Diagnostic accuracy of blood and CSF lactate in identifying children with mitochondrial diseases affecting the central nervous system

Yamada, Keitaro; Toribe, Yasuhisa; Yanagihara, Keiko; Mano, Toshiyuki; Akagi, Mikihiro; Suzuki, Yasuhiro

doi:10.1016/j.braindev.2011.08.004

Cited by 37 publications

(28 citation statements)

References 14 publications

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“…The study population is a representative cohort of pediatric patients with clinically suspected MD at a tertiary hospital, making the study highly relevant to clinicians investigating these often severely sick children. The prevalence of MD in the study population was 16%, in line with previous reports from patient cohorts with similar clinical presentation (6,14,23).…”

Section: Discussionsupporting

confidence: 90%

“…Elevated blood lactate is an important indicator for MD, but is nonspecific and may be caused by numerous systemic conditions such as hypoxia or sepsis (5). Cerebrospinal fluid lactate is more specific in diagnosing mitochondrial encephalopathy, but requires an invasive procedure (6). Magnetic resonance imaging of the brain may show typical patterns (as in Leigh syndrome) or less specific pathology.…”

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confidence: 99%

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Oxygen consumption in platelets as an adjunct diagnostic method for pediatric mitochondrial disease

et al. 2017

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BackgroundDiagnosing mitochondrial disease (MD) is a challenge. In addition to genetic analyses, clinical practice is to perform invasive procedures such as muscle biopsy for biochemical and histochemical analyses. Blood cell respirometry is rapid and noninvasive. Our aim was to explore its possible role in diagnosing MD.MethodsBlood samples were collected from 113 pediatric patients, for whom MD was a differential diagnosis. A respiratory analysis model based on ratios (independent of mitochondrial specific content) was derived from a group of healthy controls and tested on the patients. The diagnostic accuracy of platelet respirometry was evaluated against routine diagnostic investigation.ResultsMD prevalence in the cohort was 16%. A ratio based on the respiratory response to adenosine diphosphate in the presence of complex I substrates had 96% specificity for disease and a positive likelihood ratio of 5.3. None of the individual ratios had sensitivity above 50%, but a combined model had 72% sensitivity.ConclusionNormal findings of platelet respirometry are not able to rule out MD, but pathological results make the diagnosis more likely and could strengthen the clinical decision to perform further invasive analyses. Our results encourage further study into the role of blood respirometry as an adjunct diagnostic tool for MD.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Oxygen consumption in platelets as an adjunct diagnostic method for pediatric mitochondrial disease

et al. 2017

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“…Nowadays, measurement of CSF lactate concentration is used as a reliable tool for the diagnosis of mitochondrial deficit, since elevated CSF lactate levels may represent the result of accumulating energetic metabolites due to mitochondrial dysfunction 23. In past years, high lactate concentrations were reported in CSF of patients with AD, thus supporting the hypothesis that mitochondria alteration may be involved in AD processes 10 11.…”

Section: Discussionmentioning

confidence: 97%

CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer's disease

Liguori

Stefani

Sancesario

et al. 2014

J Neurol Neurosurg Psychiatry

127

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We verified the occurrence of high CSF lactate levels in patients with AD, which may be ascribed to mitochondria impairment. Hypothesising that τ proteins may exert a detrimental effect on the entire cellular energy metabolism, the negative correlation found between lactate and τ-protein levels may allow speculation that τ toxicity, already demonstrated to have affected mitochondria, could also impair glycolytic metabolism with a less evident increase of lactate levels in more severe AD. Thus, we suggest a dynamic relationship between neuronal energy metabolism, τ proteins and cognitive decline in AD and propose the clinical potential of assessing CSF lactate levels in patients with AD to better define the neuronal brain metabolism damage.

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“…Not surprisingly, when excess NADH accumulates, lactate also accumulates and typically, high lactate is associated with hypoxia (Rimachi, et al 2012.) or other mitochondrial deficiencies (Yamada, et al 2012.). Lactate pyruvate ratio is a clinical surrogate for NAD + /NADH ratio in physiology.…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes

Cantó

Sauve

Bai

2013

Molecular Aspects of Medicine

219

188

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Poly(ADP-ribose) polymerases (PARPs) are NAD+ dependent enzymes that were identified as DNA repair proteins, however, today it seems clear that PARPs are responsible for a plethora of biological functions. Sirtuins (SIRTs) are NAD+-dependent deacetylase enzymes involved in the same biological processes as PARPs raising the question whether PARP and SIRT enzymes may interact with each other in physiological and pathophysiological conditions. Hereby we review the current understanding of the SIRT-PARP interplay in regard to the biochemical nature of the interaction (competition for the common NAD+ substrate, mutual posttranslational modifications and direct transcriptional effects) and the physiological, or pathophysiological consequences of the interactions (metabolic events, oxidative stress response, genomic stability and ageing). Finally, we give an overview of the possibilities of pharmacological intervention to modulate PARP and SIRT enzymes either directly, or through modulating NAD+ homeostasis.

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Diagnostic accuracy of blood and CSF lactate in identifying children with mitochondrial diseases affecting the central nervous system

Cited by 37 publications

References 14 publications

Oxygen consumption in platelets as an adjunct diagnostic method for pediatric mitochondrial disease

Oxygen consumption in platelets as an adjunct diagnostic method for pediatric mitochondrial disease

CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer's disease

Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes

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