Diet therapy and metabolic control among Chilean adults with a neonatal diagnosis of Phenylketonuria

Abstract Phenylketonuria (PKU) is an autosomal recessive defect affecting the metabolic pathway of phenylalanine (Phe), causing hyperphenylalaninemia and neurotoxicity. Diagnosis must occur in the neonatal period and treatment should begin as early as possible. Evidence implies that treatment adherence declines as age advances. The aim was to describe the diet of a subgroup of Chilean adults with PKU currently in follow-up. Fifty-three subjects (49% women) followed up between January 2021 to April 2023 were considered. The concentration of Phe (PheC) in dried blood spots measured by fluorometry and 24-hour dietary recalls were analyzed. The median PheC of the sample was 438µmol/L (interquartile range(IQR):351-585µmol/L). A protein intake of 1.35±0.3 gr/Kg/d was observed of which 87% came from the protein substitute without Phe. Participants had a median Phe intake of 459mg/d (IQR:327-976) and 13.1g/d of fiber intake. Most participants, 51% and 92% reported consuming fruits and vegetables, respectively, and 32% consumed Low-Protein foods. Regarding micronutrients, all participants exceeded 90% adequacy according to recommendations. For vitamin-D and vitamin-B12, 100% is provided by the protein substitute. According to our results, it is mandatory to establish transition programs toward adulthood, to constantly maintain good metabolic control, and to adapt diet therapy to their new lifestyle.

Uso de bebidas energizantes y síntomas de insomnio en estudiantes de medicina de una universidad peruana / Use of energy drinks and insomnia symptoms in medical students from a Peruvian university

OBJETIVO: Determinar la asociación entre el consumo de bebidas energizantes y síntomas de insomnio en estudiantes de medicina de una universidad en Lima, Perú. MATERIALES Y MÉTODO: El tipo de estudio realizado es transversal analítico. La población objetivo fueron los estudiantes de medicina de una universidad peruana ubicada en Lima sur de segundo y quinto año. Hubo 289 participantes en el estudio. Se utilizó una encuesta compuesta por un cuestionario sobre el consumo de bebidas energizantes y el Insomnia Severity Index, del cual se determinó un punto de corte de 15 para considerar la presencia de síntomas de insomnio. El análisis multivariado crudo y ajustado se realizó usando la regresión de Poisson con varianza robusta ajustado para sexo, edad, consumo de café, y antecedente de ansiedad y depresión, para obtener el PR (Razón de Prevalencias) con un intervalo de confianza de 95%. RESULTADOS Y DISCUSIÓN: La prevalencia de síntomas de insomnio en la muestra estudiada fue de 21,80%, mientras que la de consumo de bebidas energizantes fue de 39,45%. Se encontró asociación significativa (p=0,008) entre el consumo de este tipo de bebidas y la presencia de síntomas de insomnio. Además, se encontró que los estudiantes que consumen bebidas energizantes tuvieron 1,78 veces más probabilidad de presentar síntomas de insomnio (IC95%: 1,13-2,82), en comparación con los que no consumieron bebidas energizantes (p=0,013). CONCLUSIONES: Existe asociación entre el consumo de bebidas energizantes y síntomas de insomnio.

OBJECTIVE: To determine the association between the consumption of energy drinks and symptoms of insomnia in medical students of a university in Lima, Peru. Materials and METHODS: This study is cross-sectional analytical. The target population was the second-and fifth-year medical students of a private Peruvian university in southern Lima. There were 289 participants in this study. For this study, a survey composed of a questionnaire about the consumption of energy drinks and the Insomnia Severity Index were used, from which a cut-off point of 15 was determined to consider the presence of insomnia symptoms. The multivariate crude and adjusted analysis were done with Poisson regression with robust variance adjusted for sex, age, coffee consumption, previous diagnosis of depression and previous diagnosis of anxiety; to calculate the PR (Prevalence Ratio) with a 95% CI. RESULTS AND DISCUSSION: The prevalence of insomnia symptoms in the sample studied was 21,80%, while the consumption of energy drinks was 39,45%. A significant association was found (p = 0.008) between the consumption of this type of drinks and the presence of insomnia symptoms. In addition, it was found that students who consumed energy drinks were 1,78 times more likely to have symptoms of insomnia (95% CI: 1,13-2,82), compared to those who did not consume energy drinks (p=<0,013). CONCLUSIONS: There is an association between the consumption of energy drinks and symptoms of insomnia.

Molecular basis of various forms of maple syrup urine disease in Chilean patients.

BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1ß, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients. METHODS: This manuscript describes a cross-sectional study of 18 MSUD patients carried out using PCR and DNA sequencing. RESULTS: Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients. CONCLUSION: If MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype-phenotype relationships more efficiently.

