ABSTRACT
BACKGROUND: Pyruvate kinase deficiency (PKD) is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. The disease shows a marked variability in clinical expression. We studied the molecular features of nine unrelated Argentinian patients with congenital hemolytic anemia associated with erythrocyte pyruvate kinase deficiency. DESIGN AND METHODS: Routine hematologic investigations were performed to rule out other causes of chronic hemolytic anemia. Sanger sequencing and in-sílico analysis were carried out to identify and characterize the genetics variants. RESULTS: Six different novel missense variants were detected among the 18 studied alleles: c.661 G > C (Asp221His), c.956 G > T (Gly319Val), c.1595 G > C (Arg532Pro), c.347 G > A (Arg116Gln), c.1232 G > T (Gly411Val), c.1021G > A (Gly341Ser). Structural implications of amino-acid substitutions were correlated with the clinical phenotypes seen in the probands. CONCLUSIONS: This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency in Argentina and the second from South America that would contribute to our knowledge on the distribution and frequency of PKLR variants in our population but also offer new insights into the interpretation of the effect of PKLR variants and phenotype.
Subject(s)
Alleles , Anemia, Hemolytic, Congenital Nonspherocytic/genetics , Mutation, Missense , Pyruvate Kinase/deficiency , Pyruvate Metabolism, Inborn Errors/genetics , Adolescent , Adult , Amino Acid Substitution , Argentina , Child , Child, Preschool , Female , Humans , Infant , Male , Pyruvate Kinase/geneticsSubject(s)
Anemia, Hemolytic/pathology , Erythrocytes/pathology , Glucosephosphate Dehydrogenase Deficiency/pathology , Glucosephosphate Dehydrogenase/genetics , Protein Isoforms/genetics , Anemia, Hemolytic/genetics , Chronic Disease , Erythrocytes/metabolism , Glucosephosphate Dehydrogenase Deficiency/genetics , Humans , Infant , MaleABSTRACT
La deficiencia de vitamina B12 es una de las complicaciones más graves del vegetarianismo. Los lactantes hijos de madres veganas tienen mayor riesgo de deficiencia grave y son más lábiles ante sus efectos. La deficiencia de B12 no es, por lo general, sospechada por el pediatra en lactantes previamente sanos con síntomas neurológicos, ya que las manifestaciones iniciales son inespecíficas: apatía, rechazo del alimento y pérdida de pautas madurativas. La anamnesis nutricional es fundamental para detectar riesgo de déficit de esta vitamina en lactantes. El objetivo de este trabajo es describir a un grupo de lactantes, hijos de madres veganas, con déficit de B12 y compromiso neurológico grave: apneas centrales, convulsiones, hipotonía, pérdida de conexión con el medio y de pautas madurativas. Nuestro propósito es alertar sobre la importancia de suplir B12 a las madres veganas desde antes de la concepción hasta el fin de la lactancia.
Vitamin B12 deficiency is one of the most serious complications of vegetarianism and its variants. Infants born to vegan mothers are at greater risk of serious deficiency, being more vulnerable to their effects. B12 deficiency is not usually suspected by the pediatrician in healthy infants with neurological symptoms. The manifestations are nonspecific: apathy, rejection of food and loss of maturational patterns. A nutritional history of the mother, mainly if she is vegetarian, to estimate her reserves is fundamental to detect risk of deficiency of this vitamin in the small child. The objective of this work is to describe a group of infants, children of vegan mothers, with B12 deficiency and serious neurological compromise: central apneas, seizures, hypotonia, loss of connection with the environment and maturational patterns. Our purpose is to alert about the importance of supplying vegan mothers with B12 before conception until the end of breastfeeding.
Subject(s)
Humans , Infant , Pediatrics , Diet, Vegetarian , Vitamin B 12 Deficiency , Infant , Nervous System DiseasesABSTRACT
Vitamin B12 deficiency is one of the most serious complications of vegetarianism and its variants. Infants born to vegan mothers are at greater risk of serious deficiency, being more vulnerable to their effects. B12 deficiency is not usually suspected by the pediatrician in healthy infants with neurological symptoms. The manifestations are nonspecific: apathy, rejection of food and loss of maturational patterns. A nutritional history of the mother, mainly if she is vegetarian, to estimate her reserves is fundamental to detect risk of deficiency of this vitamin in the small child. The objective of this work is to describe a group of infants, children of vegan mothers, with B12 deficiency and serious neurological compromise: central apneas, seizures, hypotonia, loss of connection with the environment and maturational patterns. Our purpose is to alert about the importance of supplying vegan mothers with B12 before conception until the end of breastfeeding.
La deficiencia de vitamina B12 es una de las complicaciones más graves del vegetarianismo. Los lactantes hijos de madres veganas tienen mayor riesgo de deficiencia grave y son más lábiles ante sus efectos. La deficiencia de B12 no es, por lo general, sospechada por el pediatra en lactantes previamente sanos con síntomas neurológicos, ya que las manifestaciones iniciales son inespecíficas: apatía, rechazo del alimento y pérdida de pautas madurativas. La anamnesis nutricional es fundamental para detectar riesgo de déficit de esta vitamina en lactantes. El objetivo de este trabajo es describir a un grupo de lactantes, hijos de madres veganas, con déficit de B12 y compromiso neurológico grave: apneas centrales, convulsiones, hipotonía, pérdida de conexión con el medio y de pautas madurativas. Nuestro propósito es alertar sobre la importancia de suplir B12 a las madres veganas desde antes de la concepción hasta el fin de la lactancia.
