RESUMO
Autosomal recessive glutaric acidaemia type I (GA-I) is a rare hereditary metabolic disease characterized by increased organic acids and neurologic symptoms. Although numerous variants in the GCDH gene have been identified to be connected with the pathogenesis of GA-I, the relationship between genotype and phenotype remains uncertain. In this study, we evaluated genetic data for two GA-I patients from Hubei, China, and we reviewed the previous research findings to clarify the genetic heterogeneity of GA-I and identify the potential causative variants. After we extracted genomic DNA from peripheral blood samples obtained from two unrelated Chinese families, we used target capture high-throughput sequencing combined with Sanger sequencing to determine likely pathogenic variants in the two probands. Electronic databases were also searched for the literature review. The genetic analysis revealed two compound heterozygous variants in the GCDH gene expected to lead to GA-I in the two probands (P1 and P2), with P1 carrying two known variants (c.892G > A/p. A298T and c.1244-2A > C/IVS10-2A > C) and P2 harbouring two novel variants (c.370G > T/p.G124W and c.473A > G/p.E158G). In the literature review, the most common alleles in low excretors (i.e., individuals with low excretion of GA) were R227P, V400M, M405V, and A298T, with variation in the severity of clinical phenotypes. Overall, we identified two novel GCDH gene candidate pathogenic variants in a Chinese patient, enriching the GCDH gene mutational spectrum and providing a solid foundation for the early diagnosis of GA-I patients with low excretion.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , População do Leste Asiático , Humanos , Erros Inatos do Metabolismo dos Aminoácidos/genética , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Glutaril-CoA Desidrogenase/genética , Mutação , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: As modern medicine is advancing, younger, small, and more complex children are becoming multi-organ transplant candidates. This brings up new challenges in all aspects of their care. METHODS: We describe the first report of a small child receiving a simultaneous liver and kidney transplant and abdominal rectus sheath fascia transplant on the background of Williams syndrome and methylmalonic acidaemia. At the time of transplantation, the child was 3 years old, weighed 14.0 kg, had chronic kidney disease stage V, and had not yet started any other form of kidney replacement therapy. RESULTS: There were many anaesthetic, medical, metabolic, and surgical challenges to consider in this case. A long general anaesthetic time increased the risk of cardiac complications and metabolic decompensation. Additionally, the small size of the patient and the organ size mis-match meant that primary abdominal closure was not possible. The patient's recovery was further complicated by sepsis, transient CNI toxicity, and de novo DSAs. CONCLUSIONS: Through a multidisciplinary approach between 9 specialties in 4 hospitals across England and Wales, and detailed pre-operative planning, a good outcome was achieved for this child. An hour by hour management protocol was drafted to facilitate transplant and included five domains: 1. management at the time of organ offer; 2. before the admission; 3. at admission and before theatre time; 4. intra-operative management; and 5. post-operative management in the first 24 h. Importantly, gaining a clear and in depth understanding of the metabolic state of the patient pre- and peri-operatively was crucial in avoiding metabolic decompensation. Furthermore, an abdominal rectus sheath fascia transplant was required to achieve abdominal closure, which to our knowledge, had never been done before for this indication. Using our experience of this complex case, as well as our experience in transplanting other children with MMA, and through a literature review, we propose a new perioperative management pathway for this complex cohort of transplant recipients.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Falência Renal Crônica , Transplante de Rim , Transplante de Fígado , Criança , Humanos , Pré-Escolar , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Falência Renal Crônica/complicações , Fígado , Transplante de Rim/efeitos adversos , Transplante de Rim/métodosRESUMO
OBJECTIVES: To assess labour characteristics in relation to the occurrence of Composite Adverse neonatal Outcome (CAO) within a cohort of fetuses with metabolic acidaemia. DESIGN: Retrospective cohort study. SETTING: Three Italian tertiary maternity units. POPULATION: 431 neonates born with acidaemia ≥36 weeks. METHODS: Intrapartum CTG traces were assigned to one of these four types of labour hypoxia: acute, subacute, gradually evolving and chronic hypoxia. The presence of CAO was defined by the occurrence of at least one of the following: Sarnat Score grade ≥2, seizures, hypothermia and death <7 days from birth. MAIN OUTCOME MEASURES: To compare the type of hypoxia on the intrapartum CTG traces among the acidaemic neonates with and without CAO. RESULTS: The occurrence of a CAO was recorded in 15.1% of neonates. At logistic regression analysis, the duration of the hypoxia was the only parameter associated with CAO in the case of an acute or subacute pattern (odds ratio [OR] 1.3; 95% CI 1.02-1.6 and OR 1.04; 95% CI 1.0-1.1, respectively), whereas both the duration of the hypoxic insult and the time from PROM to delivery were associated with CAO in those with a gradually evolving pattern (OR 1.13; 95% CI 1.01-1.3 and OR 1.04; 95% CI 1.0-1.7, respectively). The incidence of CAO was higher in fetuses with chronic antepartum hypoxia than in those showing CTG features of intrapartum hypoxia (64.7 vs. 13.0%; P < 0.001). CONCLUSIONS: The frequency of CAO seems related to the duration and the type of the hypoxic injury, being higher in fetuses showing CTG features of antepartum chronic hypoxia. TWEETABLE ABSTRACT: This study demonstrates that in a large population of neonates with metabolic acidaemia at birth, the overall incidence of short-term adverse outcome is around 15%. Such risk seems closely correlated to the duration and the type of hypoxic injury, being higher in fetuses admitted in labour with antepartum chronic hypoxia than those experiencing intrapartum hypoxia.
