Use of Amnion Epithelial Cells in Metabolic Liver Disorders
Ornella Parolini, Antonietta Silini in Placenta, 2016
Inborn errors of metabolism usually arise from a single enzymatic defect. Abnormal storage or use of proteins, carbohydrates, lipids, or other nutrients account for a large part of the metabolic diseases. Inborn errors of metabolism can be categorized as follows: Disease generated by deficient hepatocytes resulting in liver-specific pathology (i.e., Crigler–Najjar syndrome)Disease generated by deficient hepatocytes leading to extrahepatic complications (i.e., alpha-1 antitrypsin [A1AT] deficiency)Disease generated extrahepatically, whose pathological manifestation results within the liver (i.e., hemochromatosis)
Genetics
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
Important note: many disorders of mitochondrial function are caused by mutations in nuclear genes and show AR inheritance. Natural history: progressive conditions. Prognosis depends on the diagnosis and age of presentation.Differential diagnosis: clinical overlap with inborn errors of metabolism.Treatment/Management/Surveillance: management and care should be provided by a neurologist or a metabolic physician. Family members require specialist genetic counselling because of the complexities of estimating risks to another pregnancy, and prenatal testing.
Inborn errors of metabolism
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
From the viewpoint of genetic counselling, inborn errors of metabolism have several characteristics that must be taken into account: Almost all follow a Mendelian recessive pattern of inheritance, the great majority being autosomal.Precise molecular and/or biochemical techniques for early recognition, carrier detection and prenatal diagnosis are often available, although the biochemical methods (such as enzyme assays) may be confined to a very few expert centres. Molecular genetic methods are generally much more robust and so are usually preferred as long as the causal gene variant is known with certainty.Genetic heterogeneity in terms of multiple loci is frequent but can usually be resolved with appropriate investigations, if not clinically. Further redefinition of apparently well-defined disorders will undoubtedly continue.
Biochemical screening of intellectually disabled and healthy children in Punjab, Pakistan: differences in liver function test and lipid profiles
Published in International Journal of Developmental Disabilities, 2020
Muhammad Wasim, Haq Nawaz Khan, Hina Ayesha, Fazli Rabbi Awan
Inborn errors of metabolism are rare genetic disorders, and several of them cause intellectual disability in children. Therefore, in this study, we have investigated clinically important biochemical parameters in healthy and suspected IEM children with intellectual disability in Pakistan to find out any association among such parameters with the intellectual disability. In our collected samples, we have found that several biochemical parameters were significantly different in patient samples as compared to healthy samples. Elevated level of ALP has already been reported in different metabolic conditions like obesity and Wilson disease patients. In this study, levels of ALP, ASAT, ALAT, albumin, hemoglobin, and uric acid were found significantly different as compared to healthy children. Some of the intellectually disabled patients in this study also had high levels of cholesterol and triglyceride and are suspected for hyperlipidemia. Consequently, intellectually disabled patients might have been associated with the high levels of above mentioned parameters, but further research is needed to confirm this finding. Moreover, advance analytical tools like HPLC, GC, GC-MS, LC-MS/MS, PCR, and DNA sequencing etc. are needed for the earlier diagnosis and treatment of IEMs in Pakistani patients. Finally, this study will help to initiate a NBS program in Pakistan for the screening of different inherited metabolic disorders, which can help the affected patients to live a healthy life.
Contemporary surgical management of drug-resistant focal epilepsy
Published in Expert Review of Neurotherapeutics, 2020
Jasmina R. Milovanović, Slobodan M. Janković, Dragan Milovanović, Dejana Ružić Zečević, Marko Folić, Marina Kostić, Goran Ranković, Srđan Stefanović
If epilepsy surgery is to be planned, precise etiology of epilepsy observed in the patients should be elucidated. Causes of epilepsy could be classified to six categories according to prevailing underlining pathology: metabolic, genetic, infectious, immune, developmental anomalies, and unknown [6]. However, not all of them are amenable for surgical treatment, especially when pathological process either causes multiple focal lesions or would continue even after surgery, making new focal lesions. Disorders of metabolic pathways with piling up or deficiency of certain intermediate metabolic products may disturb membrane potential of neurons and result with seizures. The disorders are usually linked to an inborn error of metabolism, caused by a genetic defect that was inherited. Some of the most frequent metabolic causes of epilepsy are Menkes syndrome (decreased ingress of copper to neurons due to deficiency of a membrane transport protein), biotinidase deficiency (resulting with biotin deficit) [7], neuronal ceroid lipofuscinosis (accumulation of neuronal and extra neuronal lipopigments) [8], sphingolipidoses (lysosomal lipid storage disorders), mitochondrial disorders (mitochondrial dysfunction), sulfite oxidase deficiency (accumulation of sulfur-containing amino acids in neurons) [9], and serine biosynthesis defects (causing serine deficiency in neurons, so many functional proteins cannot be synthesized).
Congenital central hypoventilation syndrome: diagnosis and management
Published in Expert Review of Respiratory Medicine, 2018
Melissa A. Maloney, Sheila S. Kun, Thomas G. Keens, Iris A. Perez
CCHS should be considered in infants and children with hypoventilation that is most severe during sleep in the absence of underlying pulmonary, cardiac, neuromuscular, or metabolic conditions. Children with a suspected diagnosis of CCHS should undergo genetic testing for PHOX2B gene mutations [1,15]. Patients should be evaluated for other causes of hypoventilation. Polysomnogram is particularly important in evaluating for sleep hypoventilation and the presence of other sleep-related breathing disorders and should be performed in accordance with the most current version of the American Academy of Sleep Medicine guidelines [67]. During polysomnogram, noninvasive methods of monitoring oxygenation and ventilation are preferred over intermittent blood gas analysis, as sampling leads to patient arousal and does not reflect the true sleep state. Additional workup should include chest radiograph, electrocardiogram to evaluate for rhythm abnormalities, and echocardiogram to evaluate for pulmonary hypertension and cor pulmonale. In some cases, chest CT to evaluate for primary lung disease, MRI and/or CT scan of the brain and brainstem to evaluate for anatomic lesions, and comprehensive neurologic assessment to rule out neuromuscular disease may be useful, but these studies are not part of routine CCHS evaluation at our institution [1]. Laboratory evaluation for inborn errors of metabolism should be considered in patients who have not undergone comprehensive newborn screening.
Related Knowledge Centers
- Biochemistry
- Birth Defect
- Enzyme
- Organic Acid
- Amino Acid
- Carbohydrate
- Genetic Disorder
- Gene
- Substrate
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