Analysis of body composition and nutritional status in Brazilian phenylketonuria patients

BACKGROUND: Phenylketonuria (PKU) is characterized by phenylalanine (Phe) accumulation to toxic levels due to the low activity of phenylalanine-hydroxylase. PKU patients must follow a Phe-restricted diet, which may put them in risk of nutritional disturbances. Therefore, we aimed to characterize body composition parameters and nutritional status in Brazilian PKU patients also considering their metabolic control.METHODS: Twenty-seven treated PKU patients older than 5 years, and 27 age- and gender-matched controls, were analyzed for anthropometric features and body composition by bioelectrical impedance (BIA). Patients' metabolic control was assessed by historical Phe levels.RESULTS: There was no effect of PKU type, time of diagnosis, or metabolic control for any analyzed parameter. About 75% of patients and controls were eutrophic, according to their BMI values. There were no difference between groups regarding body composition and other BIA-derived parameters.CONCLUSIONS: Brazilian PKU patients do not show differences in body composition and nutritional status in comparison with controls, regardless metabolic control. Although similar to controls, PKU patients may be in risk of disturbed nutritional and metabolic markers as seen for the general population.</p

Glycogen storage diseases : twenty‐seven new variants in a cohort of 125 patients

Hepatic glycogen storage diseases (GSDs) are a group of rare genetic disorders in which glycogen cannot be metabolized to glucose in the liver because of enzyme deficiencies along the glycogenolytic pathway. GSDs are well‐recognized diseases that can occur without the full spectrum, and with overlapping in symptoms.We analyzed a cohort of 125 patients with suspected hepatic GSD through a next‐generation sequencing (NGS) gene panel in Ion Torrent platform. New variants were analyzed by pathogenicity prediction tools.Twenty‐seven new variants predicted as pathogenic were found between 63 variants identified. The most frequent GSD was type Ia (n = 53), followed by Ib (n = 23). The most frequent variants were p.Arg83Cys (39 alleles) and p.Gln347* (14 alleles) in G6PC gene, and p.Leu348Valfs (21 alleles) in SLC37A4 gene.The study presents the largest cohort ever analyzed in Brazilian patients with hepatic glycogenosis. We determined the clinical utility of NGS for diagnosis. The molecular diagnosis of hepatic GSDs enables the characterization of diseases with similar clinical symptoms, avoiding hepatic biopsy and having faster results.711CNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoNão te

Body composition in patients with classical homocystinuria: body mass relates to homocysteine and choline metabolism

Introduction: Classical homocystinuria is a rare genetic disease caused by cystathionine beta-synthase deficiency, resulting in homocysteine accumulation. Growing evidence suggests that reduced fat mass in patients with classical homocystinuria may be associated with alterations in choline and homocysteine pathways. This study aimed to evaluate the body composition of patients with classical homocystinuria, identifying changes in body fat percentage and correlating findings with biochemical markers of homocysteine and choline pathways, lipoprotein levels and bone mineral density (BMD) T-scores.Methods: Nine patients with classical homocystinuria were included in the study. Levels of homocysteine, methionine, cysteine, choline, betaine, dimethylglycine and ethanolamine were determined. Body composition was assessed by bioelectrical impedance analysis (BIA) in patients and in 18 controls. Data on the last BMD measurement and lipoprotein profile were obtained from medical records.Results: of 9 patients, 4 (44%) had a low body fat percentage, but no statistically significant differences were found between patients and controls. Homocysteine and methionine levels were negatively correlated with body mass index (BMI), while cysteine showed a positive correlation with BMI (p < 0.05). There was a trend between total choline levels and body fat percentage (r = 0.439, p = 0.07). HDL cholesterol correlated with choline and ethanolamine levels (r = 0.757, p = 0.049; r = 0.847, p = 0.016, respectively), and total cholesterol also correlated with choline levels (r = 0.775, p = 0.041). There was no association between BMD T-scores and body composition.Conclusions: These results suggest that reduced fat mass is common in patients with classical homocystinuria, and that alterations in homocysteine and choline pathways affect body mass and lipid metabolism. (C) 2014 Elsevier B.V. All rights reserved.Research Incentive Fund (Fundo de Incentivo a Pesquisa, FIPE) of HCPAPRONEM/FAPERGSConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Rio Grande do Sul, Postgrad Program Genet & Mol Biol, Porto Alegre, RS, BrazilHosp Clin Porto Alegre, BRAIN Lab Basic Res & Adv Invest Neurosci, BR-90035003 Porto Alegre, RS, BrazilHosp Clin Porto Alegre, Med Genet Serv, BR-90035003 Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Reference Ctr Inborn Errors Metab, São Paulo, BrazilUniv Fed Rio Grande do Sul, Dept Physiol, Hosp Clin Porto Alegre, Gynecol Endocrinol Unit,Div Endocrinol, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Food & Nutr Res Ctr, Hosp Clin Porto Alegre, Porto Alegre, RS, BrazilRobert Debre Hosp, AP HP, Biochem Hormonol Lab, Paris, FranceUniv Med Ctr Freiburg, Dept Gen Pediat, Lab Clin Biochem & Metab, Freiburg, GermanyUniversidade Federal de São Paulo, Reference Ctr Inborn Errors Metab, São Paulo, BrazilResearch Incentive Fund (Fundo de Incentivo a Pesquisa, FIPE) of HCPA: 11-0386PRONEM/FAPERGS: 11/2043-0CNPq: 308816/2013-7CNPq: 301742/2010-3CAPES: 12785-11Web of Scienc