Assuntos
Acidose , Acidose/diagnóstico , Acidose/epidemiologia , Estudos de Coortes , Feminino , Humanos , Hipóxia/epidemiologia , Hipóxia/etiologia , Recém-Nascido , Morbidade , Gravidez , Estudos RetrospectivosRESUMO
Increased fetal heart rate variability (FHRV) in intrapartum cardiotocographic recording has been variably defined and poorly understood, limiting its clinical utility. Both preclinical (animal) and clinical (human) evidence support that increased FHRV is observed in the early stage of intrapartum fetal hypoxaemia but can also be observed in a subset of fetuses during the preterminal stage of repeated hypoxaemia. This review of available evidence provides data and expert opinion on the pathophysiology of increased FHRV, its clinical significance and a stepwise approach regarding the management of this pattern, and propose recommendations for standardisation of related terminology.
Assuntos
Frequência Cardíaca Fetal , Trabalho de Parto , Animais , Cardiotocografia , Feminino , Frequência Cardíaca Fetal/fisiologia , Humanos , Hipóxia , Parto , GravidezRESUMO
Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article, we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re-evaluated, analysed and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well-informed decisions in the context of MMA and PA patient care.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/terapia , Acidemia Propiônica/diagnóstico , Acidemia Propiônica/terapia , Gerenciamento Clínico , HumanosRESUMO
Many neurodegenerative and inherited metabolic diseases frequently compromise nervous system function, and mitochondrial dysfunction and oxidative stress have been implicated as key events leading to neurodegeneration. Mitochondria are essential for neuronal function; however, these organelles are major sources of endogenous reactive oxygen species and are vulnerable targets for oxidative stress-induced damage. The brain is very susceptible to oxidative damage due to its high metabolic demand and low antioxidant defence systems, therefore minimal imbalances in the redox state can result in an oxidative environment that favours tissue damage and activates neuroinflammatory processes. Mitochondrial-associated molecular pathways are often compromised in the pathophysiology of neurodegeneration, including the parkin/PINK1, Nrf2, PGC1α, and PPARγ pathways. Impairments to these signalling pathways consequently effect the removal of dysfunctional mitochondria, which has been suggested as contributing to the development of neurodegeneration. Mitochondrial dysfunction prevention has become an attractive therapeutic target, and there are several molecular pathways that can be pharmacologically targeted to remove damaged mitochondria by inducing mitochondrial biogenesis or mitophagy, as well as increasing the antioxidant capacity of the brain, in order to alleviate mitochondrial dysfunction and prevent the development and progression of neurodegeneration in these disorders. Compounds such as natural polyphenolic compounds, bioactive quinones, and Nrf2 activators have been reported in the literature as novel therapeutic candidates capable of targeting defective mitochondrial pathways in order to improve mitochondrial function and reduce the severity of neurodegeneration in these disorders.
