Publications by authors named "Ellen Johanne Annexstad"

2 Publications

  • Page 1 of 1

Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug-metabolizing enzymes.

Basic Clin Pharmacol Toxicol 2020 Jul 5;127(1):47-51. Epub 2020 Feb 5.

Norwegian National Unit for CBRNE Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Paracetamol has a good safety profile, but pharmacogenetic differences in drug-metabolizing enzymes may have an impact on its risk of hepatotoxicity. We present a case of fatal acute liver failure (ALF) after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy, where pharmacogenetic screening was conducted. This 30-year-old man was electively admitted for a tracheostomy. A total of 14.5 g paracetamol was given over four days. He developed a severe ALF and died 11 days after admission. Pharmacogenetic screening showed absent CYP2D6 metabolism and increased CYP1A2 activity, which may have increased the formation of toxic intermediate metabolite, N-acetyl-p-benzo-quinone imine (NAPQI). He also had decreased function of UGT2B15, which increases the amount of paracetamol available for metabolism to NAPQI. Having a reduced muscle mass and thus a reduced glutathione levels to detoxify produced NAPQI may add to the risk of toxicity. This case may indicate that pharmacogenetic variability is of potential relevance for the risk of paracetamol-induced hepatotoxicity in patients with neuromuscular diseases. Further studies should investigate if pharmacogenetic screening could be a tool to detect potentially increased risk of hepatotoxicity in these patients at therapeutic doses of paracetamol and hence provide information for selection of analgesic treatment.
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July 2020

Molecular and Clinical Characteristics of a National Cohort of Paediatric Duchenne Muscular Dystrophy Patients in Norway.

J Neuromuscul Dis 2019 ;6(3):349-359

Oslo University Hospital, Unit for Congenital and Inherited Neuromuscular Disorders, Oslo, Norway.

Background: As new gene-related treatment options for Duchenne muscular dystrophy (DMD) are being developed, precise information about the patients' genetic diagnosis and knowledge about the diversities of natural history in DMD is vital.

Objective: To obtain detailed insight into the genetic and clinical characteristics of paediatric DMD in Norway.

Methods: 94 boys with DMD, aged 0-18 years, were identified over a period of 3.5 years, yielding a national prevalence of 13.5×10-5 boys. 73 boys (78%) were recruited to full genetic and clinical or limited (genetic only) evaluation.

Results: Molecular analysis disclosed 64% deletions, 18% duplications and 18% point mutations. The mean age of diagnosis was 3.9±2.0 years. 78% were treated with glucocorticoids from age 5.8±1.5 years. 23 boys (35%) had lost ambulation at an age of 10.7±2.0 years. 17% were treated for left ventricular dysfunction from age 12.1±3.0 years and 12% had received night-time non-invasive positive pressure ventilation from age 13.0±2.5 years.

Conclusions: The distribution of mutation types and sites was similar to previous studies but with more duplications and fewer point mutations. Any genotype-phenotype correlations were not uncovered. The boys were diagnosed early but there is still diagnostic delay among boys presenting with late motor development. Glucocorticoid treatment was widespread, especially among the younger boys. The clinical results of this comprehensive nationwide study highlight the large variability of disease progression in DMD.
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February 2020