The mitochondrial DNA depletion syndromes: mitochondrial DNA polymerase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
A diagnosis of mitochondrial DNA depletion may be suspected on the basis of fasting hypoglycemia and liver dysfunction characterized by elevations of gamma glutamyl transferase, often greater than alanine aminotransferase and aspartate aminotransferase, or by elevated creatine phosphokinase and ragged red fibers. Acquired mitochondrial DNA depletion syndromes have been described in adults as a complication of the treatment of HIV-1 and hepatitis B virus infections with the reverse transcriptase inhibitors azidothymidine and fluoriodoarauracil. Assay of purified mitochondria from skeletal muscle and liver revealed a complete absence of activity of mitochondrial DNA polymerase γ. Human DNA polymerase γ has been characterized as a reverse transcriptase. The cloning of the human mitochondrial DNA polymerase has facilitated molecular dissection. Avoidance of fasting is an important element in management of the hepatic forms of mitochondrial DNA depletion. Treatment of the nonhepatic forms of mitochondrial DNA depletion also includes carnitine and cofactor therapy.
Assessment of Tryptophan Metabolism and Vitamin B
A. S. Curry, J. V. Hewitt in Biochemistry of Women: Methods for Clinical Investigation, 1974
This chapter describes most of the methods that have been published for the determination of tryptophan metabolites in urine will be reviewed and selected procedures. The assessment of vitamin B 6 nutritional status will also be considered, with particular reference to urinary 4-pyridoxic acid and plasma pyridoxal phosphate determinations, and the use of erythrocyte alanine aminotransferase assays. The chapter discusses interpretation of the data obtained by these methods in pregnant and oral contraceptive treated women and an appraisal made of their clinical significance. Although studies of tryptophan metabolism have provided pointers toward this possibility, assessment of vitamin B 6 nutrition in women receiving these preparations also requires the application of methods which are not affected by enzyme induction or other hormonal effects. Interference with tryptophan metabolite analyses by drugs is of particular concern when colorimetric procedures are used in conjunction with ion-exchange chromatography.
Case 72
Vincent J Palusci, Dena Nazer, Patricia O Brennan in Diagnosis of Non-accidental Injury, 2015
A 4 year-old boy who was previously healthy was brought to the emergency department by the police. They were called by a neighbour who heard the boy screaming and crying. The boy disclosed that his mother’s boyfriend held him against the wall and punched him with his fist twice on his abdomen. He complains of abdominal pain. When you examine him, you note abdominal tenderness and multiple healed patterned marks on his abdomen (Image 72 ) and on his arms and legs. What does the image show? What tests and further imaging are important to evaluate this patient? 164 The image shows the left flank area and abdomen of the child. He has multiple patterned loop marks that have healed with hyperpigmentation. Loop marks result from being whipped with a cord or a belt and indicate this child has been physically abused. Although we cannot date when bruises originally occurred, these loop marks have healed so they must have occurred sometime before he was brought for medical care. 1 Children who disclose physical abuse need a detailed physical examination to further evaluate their presentation as well as document previous instances of abuse. Due to the child’s disclosure of being punched in the abdomen, he needs to be further evaluated for internal injuries. Blood was drawn for a complete blood count as well as liver and pancreatic enzymes. His liver enzymes were elevated: alanine aminotransferase (ALT) 866 U/L, aspartate transaminase (AST) 478 U/L. The normal range for ALT is reported between 7 and 56 units per litre and for AST between 10 and 40 units per litre. It is recommended that children with transaminases levels >80 U/L should undergo definitive testing for abdominal injury in cases where physical abuse is suspected as in this child. 2 A CT scan of his abdomen showed a small liver laceration with mild periportal oedema as well as retroperitoneal fluid collection between the aorta and inferior vena cava. Due to the fluid collection an upper gastrointestinal series with barium as a contrast was done which showed thickened duodenal folds, which may be due to oedema secondary to the patient’s history of trauma. An exploratory laparotomy was performed which confirmed the contusion of the liver. It also revealed contusions of the transverse colon and duodenum. This case highlights the importance of a full evaluation of children disclosing physical abuse. Children need to be screened for abdominal trauma initially with liver enzymes. Abdominal trauma is the second most common cause of death from abuse and needs to be recognized in a timely manner. However, children may have significant abdominal trauma with mild symptoms as in this case and with few or no physical findings on exam.
Paralytic ileus in the patient with tuberculosis of spine
Published in British Journal of Neurosurgery, 2020
Viskasari P. Kalanjati, Rury T. Oktariza, Yahya Yahya, Abdulloh Machin
Background: We reported a patient with spinal tuberculosis and paralytic ileus. A 56-year-old Javanese male presented with lower limb paralysis and bowel obstruction 2 weeks prior to admission. He was found to have hypoalbuminemia and hypesthesia from the T7/T9 levels and below. Other than increased alanine aminotransferase, hematology and blood chemical tests were normal. MRI and plain abdominal radiographs confirmed the diagnosis of spinal tuberculosis at the T5/6 level and paralytic ileus. Tubercles in the lymphoid tissue of the intestinal submucosa were not seen. Conclusion: Paralytic ileus may occur in spinal TB.
Hepatotoxicity after paracetamol overdose in a patient with cystic fibrosis despite early acetylcysteine and utility of microRNA to predict hepatotoxicity
Published in Clinical Toxicology, 2018
Anselm Wong, Benjamin Cheung, Charlotte Nejad, Michael Gantier, Andis Graudins
Case details: A 19-year-old girl presented to the emergency department following overdose of 10 g of paracetamol on a background history of cystic fibrosis. Paracetamol concentration was below the nomogram line, but was treated with acetylcysteine seven hours post-overdose given her symptomatology. Nineteen hours following her overdose she developed hepatotoxicity, despite early initiation of acetylcysteine. She was discharged well six days post-ingestion. On presentation, delta miRNA-122-miR483 was 20 times that of control patients, however, alanine aminotransferase was normal. Discussion: Patients with cystic fibrosis are more likely to have glutathione deficiency, and greater susceptibility to liver injury. Delta miRNA may be a better detector of early liver injury than hepatic aminotransferases. Empiric treatment with acetylcysteine and serial biochemical reassessment in this setting should be considered.
Effect of rutin on proinflammatory cytokines and oxidative stress in toxin-mediated hepatotoxicity
Published in Toxin Reviews, 2018
Noura AlDrak, Manal Abudawood, Sherifa S. Hamed, Sabah Ansar
The present study was designed to evaluate the effect of rutin (RT) on lead (Pb)-induced oxidative stress. Rats were divided into groups and were treated with RT with or without lead. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were evaluated. Levels of AST, ALT, TNF-α, IL-6, and IL-1β were significantly decreased, and the activities of antioxidant enzymes were increased in the liver of rats treated with RT along with Pb. Histologic changes were improved to almost a normal hepatic structure. The results suggest that RT controls the damaged antioxidant status in Pb-induced oxidative stress.
Related Knowledge Centers
- Chronotype
- Transaminases
- Liver
- Blood Plasma
- Ec
- Alanine Cycle
- Liver Function Tests