Biotin-Thiamine Responsive Encephalopathy: Report of an Egyptian Family with a Novel SLC19A3 Mutation and Review of the Literature

Abstract

Biotin-thiamine responsive basal ganglia disease (BTRBGD) is an autosomal recessive neurometabolic disorder with poor genotype-phenotype correlation, caused by mutations in the SLC19A3 gene on chromosome 2q36.6. The disease is characterized by three stages: stage 1 is a sub-acute encephalopathy often triggered by febrile illness; stage 2 is an acute encephalopathy with seizures, loss of motor function, developmental regression, dystonia, external ophthalmoplegia, dysphagia, and dysarthria; stage 3 is represented by chronic or slowly progressive encephalopathy. Clinical and biochemical findings, as well as the magnetic resonance imaging (MRI) pattern, resemble those of Leigh's syndrome, so that BTRBGD can be misdiagnosed as a mitochondrial encephalopathy.Here we report the clinical and radiological phenotypes of two siblings diagnosed with BTRBGD in which a novel SLC19A3 mutation (NM_025243.3: c.548C > T; p.Ala183Val) was found by whole exome sequencing (WES) of the family members.

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

“…The clinical pictures in patients with infantile phenotypes were almost the same, all manifesting an acute devastating course during early months of life, with feeding difficulties, inconsolable crying or lethargy, loss of milestones. Respiratory failure and hypotonia were more common in patients of this group ( Yamada et al, 2010 ; Perez-Duenas et al, 2013 ; Gerards et al, 2013 ; Kevelam et al, 2013 ; Sremba et al, 2014 ; Ygberg et al, 2016 ; Alfadhel, 2017 ; Algahtani et al, 2017 ; Pronicki et al, 2017 ; Savasta et al, 2019 ). Wernicke’s-like encephalopathy was only described in two Japanese patients ( Kono et al, 2009 ).…”

“…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.…”

Biotin–Thiamine Responsive Basal Ganglia Disease Presented as Intractable Seizure in a 1-Month-Old Infant

“…It is a pan ethnic disease with most cases diagnosed in Saudi Arab. 2 Affected patients usually present in childhood, with average age of diagnosis 8 years; however, patients have been diagnosed as late as age 33 years. 3 Clinical characterization consists of three different stages with variable combinations of encephalopathy, seizures, coma, and death.…”

Are homozygous SLC19A3 deletions non-responsive to thiamine/biotin?

“…A fourth shortcoming is that no discussion was hold about the possibility that all the lesions seen on MRI were multi-locular stroke-like lesions (SLLs). 4 Since at least the supra-tentorial lesion were hyperintense on DWI and also the infra-tentorial lesions were described as DWI hyperintense, we should know if corresponding ADC maps were hyperintense, isointense, or hypointense. Knowing if a cytotoxic or vasogenic edema was present is crucial as therapy may be different from that applied in this case.…”

“…Such poor prognosis is especially common in patients with early neonatal Leighlike syndrome and the early infantile-onset form of BTBGD, as in our patient, even when treated with biotin and thiamine. 2,3 The fact that these patients show neurodevelopmental problems in various degrees despite early treatment 4,5 indicates that it may be too late to prevent permanent brain damage even when treatment is started at the time of the first symptoms. 6…”