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Biotin-Thiamine-Responsive Basal Ganglia Disease.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2013 Nov 21.

Author information

1
Prince Sultan Military and Medical City, Riyadh, Saudi Arabia
2
King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

Excerpt

CLINICAL CHARACTERISTICS:

Biotin-thiamine-responsive basal ganglia disease (BTBGD) is characterized by recurrent subacute encephalopathy manifest as confusion, seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and/or dysphagia which, if left untreated, can eventually lead to coma and even death. Dystonia and cogwheel rigidity are nearly always present; hyperreflexia, ankle clonus, and Babinski responses are common. Hemiparesis or quadriparesis may be seen. Episodes are often triggered by febrile illness or mild trauma or surgery. Less frequently, BTBGD presents as chronic or slowly progressive dystonia, seizures, and/or psychomotor delay. Although onset is usually in childhood (ages three to ten 10 years), it is extremely variable, ranging from the newborn period to adulthood. Prompt administration of biotin and thiamine early in the disease course results in partial or complete improvement within days.

DIAGNOSIS/TESTING:

Brain MRI shows symmetric and bilateral increased T2 signal intensity in the central part of caudate head and part or all of the putamen, as well as involvement of the globi pallidi, thalami, infra-and supratentorial brain cortex, brain stem, and cerebellum. During acute crises, severe vasogenic edema can be observed; chronic changes include atrophy, necrosis, and gliosis in the affected regions. The diagnosis of BTBGD is confirmed by identification of biallelic SLC19A3 pathogenic variants.

MANAGEMENT:

Treatment of manifestations: Biotin (5-10 mg/kg/day) and thiamine (in doses ranging from 300 to 900 mg) are given orally as early in the disease course as possible and are continued lifelong. Symptoms typically resolve within days. Acute encephalopathic episodes may require care in an ICU to manage seizures and increased intracranial pressure; during acute decompensations thiamine may be increased to double the regular dose and be given intravenously. Treatment of dystonia is symptomatic and includes administration of L-dopa. Rehabilitation, physiotherapy, occupational therapy, and speech therapy as needed. Adaptation of educational programs to meet individual needs. Prevention of primary manifestations: Prompt administration of biotin and thiamine early in the disease course. Surveillance: Evaluation every six months by the treating subspecialists. Agents/circumstances to avoid: Stress, trauma. Evaluation of relatives at risk: If the pathogenic variants have been identified in an affected family member, perform molecular genetic testing on at-risk relatives (e.g., sibs of the proband) in order to begin thiamine and biotin therapy as soon as possible in all individuals with biallelic SLC19A3 pathogenic variants, even those who are asymptomatic. Pregnancy management: Affected women should continue thiamine and biotin during pregnancy.

GENETIC COUNSELING:

BTBGD is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified.

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