A patient with congenital hyperlactataemia and Leigh syndrome: an uncommon mitochondrial variant

Ching, Chor Kwan; Mak, Chloe Miu; Au, K M; Chan, Kirsten; Yuen, Yuet-Ping; Yau, Eric; Louis, Christos; Chow, Hung; Chan, Andrew

doi:10.12809/hkmj133673

Cited by 6 publications

(4 citation statements)

References 12 publications

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“…The m.13094T>C mutation, in the MT-ND5 gene, is considered a rare pathogenic variant that has been previously reported in association with LS but the full phenotypic spectrum has remained poorly understood ( Valente et al, 2009 ; Ching et al, 2013 ). We present the clinical, radiological, and histopathological data of 24 subjects who harbor the m.13094T>C mutation.…”

Section: Introductionmentioning

confidence: 99%

MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load

Lax

Maddison

et al. 2018

eBioMedicine

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Mutations in the m.13094T>C MT-ND5 gene have been previously described in three cases of Leigh Syndrome (LS). In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families) and four asymptomatic carriers. Ten patients were deceased at the time of analysis (median age of death was 10 years (range: 5·4 months−37 years, IQR = 17·9 years). Nine patients manifested with LS, one with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and one with Leber hereditary optic neuropathy. The remaining nine patients presented with either overlapping syndromes or isolated neurological symptoms. Mitochondrial respiratory chain activity analysis was normal in five out of ten muscle biopsies. We confirmed maternal inheritance in six families, and demonstrated marked variability in tissue segregation, and phenotypic expression at relatively low blood mutant loads. Neuropathological studies of two patients manifesting with LS/MELAS showed prominent capillary proliferation, microvacuolation and severe neuronal cell loss in the brainstem and cerebellum, with conspicuous absence of basal ganglia involvement. These findings suggest that whole mtDNA genome sequencing should be considered in patients with suspected mitochondrial disease presenting with complex neurological manifestations, which would identify over 300 known pathogenic variants including the m.13094T>C.

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Section: Introductionmentioning

confidence: 99%

MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load

Lax

Maddison

et al. 2018

eBioMedicine

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“…In addition to plant sterol dietary restriction, the pharmacotherapy with ezetimibe can lead to the reduction of blood phytosterol concentrations [1]. It is interesting to note that unlike familial hypercholesterinemia in sitosterolemia, xanthomas could disappear [27,28].…”

Section: Discussionmentioning

confidence: 99%

Pediatric Patients with Sitosterolemia: Next-Generation Sequencing and Biochemical Examination in Clinical Practice

Miroshnikova,

Vasiluev,

Linkova

et al. 2023

JPM

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Here, we report the pediatric cases of sitosterolemia, a rare autosomal-recessive genetic disorder, characterized by high concentrations of plant sterols in blood and heterogeneity manifestations. All three patients (two girls aged 2 and 6 years old, and one boy aged 14 years old) were initially diagnosed with hypercholesterinemia. Next-generation sequencing (NGS) revealed homozygous (p.Leu572Pro/p.Leu572Pro) and compound (p.Leu572Pro/p.Gly512Arg and p.Leu572Pro/p.Trp361*) variants in the ABCG8 gene that allowed for the diagnosis of sitosterolemia. Two patients whose blood phytosterol levels were estimated before the diet demonstrated high levels of sitosterol/campesterol (69.6/29.2 and 28.3/12.4 μmol/L, respectively). Here, we demonstrate that NGS-testing led to the proper diagnosis that is essential for patients’ management. The variant p.Leu572Pro might be prevalent among patients with sitosterolemia in Russia.

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“…A total of 119 patients had con rmed MD either by molecular diagnosis and/or enzymatic analysis, including some cases that have been published in the literature. [13][14][15][16][17][18][19][20][21][22][23] The patients' demographics are summarized in Table 1. Molecular diagnosis was available for 110 patients (92%).…”

Section: Demographics and Epidemiologymentioning

confidence: 99%

Mitochondrial Diseases in Hong Kong: Prevalence, Clinical characteristics and Genetic landscape

Wong

Belaramani

Chan

et al. 2022

Preprint

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Objective: To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region. Methods: This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators. Results: A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81 – 1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%. Conclusion: This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry.

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A patient with congenital hyperlactataemia and Leigh syndrome: an uncommon mitochondrial variant

Cited by 6 publications

References 12 publications

MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load

MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load

Pediatric Patients with Sitosterolemia: Next-Generation Sequencing and Biochemical Examination in Clinical Practice

Mitochondrial Diseases in Hong Kong: Prevalence, Clinical characteristics and Genetic landscape

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