MNGIE Syndrome: Liver Cirrhosis Should Be Ruled Out Prior to Bone Marrow Transplantation

Finkenstedt, Armin; Schranz, Melanie; Bösch, Sylvia; Bürgi, Sabine Scholl; Ensinger, Christian; Drach, Mathias; Mayr, Johannes A.; Janecke, Andreas R.; Vogel, Wolfgang; Nachbaur, David; Zoller, Heinz

doi:10.1007/8904_2012_199

Cited by 18 publications

(17 citation statements)

References 11 publications

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“…Permanent tissue replacement of TP is currently considered the best treatment to recover TP activity and reduce nucleoside imbalance. 12 Given that MNGIE patients may develop liver failure 19 and considering that OLT shows a high survival rate (85-95%), 20 the liver appeared to be the ideal organ for transplantation aimed at stably rescuing TP activity. Also, the "end-stage" illness of patients who underwent AHSCT represented a risk factor to a poor outcome.…”

Section: Discussionmentioning

confidence: 99%

Liver transplantation for mitochondrial neurogastrointestinal encephalomyopathy

Giorgio

Pironi

Rinaldi

et al. 2016

Annals of Neurology

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Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal, recessive disease caused by mutations in the gene encoding thymidine phosphorylase, leading to reduced enzymatic activity, toxic nucleoside accumulation, and secondary mitochondrial DNA damage. Thymidine phosphorylase replacement has been achieved by allogeneic hematopoietic stem cell transplantation, a procedure hampered by high mortality. Based on high thymidine phosphorylase expression in the liver, a 25-year-old severely affected patient underwent liver transplantation. Serum levels of toxic nucleosides rapidly normalized. At 400 days of follow-up, the patient's clinical conditions are stable. We propose liver transplantation as a new therapy for MNGIE. Ann Neurol 2016;80:448-455.

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Section: Discussionmentioning

confidence: 99%

Liver transplantation for mitochondrial neurogastrointestinal encephalomyopathy

Giorgio

Pironi

Rinaldi

et al. 2016

Annals of Neurology

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“…The neurological symptoms also vary from case to case, and may include paraesthesia, numbness, pain in the limbs, symmetric and distal muscle weakness, hearing loss and ocular symptoms. Neuropathic pain is treated with centrally acting agents such as amitriptyline, gabapentin and pregabalin [41,79] . Physiotherapy and occupational therapy may be required, according to the needs of the patient [80] .…”

Section: Symptomatic Therapiesmentioning

confidence: 99%

“…Patients with MNGIE are likely to present a higher risk of developing gut graft versus host disease because of the disease-related gastrointestinal damage. Disease-related hepatopathies, including hepatic steatosis, hepatomegaly, increased transaminases, abnormal liver function, triglyceride hyperlipidaemia and cirrhosis, have been reported in MNGIE and thus the presence of liver disease should be established prior to transplantation [16,79] . The use of parental nutrition and the long-term effect this is likely to have on the liver should also be considered.…”

Section: Ahsctmentioning

confidence: 99%

“…Patients with MNGIE often have disease-related hepatopathies, and, considering that OLT has a high survival rate, this approach presents an ideal solution to simultaneously rescue thymidine phosphorylase activity and replace a diseased liver. However, the administration of parenteral nutritional support post-transplant should be carefully considered due to the association of its use with hepatic steatosis and elevated transaminases [79] . OLT is limited by the availability of matched donors and can potentially present risks from transplantation complications and the use of long-term immunosuppression therapy.…”

Section: Oltmentioning

confidence: 99%

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Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment

Bax¹

2019

JTGG

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Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disease caused by mutations in TYMP, the gene encoding for the enzyme thymidine phosphorylase. The resulting enzyme deficiency leads to a systemic accumulation of thymidine and 2'-deoxyuridine and ultimately mitochondrial failure due to a progressive acquisition of secondary mitochondrial DNA (mtDNA) mutations and mtDNA depletion. MNGIE is characterised by gastrointestinal dysmotility, cachexia, peripheral neuropathy, ophthalmoplegia, ptosis and leukoencephalopathy. The disease is progressively degenerative and leads to death at an average age of 37.6 years. Patients invariably encounter misdiagnoses, diagnostic delays, and non-specific clinical management. Despite its rarity, MNGIE has invoked much interest in the development of therapeutic strategies, mainly because it is one of the few mitochondrial disorders where the molecular abnormality is metabolically and physically accessible to manipulation. This review provides a résumé of the current diagnosis and treatment approaches and aims to increase the clinical awareness of MNGIE and thereby facilitate early diagnosis and timely access to treatments, before the development of untreatable and irreversible organ damage.

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“…GFM1 mutation, Leigh disease and mitochondrial neurogastrointestinal encephalopathy syndrome, so called MNGIE syndrome, are such examples. [65][66][67]…”

Section: Myopathic Disordersmentioning

confidence: 99%

Paediatric fatty liver disease (PeFLD): All is not NAFLD – Pathophysiological insights and approach to management

Hegarty

Deheragoda

Fitzpatrick

et al. 2018

Journal of Hepatology

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The recognition of a pattern of steatotic liver injury where histology mimicked alcoholic liver disease, but alcohol consumption was denied, led to the identification of non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease has since become the most common chronic liver disease in adults owing to the global epidemic of obesity. However, in paediatrics, the term NAFLD seems incongruous: alcohol consumption is largely not a factor and inherited metabolic disorders can mimic or co-exist with a diagnosis of NAFLD. The term paediatric fatty liver disease may be more appropriate. In this article, we summarise the known causes of steatosis in children according to their typical, clinical presentation: i) acute liver failure; ii) neonatal or infantile jaundice; iii) hepatomegaly, splenomegaly or hepatosplenomegaly; iv) developmental delay/psychomotor retardation and perhaps most commonly; v) the asymptomatic child with incidental discovery of abnormal liver enzymes. We offer this model as a means to provide pathophysiological insights and an approach to management of the ever more complex subject of fatty liver.

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MNGIE Syndrome: Liver Cirrhosis Should Be Ruled Out Prior to Bone Marrow Transplantation

Cited by 18 publications

References 11 publications

Liver transplantation for mitochondrial neurogastrointestinal encephalomyopathy

Liver transplantation for mitochondrial neurogastrointestinal encephalomyopathy

Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment

Paediatric fatty liver disease (PeFLD): All is not NAFLD – Pathophysiological insights and approach to management

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