Treatment of biotin-responsive basal ganglia disease: Open comparative study between the combination of biotin plus thiamine versus thiamine alone

Tabarki, Brahim; Alfadhel, Majid; AlShahwan, Saad; Hundallah, Khaled; Al-Shafi, Shatha; Alhashem, Amal

doi:10.1016/j.ejpn.2015.05.008

Cited by 49 publications

(41 citation statements)

References 10 publications

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“…Mice were housed in groups of 2–5 per cage and were identified by ear notches. Since there are both male and female patients with TMHD2 [17, 25], we analyzed both male and female mice in this study.…”

Section: Methodsmentioning

confidence: 99%

High-dose thiamine prevents brain lesions and prolongs survival of Slc19a3-deficient mice

et al. 2017

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SLC19A3 deficiency, also called thiamine metabolism dysfunction syndrome-2 (THMD2; OMIM 607483), is an autosomal recessive neurodegenerative disorder caused by mutations in SLC19A3, the gene encoding thiamine transporter 2. To investigate the molecular mechanisms of neurodegeneration in SLC19A3 deficiency and whether administration of high-dose thiamine prevents neurodegeneration, we generated homozygous Slc19a3 E314Q knock-in (KI) mice harboring the mutation corresponding to the human SLC19A3 E320Q, which is associated with the severe form of THMD2. Homozygous KI mice and previously reported homozygous Slc19a3 knock-out (KO) mice fed a thiamine-restricted diet (thiamine: 0.60 mg/100 g food) died within 30 and 12 days, respectively, with dramatically decreased thiamine concentration in the blood and brain, acute neurodegeneration, and astrogliosis in the submedial nucleus of the thalamus and ventral anterior-lateral complex of the thalamus. These findings may bear some features of thiamine-deficient mice generated by pyrithiamine injection and a thiamine-deficient diet, suggesting that the primary cause of THMD2 could be thiamine pyrophosphate (TPP) deficiency. Next, we analyzed the therapeutic effects of high-dose thiamine treatment. When the diet was reverted to a conventional diet (thiamine: 1.71 mg/100 g food) after thiamine restriction, all homozygous KO mice died. In contrast, when the diet was changed to a high-thiamine diet (thiamine: 8.50 mg/100 g food) after thiamine restriction, more than half of homozygous KO mice survived, without progression of brain lesions. Unexpectedly, when the high-thiamine diet of recovered mice was reverted to a conventional diet, some homozygous KO mice died. These results showed that acute neurodegeneration caused by thiamine deficiency is preventable in most parts, and prompt high-dose thiamine administration is critical for the treatment of THMD2. However, reduction of thiamine should be performed carefully to prevent recurrence after recovery of the disease.

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Section: Methodsmentioning

confidence: 99%

High-dose thiamine prevents brain lesions and prolongs survival of Slc19a3-deficient mice

et al. 2017

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“…The disease is characterized by early onset encephalopathy (usually below the age of 4 years). In many case reports, febrile illness preceded the manifestation disease; this febrile illness progresses to severe disability, dystonia, ataxia, seizures, and death if the patients were not treated with biotin and thiamine supplements [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Reliability of MRI in detection and differentiation of acute neonatal/pediatric encephalopathy causes among neonatal/pediatric intensive care unit patients