Assuntos
Doenças Metabólicas/metabolismo , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/metabolismo , Animais , Antioxidantes/farmacologia , Humanos , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/fisiopatologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Mitocôndrias/fisiologia , Mitofagia/efeitos dos fármacos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/fisiopatologia , Neurônios/metabolismo , Oxirredução , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Glutaric acidaemia type I (GA-I) is a cerebral organic disorder characterized by the accumulation of glutaric acid (GA) and seizures. As seizures are precipitated in children with GA-I and the mechanisms underlying this disorder are not well established, we decided to investigate the role of nitric oxide (NO) in GA-induced convulsive behaviour in pup rats. Pup male Wistar rats (18-day-old) were anesthetized and placed in stereotaxic apparatus for cannula insertion into the striatum for injection of GA. The experiments were performed 3 days after surgery (pup rats 21-day-old). An inhibitor of NO synthesis (N-G-nitro-l-arginine methyl ester-L-NAME, 40 mg/kg) or saline (vehicle) was administered intraperitoneally 30 min before the intrastriatal injection of GA (1 µl, 1.3 µmol/striatum) or saline. Immediately after the intrastriatal injections, the latency and duration of seizures were recorded for 20 min. The administration of L-NAME significantly increased the latency to the first seizure episode and reduced the duration of seizures induced by GA in pup rats. The administration of the NO precursor l-arginine (L-ARG; 80 mg/kg) prevented the effects of L-NAME. Besides, GA significantly increased nitrate and nitrite (NOx) levels in the striatum of pup rats and the preadministration of L-NAME prevented this alteration. L-ARG blocked the reduction of striatal NOx provoked by L-NAME. These results are experimental evidence that NO plays a role in the seizures induced by GA in pup rats, being valuable in understanding the physiopathology of neurological signs observed in children with this organic acidaemia and to develop new therapeutic strategies.
Assuntos
Óxido Nítrico , Convulsões , Animais , Arginina , Inibidores Enzimáticos/farmacologia , Glutaratos , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Ratos Wistar , Convulsões/induzido quimicamenteRESUMO
BACKGROUND: Resuscitation guidelines list acidaemia as a potentially reversible cause of cardiac arrest without specifying the threshold defining acidaemia. We examined the association between early intra-arrest arterial blood gas (ABG) data and outcomes of in-hospital cardiac arrest (IHCA). METHODS: This single-centred retrospective study reviewed patients with IHCA between 2006 and 2015. Early intra-arrest ABG data were measured within 10 min of initiating cardiopulmonary resuscitation. The ABG analysis included measurements of blood pH, PaCO2, and HCO3-. RESULTS: Among the 1065 included patients, 60 (5.6%) achieved neurologically intact survival. Mean blood pH was 7.2. Mean PaCO2 and HCO3- levels were 59.7 mmHg and 22.1 mmol/L, respectively. A blood pH of 7.2 was identified by a generalised additive models plot to define severe acidaemia. The PaCO2 level was higher in patients with severe acidaemia (mean: 74.5 vs. 44.1 mmHg) than in those without. Multivariable logistic regression analyses indicated that blood pH > 7.2 was associated with a favourable neurological recovery (odds ratio [OR]: 2.79, 95% confidence interval [CI]: 1.43-5.46; p-value = 0.003) and blood pH was positively associated with survival at hospital discharge (OR: 5.80, 95% CI: 1.62-20.69; p-value = 0.007). CONCLUSION: Early intra-arrest blood pH was associated with IHCA outcomes, while levels of PaCO2 and HCO3- were not. A blood pH of 7.2 could be used as the threshold defining severe acidaemia during arrest and help profile patients with IHCA. Innovative interventions should be developed to improve the outcomes of patients with severe acidaemia, such as novel ventilation methods.
