Homocysteine and methylmalonic acid in Phenylketonuria patients.

Hyperhomocysteinemia and vitamin B12 deficiency have been reported in patients with phenylketonuria. In this study, total homocysteine (tHcy) and methylmalonic acid (MMA) levels were analyzed in samples from 25 phenylketonuria (PKU) patients. Comparisons were made between pre- and post-treatment values (n= 3); on treatment values, between periods with high and normal/low phenylalanine (Phe) levels (n= 20); and in women before, during and after pregnancy (n= 3). THcy levels decreased after treating PKU with metabolic formula (p=0.014). Except for a pregnant woman before pregnancy, none of the patients had tHcy values above the normal range. In fact, tHcy was < 5 µmol/L in 34% of the samples. We observed a decrease in Phe, tHcy, and tyrosine levels during pregnancy. MMA levels did not differ significantly, with values remaining in the normal range. These data indicate that there was no B12 deficiency in patients who adhere to the diet. In conclusion, in PKU patients treated with metabolic formula, tHcy is frequently not elevated, remaining even in the lower normal range in some patients. Thus, clinical follow-up and adherence to dietary treatment are crucial to prevent B12 deficiency.

An adult with cystathionine beta-synthase deficiency, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, and deafness: A case report.

Massive sequencing platforms allow the identification of complex clinical phenotypes involving more than one autosomal recessive disorder. In this study, we report on an adult patient, born to a related couple (third degree cousins), referred for genetic evaluation due to ectopia lentis, deafness and previous diagnosis of juvenile idiopathic arthritis. He was biochemically diagnosed as having Classic Homocystinuria (HCU); Sanger sequencing of the CBS gene showed the genotype NM_000071.2(CBS):c.[833T>C];[833T>C], compatible with the diagnosis of pyridoxine-responsive HCU. As he also had symptoms not usually associated with HCU, exome sequencing was performed. In addition to the variants found in the Sanger sequencing, the following variants were identified: NM_001256317.1(TMPRSS3):c.[413C>A];[413C>A]; and the NM_005807.6(PRG4):c.[3756dup]:[3756dup], confirming the diagnosis of autosomal recessive nonsyndromic deafness and Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome (CACP), respectively. Genomic analysis allowed the refinement of the diagnosis of a complex case and improvement of the patient's treatment.

Potential use of other starch sources in the treatment of glycogen storage disease type Ia - an in vitro study.

BACKGROUND: Glycogen storage disease type Ia (GSD-Ia) is one of the most common hepatic GSD. Its treatment mainly consists of a diet including a high intake of slow-digestion carbohydrates such as raw cornstarch and the restriction of simple sugars. This enables the maintenance of euglycemia and prevents secondary metabolic disorders. Starch is a glucose polymer formed by amylose and amylopectin, which can be obtained from distinct sources. Although uncooked cornstarch has been successfully used in the treatment of GSD-Ia, it can lead to hyperglycemia and weight gain. in vitro andin vivo tests indicated that sweet manioc starch can be potentially used in the treatment of GSD-Ia. RESULTS: The moisture analysis revealed a variation from 10.3 to 12.8% in the sweet manioc starch samples, whereas the moisture content of uncooked cornstarch ranged from 7.3 to 11.1%. Quantifiable sugar was detected in 3/5 samples of sweet manioc starch and 1/3 samples of uncooked cornstarch. Notably, this uncooked cornstarch brand is widely employed in GSD-Ia treatment in Brazil. Products B and E had higher values of amylopectin and undetectable levels of sugars. A clinical trial is warranted to compare samples F and G and determine the impact of sugar trace in the same dietary source of starch. CONCLUSIONS: Collectively, the results demonstrated possible therapeutic alternatives for GSD-Ia in addition to traditional uncooked cornstarch.

Adequacy of Fatty Acids Consumption Among Individuals in Secondary Cardiovascular Prevention. / Adequação do Consumo de Ácidos Graxos entre Pacientes em Prevenção Cardiovascular Secundária.

