We evaluated coenzyme Q 10 (CoQ) levels in patients studied under suspicion of mitochondrial DNA depletion syndromes (MDS) (n=39). CoQ levels were quantified by HPLC, and the percentage of mtDNA depletion by quantitative real-time PCR. A high percentage of MDS patients presented with CoQ deficiency as compared to other mitochondrial patients (Mann-Whitney-U test: p= 0.001). Our findings suggest that MDS are frequently associated with CoQ deficiency, as a possible secondary consequence of disease pathophysiology. Assessment of muscle CoQ status seems advisable in MDS patients since the possibility of CoQ supplementation may then be considered as a candidate therapy.
KeywordsMitochondrial DNA depletion syndrome; coenzyme Q 10 deficiency; mitochondrial disorders.
AbbreviationsCoenzyme Q 10 (CoQ); mitochondrial DNA depletion syndromes (MDS); high pressure liquid chromatography (HPLC); mitochondrial DNA (mtDNA); mitochondrial respiratory chain (MRC); citrate synthase (CS);
Mitochondrial respiratory chain diseases are a heterogeneous group of pathologies caused by genetic alterations affecting mitochondrial energy production. Theoretically, this deficiency may lead to any symptoms, in any organ or tissue, at any age even before birth. The aim of our study was to identify the frequency and characterize antenatal manifestations identifying possible associations between mitochondrial disease and more specific and earlier manifestation. We retrospectively review the files of 44 paediatric subjects with genetic and biochemical alterations of respiratory chain identified in the first decade of life and compare data with a control group (n = 88). Our results show that maternal age was similar in both groups. The female gender was predominant in patients group. Gestational age at delivery was similar in both groups. Concerning birth weight, it was significantly lower (p = 0.001) in patients (2899.9 ± 538.3 vs. 3246.6 ± 460.2 g). Fifteen pregnancies of the patients group were considered abnormal. Our findings show that intrauterine growth restriction was the most frequent antenatal feature observed. Neonatal morbidity was significantly higher (fivefold) in patients (p < 0.001). The clinical findings are independent of the molecular defect type. Our results are preliminary and more studies are needed, in order to learn more about mitochondrial physiology and activity in embryological development for the assessment of mitochondrial disease progress in fetal life. However, the present work is a significant contribution, given the scarcity of information in this field.
Frontotemporal dementia (FTD) is the second most common type of primary degenerative dementia. Some patients present an overlap between Alzheimer's disease (AD) and FTD both in neuropathological and clinical aspects. This may suggest a similar overlap in physiopathology, namely an involvement of mitochondrial DNA (mtDNA) in FTD, as it has been associated to AD. To determine if mtDNA is involved in FTD, we performed a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis, specific to mtDNA NADH Dehydrogenase subunit 1 (ND1) nucleotides 3337-3340, searching for mutations previously described in Parkinson's and AD patients. We could identify one FTD patient with two mtDNA transitions: one already known (3316 G-to-A) and another unreported (3337 G-to-A). Additionally, mitochondrial respiratory chain complex I activity was reduced in leukocytes of this patient (36% of the control mean activity). To our knowledge, this is the first report of mtDNA variants in FTD patients.
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