Importance of genetic sequencing studies in managing chronic neonatal diarrhea: a case report of a novel variant in the glucose–galactose transporter SLC5A1

IntroductionCongenital glucose–galactose malabsorption (CGGM) is a rare autosomal recessive disorder that primarily causes chronic intractable diarrhea. This study aims to describe the clinical history, laboratory profile, diagnostic workflow, and management of the first patient reported with CGGM in Mexico.MethodsThe case involves a Mexican female infant with recurrent admissions to the emergency room since birth due to chronic diarrhea.ResultsThe infant was born at term by C-section with a birth weight of 3.120 kg and height of 48 cm for consanguineous parents. She had been breastfed until day 5 of her life when she presented lethargy, diarrhea, abdominal discomfort, and jaundice. During the first evaluation at the emergency room, the significant laboratory finding was blood tyrosine elevation; afterward, amino acid and succinylacetone determinations were obtained, discarding tyrosinemia. When admitted to the hospital, an abdominal ultrasound detected a duplex collecting system. At this time, rice formula was introduced to the patient. She was discharged with jaundice improvement, but diarrhea persisted. Several formula changes had been made from rice to extensively hydrolyzed casein protein to whey-based, with no clinical improvement; the patient still had 10–12 excretions daily. In the second hospitalization, the patient presented anemia, severe dehydration, hyperammonemia, and renal tubular acidosis. A next-generation sequencing panel for inborn errors of metabolism and congenital diarrhea was performed, identifying a homozygous variant in SLC5A1 (c.1667T > C). The diagnosis of CGGM was made at 3 months of age. The infant was initially treated with a modular galactose–glucose-free formula with oil, fructose, casein, minerals, and vitamins until a commercial fructose-based formula was introduced. This led to a complete resolution of diarrhea and improved nutritional status.DiscussionDiagnosing CGGM is challenging for clinicians, and next-generation sequencing is a valuable tool for providing appropriate treatment. More detailed information on patients with this condition might lead to possible phenotype–genotype correlations. This case's primary clinical and biochemical findings were chronic diarrhea, anemia, jaundice, renal tubular acidosis, hyperammonemia, and initial hypertyrosinemia. Symptoms were resolved entirely with the fructose-based formula

Current practices and challenges in the diagnosis and management of pku in Latin America: A multicenter survey

This study aimed to describe the current practices in the diagnosis and dietary management of phenylketonuria (PKU) in Latin America, as well as the main barriers to treatment. We developed a 44-item online survey aimed at health professionals. After a pilot test, the final version was sent to 25 practitioners working with inborn errors of metabolism (IEM) in 14 countries. Our results include 22 centers in 13 countries. Most countries (12/13) screened newborns for PKU. Phenylalanine (Phe) targets at different ages were very heterogeneous among centers, with greater consistency at the 0–1 year age group (14/22 sought 120–240 µmol/L) and the lowest at >12 years (10 targets reported). Most countries had only unflavored powdered amino acid substitutes (10/13) and did not have low-protein foods (8/13). Only 3/13 countries had regional databases of the Phe content of foods, and only 4/22 centers had nutrient analysis software. The perceived obstacles to treatment were: low purchasing power (62%), limited/insufficient availability of low-protein foods (60%), poor adherence, and lack of technical resources to manage the diet (50% each). We observed a heterogeneous scenario in the dietary management of PKU, and most countries experienced a lack of dietary resources for both patients and health professionals.Fil: Poloni, Soraia. Hospital de Clínicas de Porto Alegre; BrasilFil: Dos Santos, Bruna Bento. Universidade Federal do Rio Grande do Sul; Brasil. Hospital de Clínicas de Porto Alegre; BrasilFil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Specola, Norma. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Pereyra, Marcela. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Saborío Rocafort, Manuel. Universidad de Costa Rica; Costa RicaFil: Salazar, María Florencia. Universidad de Chile; ChileFil: Leal-Witt, María Jesús. Universidad de Chile; ChileFil: Castro, Gabriela. Universidad de Chile; ChileFil: Peñaloza, Felipe. Universidad de Chile; ChileFil: Wong, Sunling Palma. Hospital Nacional de Niños; Costa RicaFil: Badilla Porras, Ramsés. Hospital Nacional de Niños; Costa RicaFil: Ortiz Paranza, Lourdes. Ministerio de Salud Pública y Bienestar Social; ParaguayFil: Sanabria, Marta Cristina. Hospital de Clínicas; ParaguayFil: Vela Amieva, Marcela. Instituto Nacional de Pediatría; MéxicoFil: Morales, Marco. No especifíca;Fil: Caro Naranjo, Amanda Rocío. Pontificia Universidad Javeriana; ColombiaFil: Mahfoud, Antonieta. Pontificia Universidad Javeriana; ColombiaFil: Colmenares, Ana Rosa. Hospital Clinica Caracas-Materno Infantil de Caricuao; VenezuelaFil: Lemes, Aida. Instituto de Seguridad Social; UruguayFil: Sotillo Lindo, José Fernando. Hospital de especialidades Pediátricas “Omar Torrijos Herrera"; PanamáFil: Perez, Ceila. Robert Reid Cabral Children’s Hospital; República DominicanaFil: Martínez Rey, Laritza. Centro Nacional de Genética Médica; CubaFil: Zayas Torriente, Georgina María. Centro de Nutrición e Higiene de los Alimentos del Instituto Nacional de Higiene, Epidemiología y Microbiología; CubaFil: Farret Refosco, Lilia. Hospital de Clínicas de Porto Alegre; BrasilFil: Doederlein Schwartz, Ida Vanessa. Universidade Federal do Rio Grande do Sul; Brasil. Hospital de Clínicas de Porto Alegre; BrasilFil: Cornejo, Veronica. Universidad de Chile; Chil

