Clinical, biochemical and morphological features of hepatocerebral syndrome with mitochondrial DNA depletion due to deoxyguanosine kinase deficiency

Labarthe, François; Dobbelaere, Dries; Devisme, Louise; Muret, A. De; Jardel, Claude; Taanman, Jan‐Willem; Gottrand, Frédéric; Lombès, Anne

doi:10.1016/j.jhep.2005.03.023

Cited by 82 publications

(87 citation statements)

References 23 publications

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“…A minority of affected individuals present initially in infancy or childhood with isolated hepatic disease, occasionally following a viral illness. Affected individuals with this form may develop mild hypotonia and renal involvement manifesting as proteinuria and aminoaciduria [2,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]. More recently, DGUOK mutations have been reported in a neonate with clinical and autopsy findings consistent with neonatal hemochromatosis and mtDNA depletion [56], and in individuals with adult-onset mitochondrial myopathy and mtDNA multiple deletions in skeletal muscle [57].…”

Section: Dguok-related Hepatocerebral Mdsmentioning

confidence: 99%

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Mitochondrial DNA Depletion Syndromes: Review and Updates of Genetic Basis, Manifestations, and Therapeutic Options

2013

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Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a genetically and clinically heterogeneous group of autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs. MDS are due to defects in mtDNA maintenance caused by mutations in nuclear genes that function in either mitochondrial nucleotide synthesis (TK2, SUCLA2,

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Section: Dguok-related Hepatocerebral Mdsmentioning

confidence: 99%

“…Liver histopathology typically reveals microvesicular cholestasis, but may show bridging fibrosis, giant cell hepatitis, or cirrhosis. Liver electron microscopy may reveal an increase in the number of mitochondria and is commonly associated with abnormal cristae [40,45,54,55,58].…”

Section: Dguok-related Hepatocerebral Mdsmentioning

confidence: 99%

Mitochondrial DNA Depletion Syndromes: Review and Updates of Genetic Basis, Manifestations, and Therapeutic Options

2013

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“…A wide range of abnormal liver histologies can be produced by mitochondrial disease [105,106]. Isolated COX deficiency in respiratory chain biochemical testing can be seen in disease caused by any of the 5 nuclear genes listed above.…”

Section: Liver Analysismentioning

confidence: 99%

The in-depth evaluation of suspected mitochondrial disease

Haas

Parikh

Falk

et al. 2008

Molecular Genetics and Metabolism

318

300

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Mitochondrial disease confirmation and establishment of a specific molecular diagnosis requires extensive clinical and laboratory evaluation. Dual genome origins of mitochondrial disease, multiorgan system manifestations, and an ever increasing spectrum of recognized phenotypes represent the main diagnostic challenges. To overcome these obstacles, compiling information from a variety of diagnostic laboratory modalities can often provide sufficient evidence to establish an etiology. These include blood and tissue histochemical and analyte measurements, neuroimaging, provocative testing, enzymatic assays of tissue samples and cultured cells, as well as DNA analysis. As interpretation of results from these multifaceted investigations can become quite complex, the Diagnostic Committee of the Mitochondrial Medicine Society developed this review to provide an overview of currently available and emerging methodologies for the diagnosis of primary mitochondrial disease, primarily focusing on disorders characterized by impairment of oxidative phosphorylation. The aim of this work is to facilitate the diagnosis of mitochondrial disease by geneticists, neurologists, and other metabolic specialists who face the challenge of evaluating patients of all ages with suspected mitochondrial disease.

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“…We have found this mutation in several control chromosomes in a heterozygous state. References: Freisinger (Freisinger, et al, 2006) Labarthe (Labarthe, et al, 2005) Mancuso a (Mancuso, et al, 2003) Mancuso b (Mancuso, et al, 2005) Mandel Mousson (Mousson de Camaret, et al, 2007) Salviati (Salviati, et al, 2002) Sarzi, Slama (Slama, et al, 2005a) Taanman (Taanman, et al, 2002) Tadiboyina (Tadiboyina, et al, 2005) Wang …”

Section: Patient Ethnicity Sexmentioning

confidence: 99%

“…Early liver transplant appears to be effective in patients with isolated liver involvement (Freisinger, et al, 2006;Labarthe, et al, 2005). One patient, with stable liver synthetic function from one year of age, has survived to 10 years of age with only supportive care (Mousson de Camaret, et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase

Dimmock¹,

Zhang²,

et al. 2008

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Published mutations in deoxyguanosine kinase (DGUOK) cause mitochondrial DNA depletion and a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia. In this series, we have identified 15 different mutations in the DGUOK gene from 9 kindreds. Among them, 12 have not previously been reported. Nonsense, splice site, or frame-shift mutations that produce truncated proteins predominate over missense mutations. All patients who harbor null mutations had early onset liver failure and significant neurological disease. These patients have all died before 2-years of age. Conversely, two patients carrying missense mutations had isolated liver disease and are alive in their 4th year of life without liver transplant. Five subjects were detected by newborn screening, with elevated tyrosine or phenylalanine. Consequently, this disease should be considered if elevated tyrosine is identified by newborn screening. Mitochondrial DNA content was below 10% of controls in liver in all but one case and modestly reduced in blood cells. With this paper a total of 39 different mutations in DGUOK have been identified. The most frequent mutation, c.763_c.766dupGATT, occurs in 8 unrelated kindreds. 70% of mutations occur in only one kindred, suggesting full sequencing of this gene is required for diagnosis. The presentation of one case with apparent viral hepatitis, without neurological disease, suggests that this disease should be considered in patients with infantile liver failure regardless of the presence of neurological features or apparent infectious etiology.

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Clinical, biochemical and morphological features of hepatocerebral syndrome with mitochondrial DNA depletion due to deoxyguanosine kinase deficiency

Cited by 82 publications

References 23 publications

Mitochondrial DNA Depletion Syndromes: Review and Updates of Genetic Basis, Manifestations, and Therapeutic Options

Mitochondrial DNA Depletion Syndromes: Review and Updates of Genetic Basis, Manifestations, and Therapeutic Options

The in-depth evaluation of suspected mitochondrial disease

Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase

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