Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome

Li, Dongxiao; Song, Jinqing; Li, Xiyuan; Liu, Yi; Dong, Hui; Kang, Lulu; Liu, Yupeng; Zhang, Yao; Ying, Jianming; Guan, Hanzhou; Zhou, Chunmei; Yang, Yanling

doi:10.1016/j.ejmg.2020.104003

Cited by 10 publications

(20 citation statements)

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“…A total of 18 unrelated patients were included, including 11 females and 7 males, of whom 4 patients have been described previously ( Li et al, 2020 ). None of them had positive consanguinity.…”

Section: Resultsmentioning

confidence: 99%

“…Including our study, a total of 159 patients were diagnosed with THMD2 in 40 reports ( Ozand et al, 1998 ; Adhisivam et al, 2007 ; El-Hajj et al, 2008 ; Bindu et al, 2009 ; Kono et al, 2009 ; Debs et al, 2010 ; Yamada et al, 2010 ; Serrano et al, 2012 ; Alfadhel et al, 2013 ; Fassone et al, 2013 ; Gerards et al, 2013 ; Kevelam et al, 2013 ; Perez-Duenas et al, 2013 ; Tabarki et al, 2013a , b , 2015 ; Distelmaier et al, 2014 ; Haack et al, 2014 ; Kassem et al, 2014 ; Ortigoza-Escobar et al, 2014 , 2016 , 2017 ; Schanzer et al, 2014 ; Sremba et al, 2014 ; Kohrogi et al, 2015 ; Aljabri et al, 2016 ; Bin Saeedan and Dogar, 2016 ; Bubshait et al, 2016 ; Flones et al, 2016 ; Schwarting et al, 2016 ; Ygberg et al, 2016 ; Alfadhel, 2017 ; Algahtani et al, 2017 ; Eichler et al, 2017 ; Pronicki et al, 2017 ; Whitford et al, 2017 ; Gowda et al, 2018 ; Tonduti et al, 2018 ; Savasta et al, 2019 ; Li et al, 2020 ). Thirteen patients were excluded, including 9 patients without genetic results and 4 patients without clinical information.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 18 individuals with SLC19A3 mutations were recruited, of whom 4 cases had been reported previously ( Li et al, 2020 ). The study protocol was approved by the Ethic Committee of all hospitals involved.…”

Section: Methodsmentioning

confidence: 99%

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Report of the Largest Chinese Cohort With SLC19A3 Gene Defect and Literature Review

Wang

Han

et al. 2021

Front. Genet.

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Thiamine metabolism dysfunction syndrome 2 (THMD2) is a rare metabolic disorder caused by SLC19A3 mutations, inherited in autosomal recessive pattern. As a treatable disease, early diagnosis and therapy with vitamin supplementation is important to improve the prognosis. So far, the reported cases were mainly from Saudi Arab regions, and presented with relatively simple clinical course because of the hot spot mutation (T422A). Rare Chinese cases were described until now. In this study, we investigated 18 Chinese THMD2 patients with variable phenotypes, and identified 23 novel SLC19A3 mutations, which expanded the genetic and clinical spectrum of the disorder. Meanwhile, we reviewed all 146 reported patients from different countries. Approximately 2/3 of patients presented with classical BTBGD, while 1/3 of patients manifested as much earlier onset and poor prognosis, including infantile Leigh-like syndrome, infantile spasms, neonatal lactic acidosis and infantile BTBGD. Literature review showed that elevated lactate in blood and CSF, as well as abnormal OXPHOS activities of muscle or skin usually correlated with infantile phenotypes, which indicated poor outcome. Brainstem involvement on MRI was more common in deceased cases. Thiamine supplementation is indispensable in the treatment of THMD2, whereas combination of biotin and thiamine is not superior to thiamine alone. But biotin supplementation does work in some patients. Genotypic-phenotypic correlation remains unclear which needs further investigation, and biallelic truncated mutations usually led to more severe phenotype.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Report of the Largest Chinese Cohort With SLC19A3 Gene Defect and Literature Review

Wang

Han

et al. 2021

Front. Genet.

