SLC19A3 Gene Defects Sorting the Phenotype and Acronyms: Review

Alfadhel, Majid; Tabarki, Brahim

doi:10.1055/s-0037-1607191

Cited by 31 publications

(9 citation statements)

References 42 publications

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“…The diagnosis of a thiamine transporter-2 deficiency was provided by the finding of the c.74 dup mutation in the SLC19A3 gene. This mutation has been reported in association with a clinical phenotype of early infantile Leigh-like encephalopathy/Atypical infantile spasms characterized by an acute devastating course during the first and third months of life with little chance of improvement under biotin and thiamine regimens ( Alfadhel, 2017;Alfadhel and Tabarki, 2018 ). The L patient's auditory evoked potentials were recorded when he was 1.5 month.…”

Section: Case Reportmentioning

confidence: 98%

Subcortical neural generators of the envelope-following response in sleeping children: A transfer function analysis

Lucchetti

Nonclercq

Avan³

et al. 2021

Hearing Research

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Multiple auditory structures, from cochlea to cortex, phase-lock to the envelope of complex stimuli. The relative contributions of these structures to the human surface-recorded envelope-following response (EFR) are still uncertain. Identification of the active contributor(s) is complicated by the fact that even the simplest two-tone ( f 1 & f 2 ) stimulus, targeting its ( f 2 − f 1 ) envelope, evokes additional linear ( f 1 & f 2 ) and non-linear ( 2 f 1 − f 2 ) phase-locked components as well as a transient auditory brainstem response (ABR). Here, we took advantage of the generalized primary tone phase variation method to isolate each predictable component in the time domain, allowing direct measurements of onset latency, duration and phase discontinuity values from which the involved generators were inferred. Targeting several envelope frequencies (0.22-1 kHz), we derived the EFR transfer functions along a vertical vertex-to-neck and a horizontal earlobe-to-earlobe recording channels, yielding respectively EFR-V and EFR-H waveforms. Subjects ( N = 30) were sleeping children with normal electrophysiological thresholds and normal oto-acoustic emissions. Both EFR-H and EFR-V phase-locking values (PLV) transfer functions had a low-pass profile, EFR-V showing a lower cut-off frequency than EFR-H. We also computed the frequency-latency relationships of both EFRs onset latencies. EFR-H data fitted a power-law function incorporating a frequencydependent traveling wave delay and a fixed one amounting to 1.2 ms. The fitted function nicely fell within five published estimations of the latency-frequency function of the ABR wave-I, thus pointing to a cochlear nerve origin. The absence of phase discontinuity and overall response durations that were equal to that of the stimulus indicated no contribution from a later generator. The recording of an entirely similar EFR-H response in a patient who had severe brainstem encephalitis with a normal, isolated, ABR wave-I but complete absence of later waves, further substantiated a cochlear nerve origin. Modeling of the EFR-V latency-frequency functions indicated a fixed transport time of 2 ms with respect to EFR-H onset, suggesting a cochlear nucleus (CN) origin, here also, without indication for multiple generators. Other features of the EFR-V response pointing to the CN were, at least for the EFR frequency below the cut-off values of the transfer functions, higher PLVs coupled with increased harmonic distortion. Such a behavior has been described in the so-called highly-synchronized neurons of the ventral cochlear nucleus (VCN). The present study compellingly demonstrated the advantage of isolating the EFR in the temporal domain so as to extract detailed spectro-temporal parameters that, combined with orthogonal recording channels, shed new light on the involved neural generators.

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Section: Case Reportmentioning

confidence: 98%

Subcortical neural generators of the envelope-following response in sleeping children: A transfer function analysis

Lucchetti

Nonclercq

Avan³

et al. 2021

Hearing Research

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“…Mutations in black box were found in Wernicke's-like encephalopathy. (Alfadhel and Tabarki, 2018). Through review of the literature, patients of classical form accounted for 69.2%.…”

Section: Discussionmentioning

confidence: 99%

“…SLC19A3 gene deficiency is associated with a continuum of clinical syndrome with variable outcomes ( Alfadhel and Tabarki, 2018 ). Through review of the literature, patients of classical form accounted for 69.2%.…”

Section: Discussionmentioning

confidence: 99%

“…The protein is formed by 12 transmembrane domains flanked by cytoplasmic N- and C- terminal regions ( Ganapathy et al, 2004 ). So far, over a hundred patients have been reported, mainly from Saudi Arab regions ( Alfadhel and Tabarki, 2018 ), whereas rare Chinese cases were reported. In this study, we described the largest cohort of Chinese population with SLC19A3 gene defect and reviewed all reported cases to elucidated its phenotypic and genetic spectrum.…”

Section: Introductionmentioning

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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“…The clinical presentations of these syndromes are heterogeneous and related to the age of onset. They can be classified into three major categories: classical childhood BBGD, early-infantile Leigh-like syndrome/atypical infantile spasms and adult Wernicke's-like encephalopathy [20]. Episodes of encephalopathy are caused by a substantially reduced capacity of mutant neuronal cells to increase SLC19A3 expression, necessary to adapt to stress conditions [21].…”

Section: Introductionmentioning

confidence: 99%

The Relevance of Thiamine Evaluation in a Practical Setting

Pacei

Tesone²,

Laudi

et al. 2020

Nutrients

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Thiamine is a crucial cofactor involved in the maintenance of carbohydrate metabolism and participates in multiple cellular metabolic processes. Although thiamine can be obtained from various food sources, some common food groups are deficient in thiamine, and it can be denatured by high temperature and pH. Additionally, different drugs can alter thiamine metabolism. In addition, the half-life of thiamine in the body is between 1 and 3 weeks. All these factors could provide an explanation for the relatively short period needed to develop thiamine deficiency and observe the consequent clinical symptoms. Thiamine deficiency could lead to neurological and cardiological problems. These clinical conditions could be severe or even fatal. Marginal deficiency too may promote weaker symptoms that might be overlooked. Patients undergoing upper gastrointestinal or pancreatic surgery could have or develop thiamine deficiency for many different reasons. To achieve the best outcome for these patients, we strongly recommend the execution of both an adequate preoperative nutritional assessment, which includes thiamine evaluation, and a close nutritional follow up to avoid a nutrient deficit in the postoperative period.

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SLC19A3 Gene Defects Sorting the Phenotype and Acronyms: Review

Cited by 31 publications

References 42 publications

Subcortical neural generators of the envelope-following response in sleeping children: A transfer function analysis

Subcortical neural generators of the envelope-following response in sleeping children: A transfer function analysis

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

The Relevance of Thiamine Evaluation in a Practical Setting

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