25 Hydroxy Vitamin D Level, Bone Health, Vitamin D and Calcium Intake in Chilean Patients with Phenylketonuria and Hyperphenylalaninemias

Abstract It has been shown that there is a decrease in the concentrations of 25 hydroxyvitamin D (25-OHD) and bone mineral density (BMD) in patients with phenylketonuria (PKU) in their follow-up. Our objective was to determine concentrations of 25-OHD in subjects with PKU and hyperphenylalaninemia (HPA). Transversal analytical study considered three groups: G1-PKU with neonatal diagnosis and formula intake without Phe; G2-HPA, without specific treatment and G3-C control group. Sixteen patients per group (aged 6-23) were included. Levels of 25-OHD, lumbar spine (L2-L4), femur and total BMD, intact parathormone (PTH) and vitamin D (VitD) and calcium intake were calculated. The Kruskal-Wallis statistical test was applied (p-value<0,05). Significant differences were detected in concentrations of 25-OHD between G1-PKU and G2-HPA (38.9 ng/mL; 28 ng/mL, respectively) (NV: >30 ng/mL). G1-PKU had a higher intake of VitD, with differences among groups. There were no significant differences among groups in relation to BMD and intact PTH. In conclusion, G1-PKU under treatment and with good adherence, does not present VitD deficiency and no BMD alterations are observed. In contrast, G2-HPA had a lower intake of VitD and decreased 25-OHD concentrations which could affect the bone architecture in the long term. Further studies on the G2-HPA are suggested.

Update on Dietary Compliance, Nutritional Status, and Neuropsychological Functioning in the Chilean Phenylketonuria cohort

Abstract Since 1992, Chile has had a Newborn Screening Program for Phenylketonuria (PKU), which currently has an incidence of 1:18,916 newborns. The objective of the current study was to describe the 2020 follow up of the Chilean PKU cohort. The variables analyzed were: nutritional status, dietary compliance and neuropsychological functioning. We conducted a descriptive cross-sectional statistical analysis. The 271 subjects with PKU had an average age of diagnosis of 17±8 days and a phenylalanine (Phe) level of 1122±546 umol/L. Approximately 80% of protein requirement came from a protein substitute. For those <18 years of age, 80% had good dietary compliance with Phe level between 120-360 umol/L and those >18 years had a median of 522 umol/L (95%CI 468 - 636). Forty-four percent of the active PKU cohort had overweight/obesity. Eighty-five percent of the cohort >4 years of age had a normal intelligence quotient (IQ) (score 80-120). We observed a negative correlation (p <0.001; 95% CI: - 0.5, -0.2) between IQ score and Phe level. The Chilean protocol and protein substitute subsidy for life, together with the follow-up and continuous education carried out by the clinical team has encouraged compliance.

Characterization of Phenyalanine Hydroxylase Gene Mutations in Chilean PKU Patients.

Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive disease, caused by mutations in the Phenylalanine Hydroxylase (PAH) gene situated in chromosome 12q22-q24.2. This gene has 13 exons. To date, 991 mutations have been described. The genotype is one of the main factors that determine the phenotype of this disease. OBJECTIVE: Characterize PKU genotype and phenotype seen in Chilean PKU patients. METHODS: We studied the PAH gene by restriction fragment length polymorphism (RFLP) and/or sequencing techniques to identify pathogenic mutations in 71 PKU subjects. We classified the phenotype according to Guldberg predicted value. RESULTS: We identified 26 different mutations in 134 of the 142 alleles studied (94.4%), 88.7% of the subjects had biallelic pathogenic mutations while 11.3% had only one pathogenic mutation identified. Compound heterozygous represented 85.9% of the cases. Exon 7 included the majority of mutations (26.9%) and 50% of mutations were missense. The most frequent mutations were c.1066-11G > A, c.442-?_509+?del and p.Val388Met. The majority of subjects (52.3%) had the classic phenotype. CONCLUSIONS: The most frequent mutations in our Chilean PKU population were p.Val388Met, c.442?_509+?del and c.1066-11G > A. It is possible to predict phenotype by detecting the genotype, and use this information to determine disease prognosis and adjust patient's medical and nutritional management accordingly.

Past, present and future of newborn screening in Chile.