BACKGROUND: Adhering to a diet adequate in macronutrients is crucial for the secondary prevention of cardiovascular diseases. OBJECTIVE: To assess the prevalence of adherence to recommendations for the consumption of dietary fatty acids for the prevention and treatment of cardiovascular diseases and to estimate whether the presence of certain cardiovascular risk factors would be associated with adherence. METHODS: Cross-sectional study using baseline data from 2,358 participants included in the "Brazilian Cardioprotective Nutritional Program Trial". Dietary intake and cardiovascular risk factors were assessed. Adequate intake of polyunsaturated fatty acids (PUFA) was considered as ≥10% of total daily energy intake; for monounsaturated fatty acids (MUFA), 20%; and for saturated fatty acids (SFA), <7% according to the Brazilian Society of Cardiology. A significance level of 5% was considered in the statistical analysis. RESULTS: No participant adhered to all recommendations simultaneously, and more than half (1,482 [62.9%]) did not adhere to any recommendation. Adherence exclusively to the SFA recommendation was the most prevalent, fulfilled by 659 (28%) participants, followed by adherence exclusively to the PUFA (178 [7.6%]) and MUFA (5 [0.2%]) recommendations. There was no association between the number of comorbidities and adherence to nutritional recommendations (p = 0.269). Participants from the Brazilian Northeast region showed a higher proportion of adherence to SFA consumption recommendations (38.42%) and lower adherence to PUFA intake (3.52%) (p <0.001) compared to other regions. CONCLUSIONS: Among the evaluated sample, there was low adherence to nutritional recommendations for dietary fatty acid consumption.

FUNDAMENTO: A adesão à uma alimentação adequada em macronutrientes é fundamental para a prevenção secundária de doenças cardiovasculares. OBJETIVO: Avaliar a prevalência de adesão às recomendações de consumo de ácidos graxos para prevenção e tratamento de doenças cardiovasculares, e estimar se a presença de determinados fatores de risco cardiovascular estaria associada à adesão. MÉTODOS: Estudo transversal com os dados de linha de base de 2358 participantes do estudo "Brazilian Cardioprotective Nutritional Program Trial". Dados de consumo alimentar, e fatores de risco cardiovascular foram avaliados. Foi considerada, de acordo com a Sociedade Brasileira de Cardiologia, uma ingestão adequada de ácidos graxos poli-insaturados (AGPI) ≥10% do consumo total de energia diária, para ácidos graxos monoinsaturados (AGM), 20% e para ácidos graxos saturados (AGS), <7%. Na análise estatística foi considerando nível de significância de 5%. RESULTADOS: Nenhum participante aderiu a todas as recomendações de forma simultânea e mais da metade (1482 [62,9%]) não aderiu a nenhuma recomendação. A adesão exclusivamente à recomendação de AGS foi a mais prevalente, sendo cumprida por 659 (28%) dos participantes, seguida da adesão exclusivamente à recomendação de AGP (178 [7,6%]) e de AGM (5 [0,2%]). Não houve associação entre o número de comorbidades e a adesão às recomendações nutricionais (p =0,269). Os participantes da região Nordeste do país apresentaram maior proporção de adesão às recomendações para consumo de AGS (38,42%), e menor para ingestão de AGPI (3,52%) (p <0,001) em comparação às demais. CONCLUSÕES: Na amostra avaliada, evidenciou-se baixa adesão às recomendações nutricionais para consumo de ácidos graxos.

Adequação do consumo de ácidos graxos entre pacientes em prevenção cardiovascular secundária / Adequacy of Fatty Acids Consumption Among Individuals in Secondary Cardiovascular Prevention

FUNDAMENTO: A adesão à uma alimentação adequada em macronutrientes é fundamental para a prevenção secundária de doenças cardiovasculares. OBJETIVO: Avaliar a prevalência de adesão às recomendações de consumo de ácidos graxos para prevenção e tratamento de doenças cardiovasculares, e estimar se a presença de determinados fatores de risco cardiovascular estaria associada à adesão. MÉTODOS: Estudo transversal com os dados de linha de base de 2358 participantes do estudo "Brazilian Cardioprotective Nutritional Program Trial". Dados de consumo alimentar, e fatores de risco cardiovascular foram avaliados. Foi considerada, de acordo com a Sociedade Brasileira de Cardiologia, uma ingestão adequada de ácidos graxos poli-insaturados (AGPI) ≥10% do consumo total de energia diária, para ácidos graxos monoinsaturados (AGM), 20% e para ácidos graxos saturados (AGS), <7%. Na análise estatística foi considerando nível de significância de 5%. RESULTADOS: Nenhum participante aderiu a todas as recomendações de forma simultânea e mais da metade (1482 [62,9%]) não aderiu a nenhuma recomendação. A adesão exclusivamente à recomendação de AGS foi a mais prevalente, sendo cumprida por 659 (28%) dos participantes, seguida da adesão exclusivamente à recomendação de AGP (178 [7,6%]) e de AGM (5 [0,2%]). Não houve associação entre o número de comorbidades e a adesão às recomendações nutricionais (p =0,269). Os participantes da região Nordeste do país apresentaram maior proporção de adesão às recomendações para consumo de AGS (38,42%), e menor para ingestão de AGPI (3,52%) (p <0,001) em comparação às demais. CONCLUSÕES: Na amostra avaliada, evidenciou-se baixa adesão às recomendações nutricionais para consumo de ácidos graxos.

