ABSTRACT
Serine biosynthesis defects are autosomal recessive metabolic disorders resulting from the deficiency of any of the three enzymes involved in de novo serine biosynthesis, specifically phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). In this study, we performed metabolomic profiling on 4 children with serine biosynthesis defects; 3 with PGDH deficiency and 1 with PSAT deficiency. The evaluations were performed at baseline and with serine and glycine supplementation. Metabolomic profiling performed at baseline showed low phospholipid species, including glycerophosphocholine, glycerophosphoethanolamine, and sphingomyelin. All children had low serine and glycine as expected. Low glycerophosphocholine compounds were found in 4 children, low glycerophosphoethanolamine compounds in 3 children, and low sphingomyelin species in 2 children. Metabolic profiling with serine and glycine supplementation showed normalization of most of the low phospholipid compounds in the 4 children. Phospholipids are the major component of plasma and intracellular membranes, and phosphatidylcholine is the most abundant phospholipid of all mammalian cell types and subcellular organelles. Phosphatidylcholine is of particular importance for the nervous system, where it is essential for neuronal differentiation. The observed low phosphatidylcholine species in children with serine biosynthesis defects that improved after serine supplementation, supports the role of serine as a significant precursor for phosphatidylcholine. The vital role that phosphatidylcholine has during neuronal differentiation and the pronounced neurological manifestations in serine biosynthesis defects suggest that phosphatidylcholine deficiency occurring secondary to serine deficiency may have a significant contribution to the development of the neurological manifestations in individuals with serine biosynthesis defects.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/metabolism , Dietary Supplements , Glycine/administration & dosage , Microcephaly/metabolism , Phosphatidylcholines/metabolism , Phosphoglycerate Dehydrogenase/deficiency , Psychomotor Disorders/metabolism , Seizures/metabolism , Serine/biosynthesis , Transaminases/deficiency , Carbohydrate Metabolism, Inborn Errors/blood , Carbohydrate Metabolism, Inborn Errors/diet therapy , Cell Differentiation , Child , Child, Preschool , Female , Glycine/blood , Humans , Infant , Male , Metabolomics/methods , Microcephaly/blood , Microcephaly/diet therapy , Neurons/metabolism , Phosphoglycerate Dehydrogenase/blood , Phosphoglycerate Dehydrogenase/metabolism , Psychomotor Disorders/blood , Psychomotor Disorders/diet therapy , Seizures/blood , Seizures/diet therapy , Serine/administration & dosage , Serine/blood , Transaminases/blood , Transaminases/metabolismABSTRACT
Abstract This summary aimed to synthesize the protocol guidelines of Pernambuco, the Ministry of Health and the Centers for Disease Control and Prevention which deal with health care related to Zika virus infection during pregnancy and the preliminary procedures for surveillance on microcephaly cases including nutritional care. With the increase of number of cases on this event since August, 2015, it was necessary to reorganize the prenatal care which is offered to pregnant women, including the protocols in order to reduce the chances of a possible contamination of the virus, to detect previously suspected cases as well as perform follow up on confirmed cases. The gaps in the knowledge of this morbidity, it should be noted that the information and recommendations are subject to revision due to possible incorporation of new knowledge and other evidence, as well as the need for adequacy of surveillance actions in new epidemiological scenarios. It is known that cases of nutritional deficiencies are capable of producing malformation of the Central Nervous System, including microcephaly. In the analysis of the protocols, there were no changes as to the nutritional recommendations already established for the low-risk pregnant women. The authors presented a hypothesis and conceptually, as a prevention measurement, the inclusion of prenatal care to prevent and control isolated or multiple deficiencies associated to microcephaly, such as protein, vitamin A, iodine, folate, B12, vitamin D, biotin, zinc and selenium.
Resumo Objetivou-se sintetizar as orientações dos protocolos de Pernambuco, Ministério da Saúde e do Centers for Disease Control and Prevention que tratam sobre atenção à saúde relacionada à infecção pelo Vírus Zika na gestação e procedimentos preliminares para vigilância dos casos de microcefalia, incluindo os cuidados nutricionais. Com o aumento no número de casos deste evento a partir de agosto/2015, foi necessária reorganização na atenção pré-natal ofertada às gestantes, incluindo protocolos para diminuir chances de possível contaminação com o vírus, detectar precocemente casos suspeitos e seguimento dos casos confirmados. Tendo em vista as lacunas no conhecimento acerca desta morbidade, ressalta-se que as informações e recomendações são passíveis de revisão frente às eventuais incorporações de novos conhecimentos e outras evidências, bem como necessidade de adequações das ações de vigilância em cenários epidemiológicos novos. É conhecido que muitas situações de deficiências nutricionais são capazes de produzir má formação do Sistema Nervoso Central, incluindo a microcefalia. Na análise dos protocolos, não foram observadas mudanças quanto às recomendações nutricionais já estabelecidas para as gestantes de baixo risco. Sendo assim, os autores apresentam como hipótese e, conceitualmente, como medida propositiva, inclusão de cuidados pré-natais e periconcepcionais para prevenção e controle de carências isolados ou múltiplos associados com a microcefalia, tais como deficiência proteica, de vitamina A, iodo, folato, B12, vitamina D, biotina, zinco e selênio.
Subject(s)
Humans , Female , Pregnancy , Clinical Protocols , Microcephaly/diet therapy , Prenatal Care , Zika Virus Infection/diet therapy , Deficiency Diseases , Delivery of Health Care , PregnancyABSTRACT
Glucose transport protein deficiency due to mutation in the GLUT1 gene is characterized by infantile onset and chronic seizure disorder, microcephaly, global developmental delays, and hypoglycorrhachia. We describe a 10-year-old normocephalic male with prominent ataxia, dystonia, choreoathetosis, and GLUT1 deficiency whose motor abnormalities improved with a ketogenic diet. We illustrate the motor abnormalities, at baseline and after ketogenic diet, that characterize this unusual case. This case broadens the phenotype of GLUT1 deficiency and illustrates the importance of cerebrospinal fluid (CSF) evaluation in detecting potentially treatable conditions in children with undiagnosed movement disorders.