Assuntos
Acidose/sangue , Gasometria , Reanimação Cardiopulmonar , Parada Cardíaca/sangue , Alta do Paciente/estatística & dados numéricos , Acidose/mortalidade , Acidose/fisiopatologia , Adulto , Idoso , Bicarbonatos/sangue , Dióxido de Carbono/sangue , Feminino , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Mortalidade Hospitalar , Humanos , Concentração de Íons de Hidrogênio , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan/epidemiologiaRESUMO
Non-invasive ventilation (NIV) treatment decisions are poorly understood for patients with COPD exacerbation complicated by acute hypercapnic respiratory failure and respiratory acidaemia (ECOPD-RA). We identified 420 NIV-eligible patients from the DECAF study cohorts admitted with an ECOPD-RA. Using bivariate and multivariate analyses, we examined which indices were associated with clinicians' decisions to start NIV, including whether the presence of pneumonia was a deterrent. Admitting hospital, admission from institutional care, partial pressure of oxygen, cerebrovascular disease, pH, systolic blood pressure and white cell count were all associated with the provision of NIV. Of these indices, only pH was also a predictor of inpatient death. Those not treated with NIV included those with milder acidaemia and higher (and sometimes excessive) oxygen levels, and a frailer population with higher Extended Medical Research Council Dyspnoea scores, presumably deemed not suitable for NIV. Pneumonia was not associated with NIV treatment; 34 of 111 (30.6%) NIV-untreated patients had pneumonia, whilst 107 of 309 (34.6%) NIV-treated patients had pneumonia (p = 0.483). In our study, one in four NIV-eligible patients were not treated with NIV. Clinicians' NIV treatment decisions are not based on those indices most strongly associated with mortality risk. One of the strongest predictors of whether a patient received a life-saving treatment is which hospital they attended. Further research is required to aid in the risk stratification of this patient group which may help standardise and improve care.
Assuntos
Acidose Respiratória/terapia , Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia , Insuficiência Respiratória/complicações , Insuficiência Respiratória/terapia , Acidose Respiratória/complicações , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Hipercapnia/complicações , Hipercapnia/terapia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Pneumonia/complicações , Pneumonia/terapia , Padrões de Prática Médica , Fatores de Risco , Reino UnidoRESUMO
AIM: Newborns with inborn errors of metabolism can present with hyperammonaemic coma. In this study, we evaluated the effect of peritoneal dialysis on plasma ammonium levels and on the short-term outcome in neonatal patients with urea cycle defects and organic acidaemia. METHODS: Data from infants with hyperammonaemia due to urea cycle defects or organic acidaemia treated with dialysis were collected and retrospectively analyzed. The results of patient groups (group I, survived; and group II, died) were compared. RESULTS: Fourteen neonates were enrolled in this study. In group I, plasma ammonium levels before dialysis were median (IQR) 1652 µg/dL (1165-2098 µg/dL); in group II, they were 1289 µg/dL (1070-5550 µg/dL). There was no statistically significant difference. Urea cycle defects were diagnosed in eight, and organic acidaemia in six patients. The duration of a blood ammonia level >200 µg/dL was longer in group II (P = 0.04). A <60.8% decline in the ammonia level from the beginning of dialysis to the 12th hour of dialysis carried a 3.33-fold higher risk of mortality, when compared with a greater decline. Five patients with urea cycle defects, and one with organic acidaemia, died. The mortality risk was 8.33-fold (95% CI = 0.63-90.86) higher for patients with urea cycle defects than for those with organic acidaemia. CONCLUSION: In patients with hyperammonaemia treated with peritoneal dialysis, the rate of ammonia removal and the underlying aetiology appear to be important prognostic factors. Neonates with organic acidaemia who are admitted to centres without continuous renal replacement therapy facilities can be effectively treated with peritoneal dialysis.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Amônia/sangue , Hiperamonemia , Distúrbios Congênitos do Ciclo da Ureia , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/mortalidade , Feminino , Humanos , Hiperamonemia/sangue , Hiperamonemia/diagnóstico , Hiperamonemia/etiologia , Hiperamonemia/terapia , Recém-Nascido , Masculino , Mortalidade , Diálise Peritoneal , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Turquia/epidemiologia , Distúrbios Congênitos do Ciclo da Ureia/sangue , Distúrbios Congênitos do Ciclo da Ureia/diagnóstico , Distúrbios Congênitos do Ciclo da Ureia/mortalidadeAssuntos
Anestesia Obstétrica , Raquianestesia , Hipotensão , Gravidez , Feminino , Humanos , Norepinefrina/uso terapêutico , Raquianestesia/efeitos adversos , Estudos Retrospectivos , Vasoconstritores/uso terapêutico , Fenilefrina , Cesárea , Débito Cardíaco , Hipotensão/tratamento farmacológico , Método Duplo-CegoRESUMO
BACKGROUND: To examine the impact of occiput posterior position, compared to occiput anterior position, on neonatal outcomes in a setting where delayed pushing is practiced. The specific aim was to estimate the risk of acidaemia. METHODS: Cohort study from a university hospital in Sweden between 2004 and 2012. Information was collected from a local database of 35,546 births. Umbilical artery sampling was routine. Outcomes were: umbilical artery pH < 7.00 and <7.10 and short-term neonatal morbidity. The association between occiput posterior position and neonatal outcomes was examined using logistic regression analysis, presented as adjusted odds ratio (AOR) with 95% confidence interval (CI). RESULTS: Of 27,648 attempted vaginal births, 1292 (4.7%) had occiput posterior position. Compared with occiput anterior, there was no difference in pH < 7.00 (0.4% vs. 0.5%) but a higher rate of pH < 7.10 in occiput posterior births (3.8 vs. 5.5%). Logistic regression analysis showed no increased risk of pH < 7.10 (AOR 1.28 95% CI 0.93-1.74) when occiput posterior was compared with occiput anterior births but, an increased risk of Apgar score < 7 at 5 min (AOR 1.84, 95% CI 1.11-3.05); neonatal care admission (AOR 1.68, 95% CI 1.17-2.42) and composite morbidity (AOR 1.66, 95% CI 1.19-2.31). CONCLUSIONS: With delayed pushing, birth in occiput posterior compared with anterior position is not associated with acidaemia. The higher risk of neonatal morbidity is of concern and any long-term consequences need to be investigated in future studies.
