ABSTRACT
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.
Subject(s)
Basal Ganglia Diseases/diagnosis , Basal Ganglia Diseases/genetics , Membrane Transport Proteins/genetics , Mutation , Basal Ganglia Diseases/drug therapy , Biotin/therapeutic use , Child, Preschool , Genetic Testing , Humans , Male , Pedigree , Saudi Arabia , Thiamine/therapeutic use , Vitamin B Complex/therapeutic useABSTRACT
OBJECTIVE: To determine how benzodiazepine (BZD) sensitivity testing might be utilized to choose potentially useful antiepileptic drugs. METHODS: A retrospective audit of BZD sensitivity testing was carried out on 76 difficult pediatric epileptic cases that attended the Pediatric Neurology services at The Royal Hospital for Sick Children Edinburgh, Scotland from February 2005 to February 2006. The causes and types of epilepsy varied widely, as well as the encephalographic (EEG) findings. The EEG changes post-test are categorized according to the response to BZDs into "complete," "intermediate," "paradoxical" and "absent response." Similarly, the clinical outcomes after changing their antiepileptic medications have different ranges of clinical improvement from "definitive," "partial" and "no improvement." RESULTS: The largest percentages of definitive improvement are seen in those with complete response. The percentage with clinical improvement tends to decrease a) with increasing numbers and amplitudes of spikes that are resistant to the action of BZD, and b) when there is a paucity of, and different distribution of fast rhythms, indicating non-viability of cortical tissues. High spike density regions in the EEG pre-test that correlate with a specific pathology, and are found post-test to be devoid of fast rhythms, may indicate focally damaged gamma-aminobutyric acid receptor areas. CONCLUSION: The BZD sensitivity testing may influence the choice of anticonvulsants in the management of epilepsy.
