Biotin-thiamine responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of cases in Kuwait with novel variants

Orphanet Journal of Rare Diseases

Research

Mariam Ayed¹  Rasha Alsafi²  Nawal Makhseed³  Asma Al-Tawari⁴  Dina Ramadan⁴  Maryam Aburezq⁵  Magdy Shafik⁵  Hind Alsharhan⁶  Abrar Hayat⁷  Omar Abdelaty⁸  Fatima Dashti⁹  Buthaina Albash^1,10  Reem Elshafie^1,10  Laila Bastaki^1,10  Ahmad Alahmad^1,10  Dana Marafi^1,11 

[1] Department of Neonatology, Maternity Hospital, Ministry of Health, Shuwaikh, Kuwait;Department of Pediatrics, Adan Hospital, Ministry of Health, Hadiya, Kuwait;Department of Pediatrics, Al-Jahra Hospital, Ministry of Health, Al-Jahra, Kuwait;Department of Pediatrics, Al-Sabah Hospital, Ministry of Health, Shuwaikh, Kuwait;Department of Pediatrics, Farwaniya Hospital, Ministry of Health, Sabah Al-Nasser, Kuwait;Department of Pediatrics, Farwaniya Hospital, Ministry of Health, Sabah Al-Nasser, Kuwait;Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait;Department of Pediatrics, Faculty of Medicine, Health Sciences Centre, Kuwait University, P.O. Box 24923, Safat 13110, Postal Code 90805, Jabriya, Kuwait;Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Department of Radiology, Adan Hospital, Ministry of Health, Hadiya, Kuwait;Department of Radiology, Farwaniya Hospital, Ministry of Health, Sabah Al-Nasser, Kuwait;Department of Radiology, Ibn Sina Hospital, Ministry of Health, Shuwaikh, Kuwait;Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait;Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait;Department of Pediatrics, Faculty of Medicine, Health Sciences Centre, Kuwait University, P.O. Box 24923, Safat 13110, Postal Code 90805, Jabriya, Kuwait;

关键词: Biotin-thiamine-responsive;    Basal ganglia;    SLC19A3;    Neurometabolic;    Encephalopathy;    Genetic;   

DOI  :  10.1186/s13023-023-02888-y

 received in 2023-02-20, accepted in 2023-08-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundBiotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive neurometabolic disorder that is caused by biallelic pathogenic SLC19A3 variants and is characterized by subacute encephalopathy associated with confusion, convulsions, dysphagia, dysarthria, or other neurological manifestations.MethodsA retrospective review of the data registry in Kuwait Medical Genetics Center for all cases diagnosed clinically and radiographically and confirmed genetically with BTBGD.ResultsTwenty one cases from 13 different families were diagnosed with BTBGD in Kuwait. Most cases (86%) presented with confusion, dystonia, convulsions, or dysarthria, while three individuals were diagnosed pre-symptomatically during familial targeted genetic screening. Symptoms resolved completely within 2-week of treatment in two-thirds of the symptomatic cases but progressed in six of them to a variety of severe symptoms including severe cogwheel rigidity, dystonia and quadriparesis due to delayed presentation and management. Neuroradiological findings of the symptomatic cases revealed bilateral central changes in the basal ganglia. Two novel homozygous missense SLC19A3 variants were detected in a Kuwaiti and a Jordanian individuals, in addition to the previously reported Saudi founder homozygous variant, c.1264A > G; p.(Thr422Ala) in the remaining cases. Age of diagnosis ranged from newborn to 32 years, with a median age of 2–3 years. All cases are still alive receiving high doses of biotin and thiamine.ConclusionThis is the first study reporting the phenotypic and genotypic spectrum of 21 individuals with BTBGD in Kuwait and describing two novel SLC19A3 variants. BTBGD is a treatable neurometabolic disease that requires early recognition and treatment initiation. This study highlights the importance of performing targeted molecular testing of the founder variant in patients presenting with acute encephalopathy in the region.

【 授权许可】

CC BY   
© Institut National de la Santé et de la Recherche Médicale (INSERM) 2023

【 图 表 】

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