day (0.20-0.45), 58 arginine, 156 mg/kg/day (109-305) and 45 citrulline, 150 mg/kg/day (105-199). 65 patients are being treated with drugs: 4 with sodium benzoate, 50 with sodium phenylbutyrate, 10 with both drugs and 1 with carglumic acid. CONCLUSIONS: Studies like this make it possible to analyze the frequency, natural history and clinical practices in the area of rare diseases, with the purpose of knowing the needs of the patients and thus planning their care.
Assuntos
Distúrbios Congênitos do Ciclo da Ureia/diagnóstico , Distúrbios Congênitos do Ciclo da Ureia/epidemiologia , Distúrbios Congênitos do Ciclo da Ureia/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Espanha/epidemiologia , Adulto JovemRESUMO
No disponible