The history of the Newborn Screening Program in Chile begins in 1984, when a pilot plan was developed that demonstrated the feasibility of its implementation. In 1992, the Ministry of Health started a national newborn screening program for phenylketonuria (PKU) and congenital hypothyroidism (CH), and in 1998, this was extended to the entire country. Throughout this period, a total of 2,478,123 newborns (NB) have been analyzed, obtaining initial coverage of 48.8%, which was later increased to 87.7%, and at present it is at 98.7% of all NB of our country. During this period, 131 cases with PKU have been diagnosed, resulting in an incidence of 1:18,916 NB, an average age of diagnosis of 18 ± 10.2 days and average phenylalanine level of 19,9 ± 8.8 mg/dl. In relation to CH, 783 cases have been confirmed, arriving at an incidence of 1:3,163 NB, with average age of diagnosis of 12.5 ± 6.9 days. Due to the good results of the program, the government is evaluating the initiation of an extended pilot program, to introduce other pathologies.

Del Xq23 in a mosaic Turner female: molecular and cytogenetic studies.

We report a Turner patient aged 22 years with a 45,X/46,X,del(X)(q23) karyotype. Late replication studies showed preferential inactivation of the deleted X chromosome; FISH studies with a probe for total human telomeres showed hybridisation signal in the telomeres on both the normal and the deleted X chromosomes. Microsatellite analysis in the proposita and her family permitted us to conclude to the maternal origin of the deleted X chromosome, and to detect using the marker DXS1106 (Xq22) a probable meiotic recombination event above the breakage point suggesting that the deletion occurred underneath this point. The mild Turner stigmata may be explained by the 45,X cell line, and the gonadal dysgenesis probably by a partial deletion of the gonadal dysgenesis region Xq13-q23 (excluding Xq22).

Molecular characterization of phenylalanine hydroxylase deficiency in Chile. Mutations in brief no. 243. Online.

Both the haplotype distribution and the mutational spectrum of the phenylalanine hydroxylase (PAH) gene has been defined for the Chilean phenylketonuria (PKU) population. Mutation analysis was performed using a combined approach of screening for common European and Oriental mutations and application of the DGGE scanning method in the remaining uncharacterized alleles. A total of 16 different mutations have been identified, including two novel ones, Q232X and IVS11nt5. The most frequent mutations were IVS10nt-11 and V388M present both in the 13% of the mutant chromosomes. The rest of the mutations are rare. The haplotype association including VNTR and STR alleles, was examined to investigated the origin and distribution of PAH alleles in Chile. Our results are consistent with Southern Europeans as the major source of PAH mutations in Latin America. However, we have also detected mutations from East and Central Europe, such IVS12nt1, R408W and R252W. It is clear that the PKU mutation present in each Latin American country varies with the demographic profile and specific mutation scanning is necessary in each population both for diagnostic and prognostic purposes. The correlation between the genotypes and the phenotypes is consistent with the emerging pattern of mutation severity deduced from previous studies in related populations.

[Early diagnosis of phenylketonuria. Follow up of 2 cases]. / Diagnostico precoz de fenilquetonuria. Seguimiento de 2 casos.

A screening program for the early diagnosis of phenylketonuria was initiated 24 months ago in the Servicio de Salud Metropolitano Central. Since then, 2 cases with phenylketonuria have been early diagnosed. These patients started their nutritional treatment, consisting of a phenylalanine restricted diet at 14 and 17 days of age. The children are submitted to periodic medical, anthropometric, neurologic, biochemical and psychometric analysis. With a strict control they maintain phenylalanine plasma levels between 2 and 6 mg%. Both patients have a normal psychomotor development at 4.5 and 6.5 months of age and an anthropometric development at p50 of NCHS.

Tratamiento quirúrgico de la úlcera gástrica: experiencia de 12 años / Surgical treatment of gastric ulcer: 12 years experience

El propósito de este estudio fue revisar los resultados quirúrgicos inmediatos en la cirugía de la úlcera gástrica durante 12 años en nuestro Hospital. Se hace notar el alto porcentaje de úlceras subcardiales, y el tipo de cirugía empleada. Se destaca, los buenos resultados, con mortalidad de 0,68%, a pesar de incluir la cirugía de urgencia

[Program of neonatal screening for phenylketonuria]. / Programa de rastreo neonatal de fenilquetonuria.

A screening program for phenylketonuria in newborn infants that is being carried out at one of the Metropolitan Health Services at Santiago, Chile for the last 17 months, using the Guthrie test, is described. During this period 15,214 blood samples have been analyzed, which represented 94.4% coverage for beneficiary newborn infants. Two cases of transient hyperphenylalaninemia, one patient with benign hyperphenylalaninemia, and one infant with classical phenylketonuria have been thus identified. In this last child nutritional management was started at 13 days of life. Screening programs for early detection of phenylketonuria in Chile seem convenient, feasible and reliable.

