Leigh's disease: significance of the biochemical changes in brain.

Murphy, Josephine; Craig, Linda

doi:10.1136/jnnp.38.11.1100

Cited by 5 publications

(4 citation statements)

References 13 publications

(10 reference statements)

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“…There are also two rare genetic conditions associated with thiamine deficiency. Leigh’s syndrome is due to a loss of the enzyme thiamine-diphosphate kinase, resulting in low thiamine triphosphate despite normal thiamine levels, and presents with failure to thrive, lactate acidosis, nystagmus, seizures and subacute necrotising encephalomyelopathy 18. There is also a variant of maple sugar urine disease that is thiamine sensitive and presents in childhood with development delay, learning disabilities, nausea, vomiting and lactic acidosis 19…”

Section: Causes Of Thiamine Deficiencymentioning

confidence: 99%

Thiamine deficiency: a commonly unrecognised but easily treatable condition

Schostak¹,

Millan

Jani³

et al. 2022

Postgraduate Medical Journal

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Thiamine is present in many foods and is well recognised as an essential nutrient critical for energy metabolism. While thiamine deficiency is commonly recognised in alcoholism, it can present in many other settings where it is often not considered and goes unrecognised. One challenging aspect to diagnosis is that it may have varied metabolic, neurological and cardiac presentations. Here we present an overview of the disorder, focusing on the multiple causes and clinical presentations. Interestingly, thiamine deficiency is likely increasing in frequency, especially among wildlife, where it is linked with changing environments and climate change. Thiamine deficiency should be considered whenever neurological or cardiological disease of unknown aetiology presents, especially in any patient presenting with lactic acidosis.

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Section: Causes Of Thiamine Deficiencymentioning

confidence: 99%

Thiamine deficiency: a commonly unrecognised but easily treatable condition

Schostak¹,

Millan

Jani³

et al. 2022

Postgraduate Medical Journal

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“…Though the function of TTP in the nervous system is not clear, the cited findings have suggested that TTP deficiency may be the underlying mechanism in the development of SNEM [l, [7][8][9][10][11]. Biochemical identification of the inhibitor factor in urine has been considered a diagnostic test for SNEM [7, lo].…”

mentioning

confidence: 99%

Leigh's disease in an adult with evidence of “inhibitor factor” in family members

Whetsell

Plaitakis

1978

Annals of Neurology

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A 21-year-old man with a longstanding history of impaired visual acuity, strabismus, broad-based gait, and below-average intellectual capacity developed respiratory difficulties and intermittent generalized weakness at age 19. He subsequently showed signs of massive brainstem dysfunction and died. Postmortem examination demonstrated changes compatible with subacute necrotizing encephalomyelopathy of Leigh involving portions of the diencephalon, midbrain, pons, and medulla as well as portions of the spinal cord and optic nerves. Evaluation of family members for presence of the urinary inhibitor factor for thiamine diphosphate phosphoryl transferase revealed abnormal levels in a brother, a maternal uncle, and the maternal grandfather of the patient.

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“…In addition to their well-known energy production function, mitochondria have other critical functions including calcium homeostasis (79,80), cell signaling, apoptosis (76) (81). Since mitochondria are inherited from maternal parents (76,77), mitochondrial dysfunction causing diabetes and deafness (82), Leigh's Disease (83), and NARP syndrome ( 84) are inherited through the oocyte.…”

Section: Mitochondriamentioning

confidence: 99%

“…It has been well documented that mitochondria are one of the important indicators of the oocyte quality and closely related to successful fertilization and embryonic developments (76). Since mitochondria contain genetic materials contributed from oocytes to the next generations, maternal mitochondrial dysfunction can cause various diseases in the resulting offspring including diabetes and deafness (82), Leigh's disease (83), and NARP syndrome (84).…”

Section: Introductionmentioning

confidence: 99%

Investigation of methods and factors influencing mouse oocyte quality, in vitro fertilization and embryo development

Wuri¹

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Mice are one of the most commonly used rodent species as a model for biomedical research to better understand molecular, genetic, and cellular causes of human disease and disorders. The production of good quality oocytes is one of the important determinant factors for successful assisted reproductive technologies (ARTs) clinical outcome as well as reproductive biology research. Mouse oocyte quality, morphology and functions are influenced by a variety of the factors such as euthanasia methods of female donors, superovulation regimes and cryopreservation. The objectives of these studies were mainly to investigate the methods and factors that are influencing oocyte quality, in-vitro fertilization (IVF) and embryonic development. First, how different euthanasia methods including cervical dislocation (CD), high flow rate CO[2] (H CO[2]) and low flow CO2 (L CO[2]) would affect the quality and integrity of the metaphase II (MII) oocytes have been investigated. Cumulus oocyte complexes (COCs) were collected from female donors that were euthanized by three different methods and then the oocytes' subcellular structures including microtubules, F-actin, cortical granules (CGs) and mitochondria integrities were detected by specific fluorescence dyes. The results showed that L CO[2] caused significant increase in the incidence of premature cortical granule exocytosis (PCGE) which might be responsible for significantly reducing the in-vitro fertilization (IVF) and embryonic development rate compared to CD and H CO[2]. Secondly, how the superovulation methods would affect the resulting oocyte morphology, quality, IVF competence and embryonic development was investigated. The anti-inhibin serum (AIS) superovulation method produced a significantly higher number of oocytes compared to the pregnant mare serum gonadotrophin (PMSG). Overall, both methods yielded oocytes with similar sizes and comparable subcellular structures including microtubules, F-actin, cortical granules and mitochondria. However, superovulation with AIS produced significantly thinner zona pellucide than PMSG and the perivitelline space of the oocytes generated from AIS were significantly larger than PMSG. There were no differences in terms of two-cell embryo development, or morula and blastocyst formation rates between AIS and PMSG when the oocytes from two methods were in-vitro fertilized with fresh sperm. Morula and blastocyst development rates were significantly higher for AIS compared to PMSG when oocytes were fertilized with frozen-thawed sperm. Thirdly, clutches of mouse cumulus oocytes complexes (COCs) were cryopreserved by the cryoloop vitrification method after PMSG superovulation. The cryo-survival rate and integrity and distribution of subcellular structures including the meiotic spindles, F-actin, cortical granules and mitochondria were examined and compared with fresh MII oocytes. The vitrified-warmed oocytes maintained their subcellular structures to a high degree and resulted in acceptable IVF and embryonic development. In conclusion, for optimal research and clinical outcome, considerations should be given regard to euthanasia methods of oocyte donor mice and type of superovulation regimes. Despite of its high oocyte yield, superovulation of mice with AIS provides comparable quality oocytes to the PMSG method. Cryopreservation of the clutches of mouse COCs via cryo-loop vitrification should be considered for genome banking of genetically modified mice and biomedical research.

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Leigh's disease: significance of the biochemical changes in brain.

Cited by 5 publications

References 13 publications

Thiamine deficiency: a commonly unrecognised but easily treatable condition

Thiamine deficiency: a commonly unrecognised but easily treatable condition

Leigh's disease in an adult with evidence of “inhibitor factor” in family members

Investigation of methods and factors influencing mouse oocyte quality, in vitro fertilization and embryo development

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