Brazilian Food Reference Guide for Phenylalanine Content: A Study Based on the Perception of PKU Patients and Health Providers

Abstract The mainstay of management of phenylketonuria (PKU) is restriction of dietary phenylalanine (Phe) intake. The present study sought to assess the perception and understanding of health care providers and lay users (patients/family members/caregivers) regarding the national reference database for checking the Phe content of foods, provided by the Brazilian Health Regulatory Agency (Anvisa), whose data are presented in the Table of Phenylalanine Content of Foods (TCFA-Anvisa) and recently in the Phenylalanine Content of Foods Dashboard (PCCFA-Anvisa); and to identify factors which interfere with the usability of these resources. Two online questionnaires, one for providers (n=33) and another for lay users (n=194), were used to collect sociodemographic information, knowledge about dietary management of PKU, sources of information about the Phe content of foods, and perception and understanding of the Anvisa tools. TCFA-Anvisa and PCCFA-Anvisa were not used as main sources of information by either group. Among the participants who had used these tools (15 providers;35 lay users), most considered the PCCFA-Anvisa to be superior or partially superior to the TCFA-Anvisa. The main limitations reported were related to layout and limited variety of foods. We suggest that the limitations identified in this study be considered for future improvement of these resources.

Three Main Causes of Homocystinuria: CBS, cblC and MTHFR Deficiency. What do they Have in Common?

Abstract Genetic homocystinurias are a group of inborn errors of metabolism that result in the massive excretion of homocysteine (Hcy) in the urine due to Hcy accumulation in the body, usually causing neurological and cardiovascular complications. The three most frequent causes are classical homocystinuria [deficiency of cystathionine beta-synthase (CBS)], methylmalonic aciduria with homocystinuria, cblC type (cblC deficiency) and severe methylenetetrahydrofolate reductase (MTHFR) deficiency. In this review, we highlight the similarities and differences among these disorders. Briefly, their joint manifestation is the accumulation of tHcy, however, the other sulfur amino acids show various and even invers profiles. Vascular disease, developmental delay and seizures are found in all homocystinurias, nevertheless, the complications of CNS differ in a wide variety of presentations and severities and are apparently less pronounced in CBS deficiency. Moreover, patients with remethylation defects typically do not present ectopia lentis and bone disturbances, tall stature and osteoporosis. Whereas hematological alterations, such as megaloblastic anemia, thrombocytopenia neutropenia and life-threatening microangiopathy, are specific findings of cblC deficiency.

Diagnosis and Management of Classica Homocystinuria in Brazil: A Summary of 72 Late-Diagnosed Patients

Abstract This study described a broad clinical characterization of classical homocystinuria (HCU) in Brazil. This was a cross-sectional, observational study including clinical and biochemical data from 72 patients (60 families) from Brazil (South, n = 13; Southeast, n = 37; Northeast, n = 8; North, n = 1; and Midwest, n = 1). Parental consanguinity was reported in 42% of families. Ocular manifestations were the earliest detected symptom (53% of cases), the main reason for diagnostic suspicion (63% of cases), and the most prevalent manifestation at diagnosis (67% of cases). Pyridoxine responsiveness was observed in 14% of patients. Only 22% of nonresponsive patients on treatment had total homocysteine levels <100 mmol/L. Most commonly used treatment strategies were pyridoxine (93% of patients), folic acid (90%), betaine (74%), vitamin B12 (27%), and low-methionine diet + metabolic formula (17%). Most patients diagnosed with HCU in Brazil are late diagnosed, express a severe phenotype, and poor metabolic control. Milder forms of HCU are likely underrepresented due to underdiagnosis.