Background
Biotin thiamine responsive basal ganglia disease (BTRBGD) is an inherited autosomal recessive disorder that results from the inability of thiamine to cross the blood–brain barrier. It is considered a treatable condition if vitamin supplementation, most commonly with thiamine and biotin, is initiated early. BTRBGD can present as an infantile form, classical childhood form, or adult Wernicke-like encephalopathy. The infantile form is often the most severe and presents a worse prognosis with high mortality despite vitamin supplementation.
Case Presentation
A 2-month-old, ex-full term, developmentally appropriate girl presented to the hospital with abnormal eye movements described as a transient forced downward gaze and exaggerated eyelid opening.
Physical Examination
Her fontanelle was soft, and her neurologic examination was normal except for intermittent exaggerated eye opening.
Medical History
- Two days before presentation, the patient developed projectile vomiting with feeding.
- She remained afebrile but seemed fussier than usual.
- Her parents described paroxysmal tonic downgaze of her eyes.
- She was admitted for evaluation of possible seizures, infantile spasms, or increased intracranial pressure, among other possible causes for new-onset irritability and abnormal eye movements.
Clinical Evaluation
Figure. MRI and MR Spectroscopy Findings in BTRBGD. Adapted from source
Treatment
- The pattern of injury was suspicious for a metabolic or mitochondrial disorder, in particular Leigh syndrome or biotin-thiamine-responsive basal ganglia disease (BTRBGD); therefore, she was empirically started on high dose biotin (10 mg/kg daily) and thiamine (20 mg/kg daily) immediately.
- A GeneDx MitoXpanded panel was sent, which was positive for 2 variants in the SLC19A3 gene, assumed to be inherited in trans.
- An analysis showed that the pathogenic variant (c.1314+1, G>A) was present in the patient’s mother, whereas the variant of uncertain significance (c.298 G>C) was not present in either parent, suggesting that the patient’s mother was a carrier of one variant, and our patient had a de novo mutation in the opposite allele that resulted in disease.
- The patient’s spells and irritability resolved within 1–2 days of supplementation. Because she had regressed in motor and social behavior at onset, physical therapy was started upon discharge.
Follow up
At the follow-up at 7 months of age, she was noted to have axial hypotonia, mild gross motor delay, and intermittent right esotropia only, demonstrating improvement in her development after supplementation.