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“…This latter disease is characterized by an apparent congenital microcephaly, high levels of α-ketoglutarate in urine, brain malformations and psychomotor retardation with encephalopathy episodes [ 37 ]. Li et al identified the same variant c.454C>A p.(Pro152Thr) but not the same amino acid change, in a Chinese LS patient, as compound heterozygous together with another variation c.194C>T (p.Ala65Val) in the same gene [ 38 ]. Variants of SLC25A19 play a major role on the etiology of LS, since neurological LS symptoms are convergent toward a patho-mechanism of diseases related to thiamine transport.…”

Section: Discussionmentioning

confidence: 99%

Next-generation sequencing of Tunisian Leigh syndrome patients reveals novel variations: impact for diagnosis and treatment

et al. 2022

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Mitochondrial cytopathies, among which the Leigh syndrome (LS), are caused by variants either in the mitochondrial or the nuclear genome, affecting the oxidative phosphorylation process. The aim of this study consisted in defining the molecular diagnosis of a group of Tunisian patients with LS. Six children, belonging to five Tunisian families, with clinical and imaging presentations suggestive of LS were recruited. Whole mitochondrial DNA and targeted next generation sequencing of a panel of 281 nuclear genes involved in mitochondrial physiology were performed. Bioinformatic analyses were achieved in order to identify deleterious variations. A single m.10197G>A (p.Ala47Thr) variant was found in the mitochondrial MT-ND3 gene in one patient, while the others were related to autosomal homozygous variants: two c.1412delA (p.Gln471ArgfsTer42) and c.1264A>G (p.Thr422Ala) in SLC19A3, one c.454C>G (p.Pro152Ala) in SLC25A19 and one c.122G>A (p.Gly41Asp) in ETHE1. Our findings demonstrate the usefulness of genomic investigations to improve LS diagnosis in consanguineous populations, and further allow for treating the patients harboring variants in SLC19A3 and SLC25A19 that contribute to thiamine transport, by thiamine and biotin supplementation. Considering the Tunisian genetic background, the newly identified variants could be screened in patients with similar clinical presentation in related populations.

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“…Family history was notable because of the death of a sibling at 20 months, diagnosed to have Guillain-Barré syndrome, and a further sibling, with milder but similar symptoms with the index case. The episodic attacks of fever started at around 2 years of age and occurred every 2-3 years, triggered by respiratory tract infections (2, 4, and 10 years Table 1 Review of genetically identified patients diagnosed with thiamine metabolism dysfunction syndrome-4 in the literature (Iacobazzi et al, 2001;Spiegel et al, 2009;Ortigoza-Escobar et al, 2017;Bottega et al, 2019;Gowda et al, 2019;Li et al, 2020;Porta et al, 2021) of age). Each attack lasted for about 2 or 3 weeks, and he was given intravenous immunoglobulin (IVIG).…”

Section: Case Reportsmentioning

confidence: 99%

Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature

Samur

Gümüş

Canpolat

et al. 2022

Clinical Dysmorphology

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Thiamine metabolism dysfunction syndrome-4 (THMD-4) is an autosomal recessive inherited rare disease (OMIM #613710) characterized by febrile illness associated episodic encephalopathy, leading to transient neurological dysfunction and progressive polyneuropathy. We report three patients from two different families with normal development, episodic encephalopathy, gait disorder, progressive chronic polyneuropathy characterized by motor difficulties, distal weakness, and hoarseness (dysphonia). We identified a homozygous missense c.576G>C, p.(Gln192His) variant in the SLC25A19 gene in both families by whole-exome sequencing. Following genetic diagnosis, thiamine replacement therapy was started, and improvement was observed in all affected patients. We highlight the associated phenotypes of an SCL25A19 mutation leading to clinical features of THMD-4.

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Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome

Cited by 10 publications

References 23 publications

Report of the Largest Chinese Cohort With SLC19A3 Gene Defect and Literature Review

Report of the Largest Chinese Cohort With SLC19A3 Gene Defect and Literature Review

Next-generation sequencing of Tunisian Leigh syndrome patients reveals novel variations: impact for diagnosis and treatment

Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature

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