Neonatal screening to detect critical congenital cardiac disease. A revolution in pediatrics

There is solid evidence that demonstrate the usefulness of routine oxygen saturation testing in every apparently healthy newborn after 24 hours of life and before 48 hours. This procedure is known as “newborn screening for critical congenital heart disease” and serves to detect timely those congenital structural cardiac malformations with hypoxema, such as heart syndrome, pulmonary valve atresia, truncus arteriosus, total anomalous pulmonary vein connection, complete transposition of the great arteries, tetralogy of Fallot and tricuspid valve atresia. This test has been included in the mandatory neonatal screening panel of many countries and its generalization all over the world, seems imminent

Theorical and practical bases for blood sample collection from the heel of newborns for neonatal screening

Newborn screening (NBS) is a preventive study whose benefit has been established by solid scientific evidence. In most developed countries screening is done with 5 or 6 blood spots obtained by the puncture of the plantar surface of the infant’s heel with a sterile lancet, and collected in a special filter paper (Guthrie’s card). Despite its apparent simplicity, NBS laboratories commonly receive a large number of samples collected incorrectly and technically unsuitable for perfor4ming biochemical determinations. The aim of the present paper is to offer recommendations based on scientific evidence, for the properly blood collection on filter paper for NBS programs

Polyunsaturated long-chain fatty acids in hyperphenylalaninemias

Patients with hyperphenylalaninemia (HFA) must follow a restricted protein diet, which deprives them of natural dietary sources of polyunsaturated fatty acids (LC-PUFA) that lead to neurological deficits, not related to high phenylalanine blood levels. There is strong evidence of the benefits of docosahexaenoic acid (DHA) supplement, a long chain polyunsaturated fatty acid (LC-PUFA) that has several essential roles in the brain and in the retina. More studies are required to determine the DHA dosage and its sources at different stages of life in this HFA patients

Ophthalmologic findings in patients with inborn errors of metabolism

In patient with inborn errors of metabolism (IEM), the presence of characteristic findings in ophthalmic assessment are important for the diagnosis. The presence of cataracts, cherry-red spot, corneal opacities, corneal crystals, lens dislocation, gyrate atrophy, etc., are some of the ocular abnormalities present in certain IEM. The role of the ophthalmologist in the evaluation of patients with IEM is essential. We describe the most frequent ocular findings in patients with different IEM, which are a diagnostic aid for ophthalmologists and pediatricians

Actualización sobre la lactancia materna en los recién nacidos con errores innatos del metabolismo intermediario

Los errores innatos del metabolismo intermediario (EIMi) son un grupo de enfermedades monogénicas que afectan alguna vía del metabolismo de las proteínas, los hidratos de carbono o los lípidos; cuando no son tratados a tiempo, se asocian con una elevada morbimortalidad. A la fecha, la piedra angular del tratamiento de los EIMi ha sido la terapia nutricional, cuyo propósito es evitar la acumulación de metabolitos tóxicos al restringir los sustratos que están involucrados en la vía afectada. El manejo nutricional en lactantes incluye una fórmula metabólica sin los nutrimentos involucrados en el EIMi más el aporte de alimentación al seno materno o fórmula infantil. Por el perfil de aminoácidos, la proporción de ácidos grasos esenciales y la protección contra enfermedades, la leche materna resulta un alimento ideal para los pacientes con EIMi. El objetivo de esta revisión de la literatura sobre la lactancia materna en algunos EIMi es servir de guía para el personal de salud involucrado en la atención médica de estos pacientes. La lactancia materna puede ser llevada a cabo de forma exitosa en pacientes con EIMi siempre que exista un seguimiento estrecho y continuo, de preferencia en centros especializados. El profesional de la nutrición y el pediatra deben individualizar las recomendaciones para proporcionar una lactancia a libre demanda en conjunto con una fórmula metabólica o una lactancia materna cuantificada, y con ello lograr una adecuada evolución en estos pacientes

Conventional Phenylketonuria Treatment

Phenylketonuria (PKU) is caused by a deficient activity of enzyme phenylalanine (Phe) hydroxylase, which results in high Phe blood concentration, which is toxic to the central nervous system. The fundamental purpose of nutritional treatment is to reduce and maintain blood Phe between 2 mg/dL (120 µmol/L) and 6 mg/dL (360 µmol/L) in order to prevent neuropathogenic complications. At the same time, nutrition support must provide enough energy and nutrients to promote normal growth and development and also to avoid vitamin and mineral deficiencies. Phenylketonuria treatment must be maintained long-life and its adherence must be frequently assessed. The amount of Phe required by patients with PKU varies throughout life and must be adjusted according to individual tolerance, residual phenylalanine hydroxylase enzymatic activity, age, sex, growth rate, protein intake, and nutritional and biochemical status among others. Treatment must be done by trained personnel. It is necessary to unify treatment criteria and further research must be done