Efecto de la razón energía/proteína de la dieta sobre la composición nutricional y la aceptabilidad de la porción comestible del broiler / Effect of the dietary energy/protein ratio on the nutritional composition and acceptance of the edible part of broiler chicken

Se alimentaron pollos de carne (broiler) comerciales durante diferentes períodos: 7-14 días de edad (ex-1); 7-21 (Ex-2); y 21-35 (Ex-3) respectivamente, con una dieta cuya razón energía proteína era estrecha, el resto del ensayo, las aves fueron alimentadas con las mismas dietas que recibía el grupo control. El propósito del presente trabajo fue evaluar el efecto del manejo alimentario señalado sobre la composición de la carcasa y la aceptabilidad de la porción comestible del pollo de carne. Los resultados, a los 49 días de edad, pusieron en evidencia que el peso vivo final fue menor (p < 0,001), en los tratamientos ensayados con respecto del control. Por otra parte, hubo una reducción del depósito graso abdominal en las carcasas de los grupos experimentales, aunque no significativo, al compararlo con el control y un menor contenido de lípidos (p < 0,065) en la porción comestible de Ex-2 y Ex-3. Finalmente, la evaluación sensorial efectuada señaló ausencia de diferencias significativas entre los tratamientos. La información reunida plantea la necesidad de seguir buscando la mejor estrategia nutricional para lograr un producto de consumo que sea apropiado para el usuario final y al mismo tiempo, permita una rentabilidad satisfactoria a los avicultores

Penicilina clemizol y penicilina sódica en neumopatías agudas infecciosas en los niños / Clemizol penicillin and sodic penicillin in acute infectious pneumopathies in children

Objetivo: Evaluar utilidad de Penicilina-Clemizol (PNC-Clemizol) en el tratamiento de neumonias y bronconeumonias bacterianas en los niños, comparado con Penicilina Sódica (PNC-Sódica). Diseño: Estudio randomizado con una duración de 8 días de tratamiento. Lugar: Pacientes hospitalizados en el Servicio de Pediatría, Hospital Roy H. Glover, Chuquicamata. Pacientes: 46 pacientes distribuidos en forma randomizada en 2 grupos de 23 pacientes cada uno; un grupo tratado con PNC-Clemizol y el otro con PNC-Sódica. Intervenciones: El grupo PNC-Clemizol, recibió PNC-Clemizol Forte 100.000 U x Kg. en una dosis IM en el 1er. día y luego PNC-Clemizol 50.000 U x Kg x día IM. por 7 días; el grupo PNC-Sódica recibió 100.000 x Kg x día IM de PNC-Sódica fraccionada cada 8 horas, por 8 días. Resultado final: Mejoría y evolución favorable de las neumonias y bronconeumonias tratadas en ambos grupos de niños. Mediciones y resultados: Los siguientes parámetros fueron analizados de acuerdo a la mejoría en días: temperatura, tos, dificultad respiratoria, síndrome de condensación y tiempo de uso de Croupette. En los parámetros evaluados no hubo diferencias significativas entre ambos grupos, excepto para el síntoma temperatura, que disminuyó más rápido en el grupo PNC-Clemizol (p < 0,05). Conclusiones: Ambos medicamentos son igualmente útiles en el tratamiento de neumopatías agudas infecciosas en los niños, siendo mejor tolerado el tratamiento en el grupo PNC-Clemizol

Trimetoprim versus cotrimoxazol en el tratamiento de la infección urinaria en niños / Trimethoprim versus cotrimoxazole in the treatment of urinary infection in children

Se presenta estudio comparativo de tratamiento de infección urinaria en 60 pacientes pediátricos, distribuidos en forma randomizada en 2 grupos de 30 pacientes cada uno. Grupo A, tratado con trimetroprim (TMP) puro 6 mg/kg/día, en dos dosis y grupo B, tratado con cotrimoxazole (CTM) en dosis de 6 mg/kg/día de TMP + 30 mg/kg/día Sulfametoxazol, también en dos dosis. Ambos grupos tratados por 10 días. Se efectuó evaluación clínica y bacteriológica al cuarto y treintavo día, después de terminado el tratamiento. La distribución por sexo, edad, germen encontrado, técnica de toma de muestra y los síntomas predominantes fueron similares en ambos grupos. En el grupo tratado con TMP, se obtuvo resultado excelente en 29 casos (97%), bueno en un caso, sin fracaso al tratamiento. En el grupo B, tratado con CTM, se obtuvo resultado excelente en 24 casos (80%), bueno en dos casos, satisfactorio en 1 caso, y malo en 3 pacientes. Se produjo resistencia secundaria al tratamiento, en el 13% de los casos del grupo B, tratado con CTM, resultado que es de significancia estadística (P < 0.05)