Biotin-responsive basal ganglia disease should be renamed biotin-thiamine-responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of 18 new cases

Abstract

BackgroundBiotin-responsive basal ganglia disease (BBGD) is an autosomal recessive neurometabolic disorder. It is characterized by sub acute encephalopathy with confusion, seizure, dysarthria and dystonia following a history of febrile illness. If left untreated with biotin, the disease can progress to severe quadriparesis and even death.MethodA retrospective chart review of 18 patients with BBGD from two tertiary institutions describing their clinical, magnetic resonance imaging and molecular findings was conducted.ResultEighteen children from 13 families seen over a period of nine years (2003–2012) were included. (Age range: 14month to 23 years, M: F: 1:1). The clinical features included sub acute encephalopathy, ataxia (n= 18), seizures (n= 13) dystonia (n=12) ,dysarthria (n= 9), quadriparesis and hyperreflexia (n=9). Magnetic resonance imaging demonstrated abnormal signal intensity with swelling in the basal ganglia during acute crises (n= 13/13) and atrophy of the basal ganglia and necrosis during follow up (n= 13/13). One-third of the present patients showed the recurrence of acute crises while on biotin therapy alone, but after the addition of thiamine, crises did not recur. All of the patients have a homozygous missense mutation in exon 5 of the SLC19A3 gene. The frequency of acute crises, delay in diagnosis and initiation of treatment significantly influenced the outcome. On follow up, four patients died, two had spastic quadriplegia, six had normal outcome and the rest had speech and motor dysfunctions. ConclusionClinicians should suspect BBGD in any child presenting with sub acute encephalopathy, abnormal movement and MRI findings as described above. Both biotin and thiamine are essential for disease management. Since biotin alone could not prevent the recurrence of crises in some patients, a more appropriate term to describe the disease would be biotin-thiamine-responsive basal ganglia disease (BTBGD).

Neuropathological characteristics of the brain in two patients with SLC19A3 mutations related to the biotin-thiamine-responsive basal ganglia disease

“…The natural history of the condition is quite well recognized, pointing to a remarkable clinical heterogeneity, even inside the same family and the wide range of severity and prognoses [6]. Recently this has been comprehensively reviewed [1,2].…”

“…Although in the literature there are numerous magnetic resonance imagining (MRI) series of SLC19A3 defect illustrating both specific changes in detail [6,17] and the response to specific treatment [1,2], only few reports focus on brain pathology in affected patients [15]. Herein, we present our unique autopsy findings ("walnut" appearance of the brain) in a Polish child who died many years ago, and in whom the underlying SLC19A3 homozygous mutation has been recently established by WES (whole-exome sequencing).…”

Biotin-Responsive Basal Ganglia Disease: Neuroimaging Features before and after Treatment

“…If left untreated with biotin, the disease can progress to severe quadriparesis and even death. 7 Biotin is a water-soluble vitamin belonging to the B complex and acts as a co-enzyme for the 4 important carboxylases in humans. 3 Biotin-dependent carboxylases catalyze the fixation of bicarbonate in organic acids and play crucial roles in the metabolism of fatty acids, amino acids, and glucose.…”

“…This combination of biotin and thiamine proved to prevent the recurrence of encephalopathy crisis. 7,9 It is important to recognize this disease because its symptoms may be reversed and the progression of its clinical course can be prevented simply by the administration of biotin and thiamine. 1,7 The purpose of this study is to assess the clinical and neuroimaging features of the disease on MR imaging before and after treatment with biotin and thiamine.…”

Biotin-responsive basal ganglia disease: a treatable differential diagnosis of Leigh syndrome

“…If untreated, the clinical course may be fatal (Tabarki et al 2013;Alfadhel et al 2013). Brain magnetic resonance imaging (MRI) typically demonstrates bilateral hyperintensity of caudate nucleus and putamen on T2-weighted sequences.…”