A triple-blinded crossover study to evaluate the short-term safety of sweet manioc starch for the treatment of glycogen storage disease type Ia

BACKGROUND: Glycogen storage disease type 1a (GSD Ia) is characterized by severe fasting hypoglycemia. The clinical management includes the administration of uncooked cornstarch (UCCS). Although such a diet approach is effective in achieving euglycemia, its impact on the quality of life of patients should be considered. In vitro analyses suggest a longer release of glucose when using sweet manioc starch (SMS). METHODS: We compared the efficacy and safety of the administration of SMS and UCCS during a short-fasting challenge in patients with GSD Ia in a randomized, triple-blind, phase I/II, cross-over study. GSD Ia patients aged ≥ 16 years and treated with UCCS were enrolled. Participants were hospitalized for two consecutive nights, receiving UCCS or SMS in each night. After the administration of the starches, glucose, lactate and insulin levels were measured in 1-h interval throughout the hospitalization period. The procedures were interrupted after 10 h of fasting or in a hypoglycemic episode ( 25 kg/m(2)) participated in the study. The average fasting period was 8.2 ± 2.0 h for SMS and 7.7 ± 2.3 h for UCCS (p = 0.04). SMS maintained euglycemia for a greater period over UCCS. Increased lactate concentrations were detected even in absence of hypoglycemia, not being influenced by the different starches investigated (p = 0.17). No significant difference was found in total cholesterol, HDL, triglycerides and uric acid levels in both arms. None of the patients showed severe adverse events. CONCLUSIONS: SMS appears to be non-inferior to UCCS in the maintenance of euglycemia, thus emerging as a promising alternative to the treatment of GSD Ia

Glycogen storage disease type I: clinical and laboratory profile

OBJECTIVES: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. METHODS: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. RESULTS: Twenty-one patients were included (median age 10 years, range 1-25 years), all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1-132 months), and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008). CONCLUSIONS: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients

Evaluation of the frequency of non-motor symptoms of Parkinson’s disease in adult patients with Gaucher disease type 1

Abstract Background Gaucher disease (GD) is caused by deficiency of beta-glucocerebrosidase (GCase) due to biallelic variations in the GBA1 gene. Parkinson’s disease (PD) is the second most common neurodegenerative condition. The classic motor symptoms of PD may be preceded by many non-motor symptoms (NMS), which include hyposmia, rapid eye movement (REM) sleep behavior disorder, constipation, cognitive impairment, and depression. Population studies have identified mutations in GBA1 as the main risk factor for idiopathic PD. The present study sought to evaluate the prevalence of NMS in a cohort of patients with GD type 1 from Southern Brazil. Methodology This is an observational, cross-sectional study, with a convenience sampling strategy. Cognition was evaluated by the Montreal Cognitive assessment (MoCa), daytime sleepiness by the Epworth Scale, depression by the Beck Inventory, constipation by the Unified Multiple System Atrophy Rating Scale, and REM sleep behavior disorder by the Single-Question Screen; hyposmia by the Sniffin’ Sticks. Motor symptoms were assessed with part III of the Unified Parkinson’s Disease Rating Scale. All patients were also genotyped for the GBA1 3′-UTR SNP (rs708606). Results Twenty-three patients (female = 13; on enzyme replacement therapy = 21, substrate reduction therapy = 2) with a mean age of 41.45 ± 15.3 years (range, 22–67) were included. Eight patients were found to be heterozygous for the 3′-UTR SNP (rs708606). Fourteen patients (8 over age 40 years) presented at least one NMS; daytime sleepiness was the most frequent (n = 10). Two patients (aged 63 and 64, respectively) also presented motor symptoms, probably drug-related. Conclusions NMS were prevalent in this cohort. We highlight the importance of a multidisciplinary follow-up focusing on earlier diagnosis of PD, especially for patients with GD type 1 over the age of 40