Assuntos
Doenças do Recém-Nascido/etiologia , Apresentação no Trabalho de Parto , Segunda Fase do Trabalho de Parto/fisiologia , Doenças Metabólicas/etiologia , Complicações do Trabalho de Parto/etiologia , Índice de Apgar , Bases de Dados Factuais , Parto Obstétrico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Modelos Logísticos , Razão de Chances , Gravidez , Estudos Retrospectivos , Suécia , Artérias Umbilicais/químicaRESUMO
BACKGROUND AND OBJECTIVE: Tandem mass spectrometry-based newborn screening (NBS) is a powerful screening tool. The NBS process includes sample collection, shipment, testing, analysis, reporting and communication with the infant's family. We explored the NBS programme-related factors that may delay diagnosis and may influence timely initiation of treatment in neonates who present before the screening results are available and therefore urgently need diagnosis and treatment. STUDY DESIGN: Detailed retrospective review of all data regarding sampling, shipment, testing and notification, contact with family and initiation of treatment of all neonates with disorders of fatty acid oxidation (FAO) and protein metabolism (PM), who presented clinically before NBS results were available, between 1-February-2002 and 31-January-2014. RESULTS: Of 847,418 newborns screened, 18 infants presented clinically before NBS results were available (FAO n = 9, median age 2.5 days; PM n = 9, median age 3 days). Samples were collected from 11 infants at age 48-72 h, as per instructions, and were received in the laboratory at a median age of 7 days (median 4 days from sample collection until receipt in the laboratory). Results were available within 24h in 16/18 infants. Treatment for a suspected metabolic disorder was initiated in seven infants before results were available. CONCLUSIONS: An audit of the programme procedures enabled the identification of issues that can be improved. Some patients benefited from the availability of results shortly after presentation. Good communication between the laboratory, the clinical metabolic specialist service and the primary treating team ensures timely initiation of treatment in these infants.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo Lipídico/diagnóstico , Auditoria Médica , Triagem Neonatal/normas , Austrália , Carnitina/análogos & derivados , Carnitina/sangue , Feminino , Pessoal de Saúde/educação , Humanos , Recém-Nascido , Masculino , Triagem Neonatal/métodos , Estudos Retrospectivos , Espectrometria de Massas em Tandem , Fatores de TempoRESUMO
Our aim was to investigate the accuracy in predicting intrapartum fetal acidaemia and the interobserver reproducibility of a mathematical algorithm for the interpretation of electronic fetal heart rate (FHR) monitoring throughout labour. Eight physicians (blinded to the clinical outcomes of the deliveries) evaluated four randomly selected intrapartum FHR tracings by common visual interpretation, trying to predict umbilical artery base excess at birth. They subsequently were asked to re-evaluate the tracings using a mathematical algorithm for FHR tracing interpretation. Common visual interpretation allowed a correct estimation of the umbilical artery base excess in 34.4% of cases, with a poor interobserver reproducibility (Kappa correlation coefficient = 0.24). After implementation of the algorithm, the proportion of correct estimates significantly increased to 90.6% (p < 0.001), with excellent inter-clinician agreement (κ: 0.85). To conclude, incorporation of a standardised algorithm reduces the interobserver variability and allows a better estimation of fetal acidaemia at birth.
