Biotin-thiamine-responsive basal ganglia disease

Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare neurometabolic syndrome caused by defective thiamine transporter 2 (THTR2) activity due to mutations in the solute carrier family 19 member 3 gene (SLC19A3). 

The presentation of BTBGD is variable and has been documented to occur at any point from birth to early adulthood. Symptom onset is most often between 3 and 10 years of age. 

Children affected by BTBGD typically present with intermittent subacute encephalopathy. Movement disorder, cognitive deficits, and seizures are classical. In addition, palsies affecting nerves to the head and neck cause deficits in facial expression, eye movement, mastication and swallowing. Interestingly, acute episodes of encephalopathy often follow a febrile illness or significant stress. 

Left untreated, BTBGD may progress to severe incapacitation, coma, and death.

In some cases, BTBGD presents insidiously with slowly progressive, chronic dystonia, seizures, and developmental delay 1

Thiamine is vital for energy metabolism in the brain, with thiamine deficiency causing a multitude of neurological deficits. Specifically, in addition to BTBGD, there are five disease phenotypes associated with variants in SLC19A3

  • Wernicke-like encephalopathy
  • infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome
  • Leigh syndrome with leukodystrophy
  • thiamine metabolism dysfunction syndrome 2
  • thiamine-responsive encephalopathy

In humans, there is no biological pathway for thiamine synthesis and so normal cellular function is almost exclusively dependent on uptake by thiamine transporter 1 (THTR1) and THTR2. 

MRI of an acute episode demonstrates severe vasogenic edema. Atrophy, necrosis and gliosis are observed at follow-up. These findings have been described in all reported cases of BTBGD 2. Abnormal signal intensity signifying loss or impairment of nervous tissue is classically observed within the head of the caudate with complete or partial involvement of the putamen. Lesions may also be observed diffusely throughout the cortex. The thalami, brainstem, cerebellum, and spinal cord are less frequently affected.

Treatment with high-dose biotin and thiamine supplementation early in disease progression rapidly evokes a complete, or at least partial, response in many patients. 

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Article information

rID: 65036
Tag: cases, refs
Synonyms or Alternate Spellings:
  • Biotin-thiamine-responsive basal ganglia disease (BTBGD)

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