An unusually mild case of biotin-thiamine-responsive basal ganglia disease
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SUBMITTER: Lail G
PROVIDER: S-EPMC10694770 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:IntroductionBiotin-thiamine responsive basal ganglia disease (BTBGD) is a rare autosomal recessive neurometabolic disorder characterized by diverse and variable phenotypic features, which can make diagnosis challenging. However, prompt treatment with thiamine and biotin can effectively manage the condition. Diagnosis relies on the identification of biallelic pathogenic variants in the SLC19A3 gene. This case report describes two novel variants of uncertain significance in the SLC19A3 gene, which may be correlated with the phenotypic manifestations of BTBGD.Case presentationOur case is a 7-month-old female infant who presented with a 3-week history of irritability, altered behavior, and refusal of newly introduced solid foods. Symptoms started with an upper respiratory tract infection, followed by lethargy, floppiness, and abnormal movements. The patient was admitted to the pediatric ward with a broad differential diagnosis. Extensive laboratory evaluations revealed lactic acidosis. MRI brain showed symmetric restricted diffusion affecting the bilateral basal ganglia, thalami, and cortical regions. Whole genome sequencing identified biallelic variants of the SLC19A3: a c.1364T>G p.Met455Arg missense variant in the maternal allele and a 2.3 kb deletion of intron 3 of the paternal allele. Both variants were identified as variants of uncertain significance. However, given the clinical picture, MRI brain findings, resolution of symptoms with empiric biotin and thiamine supplementation, and biallelic SLC19A3 variants of unknown significance, the patient most likely suffers from BTBGD. Patient continues to show sustained developmental progress on biotin and thiamine supplementation.ConclusionThis case highlights the fact that genetic testing remains a vital but improvable tool for the diagnosis of BTBGD. As of yet, genetic testing and diagnosis of BTBGD continues to be limited by the knowledge of which SLC19A3 variants are established to be pathogenic variants. Thus, further research is required to study other SCL19A3 variants of unknown significance to further improve genetic testing and diagnosis of BTBGD in the future.
| S-EPMC11781812 | biostudies-literature
Project description:Biotin-thiamine-responsive basal ganglia disease is a devastating autosomal recessive inherited neurological disorder. We conducted a retrospective chart review of all patients with biotin-thiamine-responsive basal ganglia disease who underwent a formal psychological assessment. Six females and 3 males were included. Five patients (56%) had an average IQ, two patients (22%) had mild delay, and two (22%) had severe delay. A normal outcome was directly related to the time of diagnosis and initiation of treatment. Early diagnosis and immediate commencement of treatment were associated with a favorable outcome and vice versa. The most affected domain was visual motor integration, while understanding and mathematical problem-solving were the least affected. In summary, this is the first study discussing the psychological assessment of patients with biotin-thiamine-responsive basal ganglia disease. The results of this study alert clinicians to consider prompt initiation of biotin and thiamine in any patient presenting with neuroregression and a basal ganglia lesion on a brain magnetic resonance imaging.
| S-EPMC5604839 | biostudies-literature
Project description:BackgroundBiotin-thiamine-responsive basal ganglia disease (BTBGD) is an autosomal recessive neurometabolic disorder associated with pathogenic variants in SLC19A3 gene. The clinical picture includes symptoms of subacute encephalopathy (e.g. confusion, dysphagia, dysarthria, and seizures), which respond very well to early treatment with thiamine and biotin.MethodA retrospective review of clinical characteristics, magnetic resonance imaging and molecular findings in 3 patients with BTBGD.ResultsThe first symptoms in all patients occurred at 12-24 months of age and they had subacute encephalopathy, ataxia and dystonia. The baseline magnetic resonance imaging demonstrated abnormal signal intensity in the basal ganglia with atrophy and necrosis of the basal ganglia during follow-up in two patients. One patient was diagnosed and the treatment was initiated after a long period from symptoms onset and he is currently severely affected, with dystonia, quadriparesis and seizures. The other two patients were diagnosed early in life and are currently stable on treatment, without the clinical symptoms. Genetic testing demonstrated pathogenic variants in SLC19A3 gene.ConclusionTo avoid diagnostic errors and delayed or incorrect treatment, BTBGD must be recognized early. Adequate prompt treatment gives the chance of significant clinical improvement. Unexplained encephalopathy and MRI abnormalities including bilateral abnormal signal in the basal ganglia should alert the clinician to consider BTBGD in the differential, and the treatment with biotin and thiamine should be introduced immediately.