Assuntos
Acidose/diagnóstico , Algoritmos , Cardiotocografia , Trabalho de Parto/fisiologia , Adulto , Feminino , Frequência Cardíaca Fetal , Humanos , Recém-Nascido , Variações Dependentes do Observador , Parto/fisiologia , Gravidez , Método Simples-Cego , Adulto JovemRESUMO
BACKGROUND: In recent years it has become clear that newborn screening (NBS) programmes using tandem mass spectrometry identify "patients" with "classical" inborn errors of metabolism who are asymptomatic. This observation raises issues regarding medicalization of "non-diseases," potentially unnecessary treatment and unnecessary anxiety to parents. AIMS: This study aims to identify possible markers that may assist in predicting the need for treatment of infants with "classical" organic acidaemias (OA) and urea cycle disorders (UCD) diagnosed through NBS. METHODS: Medical records of all patients with classical OA and UCD detected through the Victorian NBS programme from February 2002 to January 2014, or diagnosed clinically between 1990 and January 2002 were retrospectively reviewed. RESULTS: Neonatal presentation did not always predict the need for on-going strict treatment. Blood concentrations of amino acids and acyl-carnitines and the changes thereof in follow-up samples correlated with severity in citrullinaemia-I, possibly isovaleric acidaemia but not in argininosuccinic aciduria or propionic acidaemia. Some specific mutations correlate with "attenuated" citrullinaemia-I. Gender may affect clinical outcome in propionic acidaemia. CONCLUSIONS: Changes in blood concentration of certain metabolites (amino acids, acyl-carnitines) in the first weeks of life may be predictive of the need for treatment in some disorders but not in others. Mutation analysis may be predictive in some disorders but whether or not this should be considered as second-tier testing in NBS should be discussed separately.
Assuntos
Triagem Neonatal , Distúrbios Congênitos do Ciclo da Ureia/genética , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Biomarcadores/metabolismo , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Mutação , Triagem Neonatal/métodos , Estudos Retrospectivos , Distúrbios Congênitos do Ciclo da Ureia/diagnóstico , Distúrbios Congênitos do Ciclo da Ureia/epidemiologia , Distúrbios Congênitos do Ciclo da Ureia/terapiaRESUMO
BACKGROUND: There is growing support for umbilical cord blood gas analysis (UCBGA) to be conducted at delivery. A recent study in a tertiary level obstetric unit found that universal UCBGA was associated with improved perinatal outcomes, but there is less evidence of benefit in lower-risk environments. In such settings, lactate analysis may be a suitable alternative. AIMS: This study evaluated the introduction of universal UCBGA into a secondary obstetric unit and universal umbilical cord lactate analysis program into primary and secondary units. METHODS: After education, universal UCBGA or lactate analysis was introduced into one primary and two secondary level obstetric units. Univariate and adjusted analysis assessed changes in UCBGA values and Apgar scores over the study period. RESULTS: There were no significant changes in mean blood gas and lactate values at any centre following introduction of universal UCBGA or lactate analysis. However, there was at the primary level obstetric unit a significant reduction in the proportion of neonates with moderate to severe elevations in umbilical artery lactate values. There was a non-significant reduction in arterial pH values less than 7.10 at the secondary metropolitan centre. CONCLUSION: The data presented in this study suggest that the benefits of introducing UCBGA into a tertiary obstetric centre may be reproduced in a primary obstetric centre within 12 months of implementation. Larger studies are required in secondary units to assess infrequent adverse obstetric and neonatal outcomes.
Assuntos
Gasometria , Sangue Fetal/química , Ácido Láctico/sangue , Acidose/diagnóstico , Adulto , Índice de Apgar , Parto Obstétrico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Fetal scalp lactate has been shown to be as effective as scalp pH in predicting fetal outcomes. However, there is limited clinical evidence to demonstrate a strong correlation with fetal acidaemia at birth. AIMS: To compare the diagnostic accuracy of fetal scalp lactate and umbilical cord arterial blood gas values sampling, as it is used in clinical practice. METHODS: A retrospective cohort study was performed on 661 term (≥37 weeks) births where a fetal scalp lactate sample was taken during labour. Cases were excluded where either the lactate was taken greater than 1 h prior to delivery, incomplete cord gas analyses were available, or a sentinel hypoxic event occurred prior to delivery. The final data set included 229 microvolume scalp lactate measurements which were compared with neonatal paired cord blood gas values taken at delivery. RESULTS: A fetal scalp lactate measurement of ≥4.8 mmol/L had a positive predictive value (PPV) of 1% and a negative predictive value (NPV) of 100% in predicting umbilical artery pH ≤7.00, and a PPV of 5% and a NPV of 98% in predicting umbilical artery pH ≤7.10. The sensitivity and specificity for these values were 100%, 23% and 90%, 23%, respectively. CONCLUSIONS: Fetal scalp lactate microsampling has a strong negative predictive value for fetal acidaemia at birth.
