Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations.
OBJECTIVE
To report the first 2 European cases of biotin-responsive basal ganglia disease and novel SLC19A3 mutations.


METHODS
Case reports.


METHODS
University hospital. Patients A 33-year-old man and his 29-year-old sister, both of Portuguese ancestry, presented with recurrent episodes of encephalopathy. Between episodes patients exhibited generalized dystonia, epilepsy, and bilateral hyperintensities of the caudate and putamen.


METHODS
Clinical and radiologic findings.


RESULTS
Administration of high doses of biotin or of a combination of biotin and thiamine during encephalopathies resulted in spectacular clinical and radiologic improvement in both patients. Sequencing of the SLC19A3 disclosed 2 novel mutations, both of which created premature stop codons in the protein sequence of hTHTR2.


CONCLUSIONS
This study demonstrates that biotin-responsive basal ganglia disease is a panethnic condition. A therapeutic trial with high doses of biotin and thiamine seems mandatory in every unexplained encephalopathy with bilateral lesions of putamen and caudate nuclei.
Debs
Rabab
R
Federation of Nervous System Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital de la Salpêtrière, Université Pierre et Marie Curie, Paris CEDEX 13, France.
Depienne
Christel
C
Rastetter
Agnès
A
Bellanger
Agnès
A
Degos
Bertrand
B
Galanaud
Damien
D
Keren
Boris
B
Lyon-Caen
Olivier
O
Brice
Alexis
A
Sedel
Frédéric
F
D000328:Adult; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001480:Basal Ganglia Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D001710:Biotin / Q000494:pharmacology* / Q000627:therapeutic use; D001928:Brain Diseases, Metabolic / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004421:Dystonia / Q000235:genetics; D004827:Epilepsy / Q000235:genetics; D005060:Europe / Q000208:ethnology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011174:Portugal / Q000208:ethnology; D013831:Thiamine / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000494:pharmacology* / Q000627:therapeutic use; D044465:White People / Q000235:genetics
D005819:Genetic Markers; D026901:Membrane Transport Proteins; C492291:SLC19A3 protein, human; D014803:Vitamin B Complex; D001710:Biotin; D013831:Thiamine