| S-EPMC8488057 | biostudies-literature
Project description:Background:Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare treatable autosomal recessive neurometabolic disorder characterized by progressive encephalopathy that eventually leads to severe disability and death if not treated with biotin and thiamine supplements. Objectives:We aimed to determine the optimal management of BTBGD presenting in acute encephalopathic episodes. Method:Case report. Results:An 8-year-old girl born to consanguineous parents was diagnosed with BTBGD at the age of 3 years after presenting with acute encephalopathy and ataxia. The patient was treated with biotin and thiamine, and the family was instructed to continue these medications for life. When she was 7 years old, her supplements were stopped for 2 weeks for social reasons. Afterward, the patient began to have tremor in both hands and an unsteady gait. The family then resumed the medications at the usual dosages. However, the patient remained symptomatic. The patient was admitted with acute BTBGD because of discontinuation of medications. The patient's condition was then managed with high doses of intravenous thiamine and oral biotin. She showed gradual improvement after 48 hours. She was then discharged home 1 week later with residual mild upper and lower limb tremor, as well as right lower limb dystonia. Further follow-up showed a good neurological condition with no apparent long-term sequel. The family was further educated about the importance of strict compliance. Conclusion:Patients with BTBGD should remain on lifelong treatment with thiamine and biotin. For those who present with acute relapse, we recommend inpatient treatment with high doses of intravenous thiamine and oral biotin. Further clinical research is required to determine the optimal doses and durations.
| S-EPMC5946631 | biostudies-literature
Project description:BACKGROUND: Biotin-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. METHOD: A retrospective chart review of 18 patients with BBGD from two tertiary institutions describing their clinical, magnetic resonance imaging and molecular findings was conducted. RESULT: Eighteen 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. CONCLUSION: Clinicians 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).
| S-EPMC3691666 | biostudies-literature
Project description: Not available
| S-EPMC4844240 | biostudies-literature
Project description:BACKGROUND:Biotin-thiamine-responsive basal ganglia disease (BTRBGD) is a neurometabolic autosomal recessive (AR) disorder characterized by subacute encephalopathy with confusion, convulsions, dysarthria, and dystonia. The disease is completely reversible if treated early with biotin and thiamine, and can be fatal if left untreated.We herein present our experience with in an extended family study of an index case of BTRBGD aiming to support its AR mode of inheritance, diagnose asymptomatic and missed symptomatic cases, and provide family screening with proper genetic counseling. METHODS:An index case of BTRBGD and his family underwent thorough clinical and radiological assessment along with genetic molecular testing. RESULTS:Two-and-half years old Saudi male child whose parents are consanguineous fulfilled the clinical and magnetic resonance imaging (MRI) criteria of BTRBGD. He was proved by molecular genetic testing to have homozygous mutation of c.1264A>G (p.Thr422Ala) in the SLC19A3 gene of BTRBGD. Extended clinical, radiological, and genetic family study revealed 2 affected members: a neglected symptomatic cousin with subtle neurological affection and an asymptomatic brother carrying the disease mutation in homozygous status. Heterozygous pattern was detected in his parents, his grandma and grandpa, his aunt and her husband, 2 siblings, and 1 cousin while 1 sibling and 2 cousins were negative to this mutation.Treatment of the patient and his diseased cousin with biotin and thiamine was initiated with gradual improvement of symptoms within few days. Treatment of his asymptomatic brother was also initiated. CONCLUSION:BTRBGD requires high index of suspicion in any child presenting with unexplained subacute encephalopathy, abnormal movement, and characteristic MRI findings. Extended family study is crucial to diagnose asymptomatic diseased cases and those with subtle neurological symptoms.
| S-EPMC5059037 | biostudies-literature
Project description:Mutations in the gene SLC19A3 result in thiamine metabolism dysfunction syndrome 2, also known as biotin-thiamine-responsive basal ganglia disease (BTBGD). This neurometabolic disease typically presents in early childhood with progressive neurodegeneration, including confusion, seizures, and dysphagia, advancing to coma and death. Treatment is possible via supplement of biotin and/or thiamine, with early treatment resulting in significant lifelong improvements. Here we report two siblings who received a refined diagnosis of BTBGD following whole-genome sequencing. Both children inherited compound heterozygous mutations from unaffected parents; a missense single-nucleotide variant (p.G23V) in the first transmembrane domain of the protein, and a 4808-bp deletion in exon 1 encompassing the 5' UTR and minimal promoter region. This deletion is the smallest promoter deletion reported to date, further defining the minimal promoter region of SLC19A3 Unfortunately, one of the siblings died prior to diagnosis, but the other is showing significant improvement after commencement of therapy. This case demonstrates the power of whole-genome sequencing for the identification of structural variants and subsequent diagnosis of rare neurodevelopmental disorders.
| S-EPMC5701311 | biostudies-literature
Project description: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.
| S-EPMC5121344 | biostudies-literature
Project description:Biotin-responsive basal ganglia disease (BBGD) with SLC19A3 mutation was first reported in 1998, and over 30 mutations have been reported. We report a neonatal BBGD case with sudden-onset feeding difficulty and impaired consciousness. Encephalopathy resolved after the initiation of biotin and thiamine treatment. Genetic testing revealed a novel heterozygous mutation [c.384_387del, p.Tyr128fs];[c.265 A > C, p.Ser89Arg] in SLC19A3. Early treatment for BBGD is essential, especially with onset in the neonatal or early infancy period.
| S-EPMC9522647 | biostudies-literature