Assuntos
Acidose/diagnóstico , Gasometria , Sangue Fetal/química , Ácido Láctico/análise , Couro Cabeludo/química , Feminino , Monitorização Fetal , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Trabalho de Parto , Gravidez , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: . Neonatal screening of glutaric aciduria type 1 (GA-1) has brought radical changes in the course and outcomes of this disease. This study analyses the outcomes of the first 5 years (2015-2019) of the AGA1 neonatal screening programme in our autonomous community. MATERIAL: . We conducted an observational, descriptive and retrospective study. All neonates born between January 1, 2015 and December 31, 2019 that participated in the neonatal screening programme were included in the study. The glutarylcarnitine (C5DC) concentration in dry blood spot samples was measured by means of tandem mass spectrometry applying a cut-off point of 0.25⯵mol/L. RESULTS: . A total of 30 120 newborns underwent screening. We found differences in the C5DC concentration based on gestational age, type of feeding and hours of life at sample collection. These differences were not relevant for screening purposes. There were no differences between neonates with weights smaller and greater than 1500â¯g. Screening identified 2 affected patients and there were 3 false positives. There were no false negatives. The diagnosis was confirmed by genetic testing. Patients have been in treatment since diagnosis and have not developed encephalopathic crises in the first 4 years of life. CONCLUSIONS: . Screening allowed early diagnosis of two cases of GA-1 in the first 5 years since its introduction in our autonomous community. Although there were differences in C5DC levels based on gestational age, type of feeding and hours of life at blood extraction, they were not relevant for screening.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Encefalopatias Metabólicas , Glutaril-CoA Desidrogenase , Triagem Neonatal , Humanos , Triagem Neonatal/métodos , Recém-Nascido , Estudos Retrospectivos , Glutaril-CoA Desidrogenase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Masculino , Feminino , Encefalopatias Metabólicas/diagnóstico , Espectrometria de Massas em Tandem , Glutaratos/sangue , Idade Gestacional , Carnitina/análogos & derivadosRESUMO
Propionic acidaemia (PA) results from propionyl-CoA carboxylase deficiency. During metabolic decompensation, the accumulation of propionyl-CoA causes secondary hyperammonaemia through N-acetylglutamate synthetase inactivation. Carglumic acid, a structural analogue of N-acetylglutamate, was given to patients with PA (n=3) during episodes of metabolic decompensation (n=8; age range: birth to 4years), in addition to high energy/low protein intake and carnitine. Plasma ammonia concentrations normalised within 6-19h. Carglumic acid was well tolerated with no side effects noted.
Assuntos
Glutamatos/administração & dosagem , Hiperamonemia/tratamento farmacológico , Metilmalonil-CoA Descarboxilase/genética , Acidemia Propiônica/tratamento farmacológico , Erros Inatos do Metabolismo dos Aminoácidos , Amônia/sangue , Carnitina/sangue , Pré-Escolar , Feminino , Glutamatos/efeitos adversos , Humanos , Hiperamonemia/complicações , Hiperamonemia/patologia , Lactente , Recém-Nascido , Masculino , Metilmalonil-CoA Descarboxilase/metabolismo , Acidemia Propiônica/complicações , Acidemia Propiônica/patologiaRESUMO
Commercial 0.9% saline solution for infusion has a pH around 5.5. There are many reasons for this acidity, some of them still obscure. It is also true that infusion of normal saline can lead to metabolic acidaemia, yet the link between the acidity of saline solution and the acidaemia it can engender is not straightforward. This commentary draws together the known and putative sources of acidity in saline solutions: it turns out that the acidity of saline solution is essentially unrelated to the acidaemia complicating saline infusion.