Clinical variability in neurohepatic syndrome due to combined mitochondrial DNA depletion and Gaucher disease

Harvengt, Julie; Wanty, Catherine; Paepe, Boél De; Sempoux, Christine; Revençu, Nicole; Smet, Joél; Coster, Rudy Van; Lissens, Willy; Seneca, Sara; Weekers, Laurent; Sokal, Étienne; Debray, François-Guillaume

doi:10.1016/j.ymgmr.2014.04.006

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…Recently consanguineous siblings with both mtDNA depletion and Gaucher disease were reported [11]. The family had three children diagnosed with Gaucher disease, which was confirmed biochemically as well as by the detection of a homozygous mutation in the GBA gene.…”

Section: Discussionmentioning

confidence: 69%

A SUCLG1 mutation in a patient with mitochondrial DNA depletion and congenital anomalies

Landsverk

Zhang

Wong

et al. 2014

Molecular Genetics and Metabolism Reports

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Defects in two subunits of succinate-CoA ligase encoded by the genes SUCLG1 and SUCLA2 have been identified in mitochondrial DNA (mtDNA) depletion syndromes. Patients generally present with encephalomyopathy and mild methylmalonic acidemia (MMA), however mutations in SUCLG1 normally appear to result in a more severe clinical phenotype. In this report, we describe a patient with fatal infantile lactic acidosis and multiple congenital anomalies (MCAs) including renal and cardiac defects. Molecular studies showed a defective electron transport chain (ETC), mtDNA depletion, and a novel homozygous mutation in the SUCLG1 gene. Although our patient's clinical biochemical phenotype is consistent with a SUCLG1 mutation, it is unclear whether the MCAs observed in our patient are a result of the SUCLG1 mutation or alterations in a second gene. An increasing number of reports have described MCAs associated with mitochondrial disorders and SUCLG1 specifically. Additional studies such as whole exome sequencing will further define whether additional genes are responsible for the observed MCAs.

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Section: Discussionmentioning

confidence: 69%

A SUCLG1 mutation in a patient with mitochondrial DNA depletion and congenital anomalies

Landsverk

Zhang

Wong

et al. 2014

Molecular Genetics and Metabolism Reports

View full text Add to dashboard Cite

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“…Aggregates of α-synuclein within mitochondria may impair the function of this organelle [111]. There were reductions in the activities of the mitochondrial complexes I-III in patient-cultured fibroblasts (complex IV was not examined) [126], and a decrease in complex IV (cytochrome C oxidase) was observed in a liver of a patient, likely with type 3 disease [127]. Multiple indicators of mitochondrial health and function in the brain were decreased in models of Gaucher's disease [114,128].…”

Section: Gaucher's Disease-a Deficiency Of Glucosylceramidasementioning

confidence: 99%

Examining the Role of a Functional Deficiency of Iron in Lysosomal Storage Disorders with Translational Relevance to Alzheimer’s Disease

LeVine

2023

Cells

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The recently presented Azalea Hypothesis for Alzheimer’s disease asserts that iron becomes sequestered, leading to a functional iron deficiency that contributes to neurodegeneration. Iron sequestration can occur by iron being bound to protein aggregates, such as amyloid β and tau, iron-rich structures not undergoing recycling (e.g., due to disrupted ferritinophagy and impaired mitophagy), and diminished delivery of iron from the lysosome to the cytosol. Reduced iron availability for biochemical reactions causes cells to respond to acquire additional iron, resulting in an elevation in the total iron level within affected brain regions. As the amount of unavailable iron increases, the level of available iron decreases until eventually it is unable to meet cellular demands, which leads to a functional iron deficiency. Normally, the lysosome plays an integral role in cellular iron homeostasis by facilitating both the delivery of iron to the cytosol (e.g., after endocytosis of the iron–transferrin–transferrin receptor complex) and the cellular recycling of iron. During a lysosomal storage disorder, an enzyme deficiency causes undigested substrates to accumulate, causing a sequelae of pathogenic events that may include cellular iron dyshomeostasis. Thus, a functional deficiency of iron may be a pathogenic mechanism occurring within several lysosomal storage diseases and Alzheimer’s disease.

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Two siblings with Gaucher type 3c: different clinical presentations

Karakoyun

Canda

Taşçı

et al. 2019

Journal of Pediatric Endocrinology and Metabolism

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Background Gaucher disease (GD) is a lysosomal storage disorder caused by autosomal recessive mutations in the glucocerebrosidase (GBA) gene, which encodes acid β-glucosidase. GD type 3c is a rare group characterised by cardiovascular involvement, and homozygous D448H is the most frequent mutation. Case presentation We describe two patients who had homozygous D448H mutations. The index patient had hepatosplenomegaly, liver insufficiency and cardiac involvement and her sister had severe cardiac involvement with cardiomyopathy and diffuse aortic calcification. The index case’s liver was transplanted at the age of 6 months from a related donor and her sister who had severe cardiovascular disease died at the age of 12 years. Conclusions Our patients had clinical variability. We need to discuss whether liver involvement could be the initial signs in patients with GD type 3c.

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Clinical variability in neurohepatic syndrome due to combined mitochondrial DNA depletion and Gaucher disease

Cited by 3 publications

References 21 publications

A SUCLG1 mutation in a patient with mitochondrial DNA depletion and congenital anomalies

A SUCLG1 mutation in a patient with mitochondrial DNA depletion and congenital anomalies

Examining the Role of a Functional Deficiency of Iron in Lysosomal Storage Disorders with Translational Relevance to Alzheimer’s Disease

Two siblings with Gaucher type 3c: different clinical presentations

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