ABSTRACT
BACKGROUND: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare, autosomal recessive neurometabolic disorder caused by mutations in the SLC19A3 gene and characterized by recurrent sub-acute episodes of encephalopathy. Patients with BTBGD have classical neuroimaging findings and a dramatic response to high doses of thiamine. OBJECTIVE: To highlight the advantages of administering a higher dose of thiamine for patients with BTBGD who have not shown improvement with the standard recommended dosage. RESULTS: Herein, we report on two Saudi girls with classical clinical and radiological findings of BTBGD. Hallmark symptoms in these patients included an acute onset of ataxia, tremor, slurred speech, dystonia, and dysphagia. The initial routine laboratory workups were unremarkable. Brain magnetic resonance imaging revealed extensive hyperintense signals in the bilateral basal ganglia, which suggested the diagnosis of a BTBGD. Hence started empirically on biotin 10 mg/kg/day and thiamine 40 mg/kg/day, but there was no noticeable improvement. After increasing the thiamine to 75 mg/kg/day the patients started to improve significantly. Genetic testing was requested and came positive for the mutation of the SLC19A3 gene. After two months of initiating the management, thiamine was reduced to 30 mg/kg/day. Subsequent follow-ups showed complete improvement in their condition with no apparent long-term sequel or relapse. CONCLUSION: we conclude that administration of thiamine at a dosage of up to 40 mg/kg/day may not be sufficient in treating certain patients with BTBGD. Thus, considering a significantly higher dosage could potentially contribute to achieving remission.
ABSTRACT
Background and Purpose: To determine the common precipitating factors for breakthrough seizures in children with epilepsy. Methods: This retrospective study reviewed the charts of children with epilepsy who were followed up in the pediatric neurology clinic of King Fahad Hospital in Al-Baha region, Saudi Arabia, between January 2015 and August 2022. Children between 1 to 14 years of age who had epilepsy, as per the International League Against Epilepsy definition and received anti-seizure medication with a seizure-free period of at least 2 months before breakthrough seizure episode, were included in the study. Results: Of the 108 children included in the study, the mean age was 6.8±1.6 years, and among them (55.5%) were male. Most parents (69.5%) were unaware of the triggering factors of seizure. The majority of patients (88%) reported at least one precipitating factor for breakthrough seizures and the most common one was systemic infection associated with fever (52.8%), and then non-compliance to medications in (34.3%) of the patients. In terms of the electroencephalogram, around 84 patients (77.8%) had abnormal electroencephalogram. Finally, monotherapy was maintained in 63.9% of patients. Conclusions: We conclude that the most common trigger for breakthrough seizure is a systemic infection associated with fever and non-compliance to anti-seizure medications. Increasing the level of awareness by different methods may help limit or even prevent seizures from occurring. Randomized controlled trials could shed light on the adjustment of anti-seizure medications temporarily by increasing the dosage or giving extra doses during the infection to avoid breakthrough seizures.
ABSTRACT
Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare, inherited neurometabolic disorder caused by mutations in the SLC19A3 gene and characterized by recurrent sub-acute episodes of encephalopathy that are often triggered by infections. Patients with BTBGD have classical neuroimaging findings and a dramatic response to high doses of thiamine. Herein, we report a 2 and a half-year-old Saudi girl presented with an acute onset of ataxia, slurred speech, and dysphagia, which was preceded by a history of accidental ingestion of around 20 mL of ethyl alcohol that is used in formulating perfumes 1 day earlier. Her older brother had a similar clinical presentation and was diagnosed with BTBGD. The patient was fully alert and spoke in full sentences with dysarthria. She was unable to walk unassisted. Investigation revealed a positive toxicity test for ethyl alcohol (10 mg/dL), and brain magnetic resonance imaging showed basal ganglia changes consistent with BTBGD. The dramatic response to high doses of thiamine suggested SLC19A3 as a strong candidate gene, and Sanger sequencing revealed a homozygous (NM_025243.4): c.1264A>G (p.Thr422Ala) mutation. Patients with BTBGD should be cautious and aware of ethyl alcohol products, which can lead to a BTBGD crisis. The administration of a high dose of thiamin may be required in patients who have not responded to the recommended dose. Further clinical research is required to determine the optimal doses.
