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Whole exome sequencing reveals compound heterozygous mutations in SLC19A3 causing biotin-thiamine responsive basal ganglia disease

View Article: PubMed Central - PubMed

ABSTRACT

Biotin-thiamine responsive basal ganglia disease (BTBGD) is a rare metabolic condition caused by mutations in the SLC19A3 gene. BTBGD presents with encephalopathy and significant disease progression when not treated with biotin and/or thiamine. We present a patient of Mexican and European ancestry diagnosed with BTBGD found to have compound heterozygous frameshift mutations, one novel. Our report adds to the genotype-phenotype correlation, highlighting the clinical importance of considering SLC19A3 gene defects as part of the differential diagnosis for Leigh syndrome.

No MeSH data available.


Related in: MedlinePlus

Patient MRI Finding. a-c: Initial MRI obtained at 6 weeks of age revealed diffuse bilateral abnormal T2 signal in the basal ganglia, thalami and parieto-occipital white matter. Bilateral, well-circumscribed cyst-like lesions in the globus pallidi was observed (a). Abnormal T2 signal extended to the brain stem (b) and cerebellum (c). d-f: A repeat MRI obtained at 6 months of age demonstrated improvement of the T2 signal hyperintensities in the white matter of the brain (d), brainstem (e), and cerebellum (f). Diffuse brain atrophy was present. g-i: The final MRI, completed at 2.5 years of age, showed worsening of the white matter, basal ganglia, and thalamic abnormalities (g). Increased cystic lesions and atrophy are shown in Flair (h). Worsening of the cerebellar white matter hyperintensities in T2 was also noted (i).
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f0005: Patient MRI Finding. a-c: Initial MRI obtained at 6 weeks of age revealed diffuse bilateral abnormal T2 signal in the basal ganglia, thalami and parieto-occipital white matter. Bilateral, well-circumscribed cyst-like lesions in the globus pallidi was observed (a). Abnormal T2 signal extended to the brain stem (b) and cerebellum (c). d-f: A repeat MRI obtained at 6 months of age demonstrated improvement of the T2 signal hyperintensities in the white matter of the brain (d), brainstem (e), and cerebellum (f). Diffuse brain atrophy was present. g-i: The final MRI, completed at 2.5 years of age, showed worsening of the white matter, basal ganglia, and thalamic abnormalities (g). Increased cystic lesions and atrophy are shown in Flair (h). Worsening of the cerebellar white matter hyperintensities in T2 was also noted (i).

Mentions: At 6 weeks of age, regression of developmental milestones was noted and the patient was admitted to the hospital with lethargy, hypotonia, and poor feedings. Additionally, the exam showed a weak cry, horizontal nystagmus, and generalized brisk hyperreflexia. She had an episode of apnea, requiring intubation and mechanical ventilation. MRI of the brain revealed diffuse bilateral T2 signal abnormalities and cystic-like lesions in the globus pallidi (Fig. 1, a-c). Increased levels of lactate were seen on MRS.


Whole exome sequencing reveals compound heterozygous mutations in SLC19A3 causing biotin-thiamine responsive basal ganglia disease
Patient MRI Finding. a-c: Initial MRI obtained at 6 weeks of age revealed diffuse bilateral abnormal T2 signal in the basal ganglia, thalami and parieto-occipital white matter. Bilateral, well-circumscribed cyst-like lesions in the globus pallidi was observed (a). Abnormal T2 signal extended to the brain stem (b) and cerebellum (c). d-f: A repeat MRI obtained at 6 months of age demonstrated improvement of the T2 signal hyperintensities in the white matter of the brain (d), brainstem (e), and cerebellum (f). Diffuse brain atrophy was present. g-i: The final MRI, completed at 2.5 years of age, showed worsening of the white matter, basal ganglia, and thalamic abnormalities (g). Increased cystic lesions and atrophy are shown in Flair (h). Worsening of the cerebellar white matter hyperintensities in T2 was also noted (i).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121344&req=5

f0005: Patient MRI Finding. a-c: Initial MRI obtained at 6 weeks of age revealed diffuse bilateral abnormal T2 signal in the basal ganglia, thalami and parieto-occipital white matter. Bilateral, well-circumscribed cyst-like lesions in the globus pallidi was observed (a). Abnormal T2 signal extended to the brain stem (b) and cerebellum (c). d-f: A repeat MRI obtained at 6 months of age demonstrated improvement of the T2 signal hyperintensities in the white matter of the brain (d), brainstem (e), and cerebellum (f). Diffuse brain atrophy was present. g-i: The final MRI, completed at 2.5 years of age, showed worsening of the white matter, basal ganglia, and thalamic abnormalities (g). Increased cystic lesions and atrophy are shown in Flair (h). Worsening of the cerebellar white matter hyperintensities in T2 was also noted (i).
Mentions: At 6 weeks of age, regression of developmental milestones was noted and the patient was admitted to the hospital with lethargy, hypotonia, and poor feedings. Additionally, the exam showed a weak cry, horizontal nystagmus, and generalized brisk hyperreflexia. She had an episode of apnea, requiring intubation and mechanical ventilation. MRI of the brain revealed diffuse bilateral T2 signal abnormalities and cystic-like lesions in the globus pallidi (Fig. 1, a-c). Increased levels of lactate were seen on MRS.

View Article: PubMed Central - PubMed

ABSTRACT

Biotin-thiamine responsive basal ganglia disease (BTBGD) is a rare metabolic condition caused by mutations in the SLC19A3 gene. BTBGD presents with encephalopathy and significant disease progression when not treated with biotin and/or thiamine. We present a patient of Mexican and European ancestry diagnosed with BTBGD found to have compound heterozygous frameshift mutations, one novel. Our report adds to the genotype-phenotype correlation, highlighting the clinical importance of considering SLC19A3 gene defects as part of the differential diagnosis for Leigh syndrome.

No MeSH data available.


Related in: MedlinePlus