Hassan

Mohey

2020

Egypt J Radiol Nucl Med

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Background: Causes of encephalopathy in neonates/pediatrics include hypoxic-ischemic injury (which is the most frequent cause and is defined as any impairment to the brain caused by insufficient blood flow and oxygenation), trauma, metabolic disorders, and congenital and infectious diseases. The aim of this study is to evaluate the value of MRI in detection and possible differentiation of different non-traumatic, non-infectious causes of acute neonatal/ pediatric encephalopathy among NICU/PICU patients. Results: This retrospective study included 60 selected patients according to the study inclusion and exclusion criteria; all presented with positive MRI findings for non-traumatic, non-infectious acute brain injury. Females (32, 53.3%) were affected more than males (28, 46.7%) with a mean age of 1.1 ± 1.02 years; all presented with variable neurological symptoms and signs that necessitate neonatal intensive care unit/pediatric intensive care unit (NICU/ PICU) admission. The final diagnosis of the study group patients were hypoxic ischemia injury (HII) in 39 patients (65%), metachromatic leukodystrophy in 6 patients (10%), biotin-thiamine-responsive basal ganglia disease (BTBGD) and Leigh disease each in 4 patients (6.7%), periventricular leukomalacia (PVL) in 3 patients (5%), and mitochondrial encephalopathy with lactic acidosis and stroke-like episodes syndrome (MELAS) and non-ketotic hyperglycinemia (NKH) each in 2 patients (3.3%). Conclusion: Much attention should be paid to pediatric non-traumatic brain injuries. MRI is a safe modality and should be the first radiological investigation if neurological causes are suggested but should be aided by meticulous clinical evaluation and dedicated laboratory investigations for better characterization and differentiation of various causes of non-traumatic, non-infective brain encephalopathy among NICU/PICU patients. When interpreting MRI, it is essential to have thorough relevant clinical data, gestational age at birth which is prognostic of the pattern of hypoxic-ischemic injury, and the time lag between the onset of HII and the time of performing the MR study.

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“…It is thus intriguing that the disease was initially described as being responsive to biotin (Ozand et al, ), but this is likely related to the fact that biotin increases the expression of SLC19A3 , and individuals with biotin deficiency will only show 33% gene expression as compared to controls, ranging from 16 to 70% (Vlasova, Stratton, Wells, Mock, & Mock, ). However, a recent open‐label, prospective, comparative study showed that the combination of thiamine plus biotin was not superior to thiamine alone in terms of number of recurrences, neurologic sequelae or brain MRI findings, but it was associated with decreased duration of the acute crises (Tabarki et al, ). Indeed, it is known that normal cells exhibit upregulation of SLC19A3 expression under situations of stress, but this adaptive stress‐induced upregulation of gene expression is lost in patients with BTBGD (Schänzer et al, ).…”

Section: Discussionmentioning

confidence: 99%

Biotin‐thiamine responsive basal ganglia disease: Identification of a pyruvate peak on brain spectroscopy, novel mutation in SLC19A3, and calculation of prevalence based on allele frequencies from aggregated next‐generation sequencing data

Ferreira

Whitehead

Leon

2017

American J of Med Genetics Pt A

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Biotin-thiamine responsive basal ganglia disease is an inborn error of metabolism caused by mutations in SLC19A3, encoding a transporter of thiamine across the plasma membrane. We report a novel mutation identified in the homozygous state in a patient with typical brain MRI changes. In addition, this patient had markedly elevated CSF pyruvate, a low lactate-to-pyruvate molar ratio, and an abnormal pyruvate peak at 2.4 ppm on brain magnetic resonance spectroscopy. Using aggregated exome sequencing data, we calculate the carrier frequency of mutations in SLC19A3 as 1 in 232 individuals in the general population, for an estimated prevalence of the disease of approximately 1 in 215,000 individuals. The disease is thus more frequent than previously recognized, and the presence of a pyruvate peak on spectroscopy could serve as an important diagnostic clue.

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Treatment of biotin-responsive basal ganglia disease: Open comparative study between the combination of biotin plus thiamine versus thiamine alone

Cited by 49 publications

References 10 publications

High-dose thiamine prevents brain lesions and prolongs survival of Slc19a3-deficient mice

High-dose thiamine prevents brain lesions and prolongs survival of Slc19a3-deficient mice

Reliability of MRI in detection and differentiation of acute neonatal/pediatric encephalopathy causes among neonatal/pediatric intensive care unit patients

Biotin‐thiamine responsive basal ganglia disease: Identification of a pyruvate peak on brain spectroscopy, novel mutation in SLC19A3, and calculation of prevalence based on allele frequencies from aggregated next‐generation sequencing data

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