China
Africa
Explore chapters and articles related to this topic
Maple Syrup Urine Disease (MSUD)
Published in Charles Theisler, Adjuvant Medical Care, 2023
Maple syrup urine disease is an inherited disorder that affects branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor that emanates from an affected infant's urine. This disorder is
Introduction to the organic acidemias
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Initial laboratory evaluation involves tests that are readily available in most clinical chemistry laboratories. Most important in early discrimination are the electrolytes and the ammonia. Blood gases are often the first data available in a very sick infant. Acidosis and hyperammonemia are indicative of an organic acidemia. In contrast, a patient with a urea cycle defect has hyperammonemia and alkalosis. It is important not to delay treatment of acidosis in the belief that the problem is a urea cycle defect. Hyperammonemia regardless of cause must be treated. Hypocalcemia may be a nonspecific harbinger of metabolic disease. Elevated levels of lactate in the absence of cardiac disease, shock or hypoxemia are often seen in organic acidemias as well as in the lactic acidemias of mitochondrial disease. The blood count is useful in indicating the presence or absence of infection. More important, neutropenia with or without thrombocytopenia or even with pancytopenia is characteristic of organic acidemia.
Hereditary and Metabolic Diseases of the Central Nervous System in Adults
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Emergency treatment for a suspected intoxication-type metabolic disorder consists of reversing catabolism and removing toxic compounds, as well as supporting the affected metabolic pathway by reducing precursors to the pathway, replacing any deficient compounds, and providing cofactors. As metabolic genetics recommendations are not always immediately available, the clinical team should consider starting initial neuroprotective treatment with glucose. The life-saving intervention in many cases is starting continuous intravenous (IV) glucose (dextrose) infusion at 6–8 mg/kg/min in normal saline or other solution with appropriate electrolytes and no lactate. This is applicable to both patients with hyperammonemia (suspected urea cycle disorders) or with high anion gap metabolic acidosis (suspected organic acidemias). The purpose of the glucose is to reverse catabolism by providing energy for cells to use, so the glucose is started and kept at the same rate regardless of the patient's actual glucose level. If the patient becomes hyperglycemic, an insulin drip should be titrated to maintain normoglycemia without decreasing the glucose dose or rate. Treatments for hyperammonemia depend on the ammonia level and include ammonia scavenger medications that conjugate to ammonia for excretion in urine (sodium phenylacetate–sodium benzoate) and dialysis. Further treatment depends on the suspected disorder but may involve temporarily reducing or stopping protein intake while providing sufficient nutrition to avoid catabolism, carnitine (which conjugates to toxic organic acids in organic acidemias), and specific cofactors or other medication treatment. Future episodes of acute encephalopathy can be prevented in many of these disorders by the combination of long-term dietary and medication treatment with “sick-day management.” Whenever patients are exposed to physiological stressors including viral illnesses or fasting for planned surgery, dietary alterations to preempt the accumulation of toxic compounds are made, such as increased caloric intake, decreased protein, or increased medication doses. A patient who is scheduled to fast for surgery may be admitted early for parenteral nutrition, while a patient who develops symptoms of a viral illness may be given recommendations for treatment at home and admission to the hospital if symptoms of metabolic intoxication such as vomiting develop.
Two cases of glutaric aciduria type II: how to differentiate from inflammatory myopathies?
Published in Acta Clinica Belgica, 2019
Meltem Koca, Abdulsamet Erden, Berkan Armagan, Alper Sari, Fatih Yildiz, Sevim Ozdamar, Umut Kalyoncu, Omer Karadag
The clinical presentation is heterogeneous and can be grouped into three forms: the neonatal-onset form with and without congenital anomalies (type 1 and 2, respectively), and the late-onset form (type 3) [1]. Severity of the clinical picture is not related to the gene which is affected (ETFA, ETFB or ETFDH), rather it depends on the nature and the location of the mutation [2]. The neonatal-onset forms are usually fatal in perinatal period and present with acute metabolic decompensations characterized by severe metabolic acidosis, nonketotic hypoglycemia, hypotonia, multisystem involvement with or without congenital anomalies which include facial dysmorphism, cystic renal dysplasia, and cerebral malformations and even coma [3]. Age and symptoms at presentation are highly variable in the late onset form and are characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and chronic manifestations of lipid storage myopathy: myalgia, muscle weakness and exercise intolerance. Organic aciduria may be mild, atypical, or detectable only during acute metabolic decompensations [4].
The potential role of gut microbiota and its modulators in the management of propionic and methylmalonic acidemia
Published in Expert Opinion on Orphan Drugs, 2018
Alberto Burlina, Sebastian Tims, Francjan van Spronsen, Wolfgang Sperl, Alessandro P. Burlina, Mirjam Kuhn, Jan Knol, Maryam Rakhshandehroo, Turgay Coşkun, Rani H Singh, Anita MacDonald
Constipation appears to commonly precede decompensation, which could be due to increased time of bacterial contact with the stool in the gut. Changes in gut motility may be one of many factors contributing to constipation in PA/MMA. Other causal factors include unusual diet, synthetic formulas, developmental delays, patient hypomobility, and muscle hypotonia [14,35]. Constipation may be aggravated by inadequate fluid intake in children with organic acidemias [35–37]. For example, a single-center study showed fluid intake provided only 80% of the daily requirements for age [35]. In addition, low fiber intake among patients with PA/MMA on nutritionally restricted diets is associated with constipation and could alter the composition of gut microbiota. Although evidence is limited, fiber intake is low in patients with organic acidemias and one study reported a median of only 4 g/day in tube-fed children [35,36].
De novo mutation in SLC25A22 gene: expansion of the clinical and electroencephalographic phenotype
Published in Journal of Neurogenetics, 2021
Antonio Gennaro Nicotera, Daniela Dicanio, Erica Pironti, Maria Bonsignore, Anna Cafeo, Stephanie Efthymiou, Patrizia Mondello, Vincenzo Salpietro, Henry Houlden, Gabriella Di Rosa
OS is a rare and severe disease affecting infants within the first 3 months of life. Tonic spasms are the most common seizures and can occur as a cluster or single episodes and be refractory to treatment. Focal and myoclonic seizures can also occur. The electroencephalogram (EEG) is characterized by a burst-suppression pattern both in waking and sleeping states (Mastrangelo & Leuzzi, 2012). OS phenotype caused by SLC25A22 mutations mostly overlaps with other OS forms associated with other genes’ mutations (i.e.: CDKL5 or ARX) (Sartori et al., 2011). It is featured by myoclonic seizures within the first month of life and late-onset tonic spasms, hypotonia, microcephaly, abnormal visual evoked potential (VEP), and electroretinogram (Mastrangelo & Leuzzi, 2012). EME is a rare epileptic encephalopathy characterized by erratic myoclonus and refractory partial seizures with neonatal or early infantile-onset and suppression-burst EEG pattern during sleep. EME may be caused by metabolic disorders, such as non-ketotic hyperglycinemia and organic acidemias, or genetic disorders due to mutations in ERBB4, SIK1, SLC25A22, KCNQ2 and GABRB2 genes (Giacomini et al., 2019; Mastrangelo & Leuzzi, 2012). MMPSI is a severe and rare epileptic encephalopathy. EEG abnormalities involve different regions of the brain, migrating from one region to another one and leading to focal seizures, which are typically multifocal, independent, and drug-resistant. To date, KCNT1, PLCB1, SCN1A, SCN8A, TBC1D24 and SLC25A22 are the genes associated with MMPSI (Poduri et al., 2013; Striano, Coppola, Zara, & Nabbout, 2014).