Single center experience of biotinidase deficiency: 259 patients and six novel mutations

Abstract

Background Biotinidase deficiency (BD) is an autosomal recessively inherited disorder of biotin recycling. It is classified into two levels based on the biotinidase enzyme activity: partial deficiency (10%-30% enzyme activity) and profound deficiency (0%-10% enzyme activity). The aims of this study were to evaluate our patients with BD, identify the spectrum of biotinidase (BTD) gene mutations in Turkish patients and to determine the clinical and laboratory findings of our patients and their follow-up period. Methods A total of 259 patients who were diagnosed with BD were enrolled in the study. One hundred and forty-eight patients were male (57.1%), and 111 patients were female (42.9%). Results The number of patients detected by newborn screening was 221 (85.3%). By family screening, 31 (12%) patients were diagnosed with BD. Seven patients (2.7%) had different initial complaints and were diagnosed with BD. Partial BD was detected in 186 (71.8%) patients, and the profound deficiency was detected in 73 (28.2%) patients. Most of our patients were asymptomatic. The most commonly found variants were p.D444H, p.R157H, c.98_104delinsTCC. The novel mutations which were detected in this study are p.D401N(c.1201G>A), p.A82G (c.245C>G), p.F128S(c.383T>C), c617_619del/TTG (p.Val207del), p.A287T(c.859G>A), p.S491H(c.1471A>G). The most common mutation was p.R157H in profound BD and p.D444H in partial BD. All diagnosed patients were treated with biotin. Conclusions The diagnosis of BD should be based on plasma biotinidase activity and molecular analysis. We determined the clinical and genetic spectra of a large group of patients with BD from Western Turkey. The frequent mutations in our study were similar to the literature. In this study, six novel mutations were described.

Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy

“…From our data, a remarkable overall incidence of 1:5,996 newborns with BD, combining partial and total deficiencies, emerged. Our incidence is significantly higher than previously reported in literature (5), even if recently some authors reported case studies identified by NBS with comparable incidences in different countries (2,3,13,21).…”

Clinical Findings and BTD Gene Molecular Analysis Results of Patients Presenting with Suspicion of Biotinidase Deficiency

“…Aile taramasında (Şekil 2) klinik olarak belirtiye sahip olmayan erkek kardeşinde de (III-5) biyotinidaz eksikliği ile uyumlu p.Asp444His, p.Ala171Thr mutasyonları saptandı. İki mutasyon taşıdığı halde asemptomatik olan benzer hastalar daha önce bildirilmiştir (2). Stresli dönemlerde saç dökülmesi, tırnak kırılması, dematit gibi ılımlı semptomlar tarifleyen annesi (II-8) ve kız kardeşlerinde (III-3 ve III-4) ise BTD geni mutasyonu saptanmadı.…”

“…Biyotin, dört karboksilaza (piruvat karboksilaz, propionil-CoA karboksilaz, metilkrotonil-CoA karboksilaz ve asetil-CoA karboksilaz) kovalent bağlanarak koenzim fonksiyonu gören suda çözünen bir vitamindir. Bu enzimler glukoneogenez, yağ asidi sentezi ve amino asit katabolizmasında rol alırlar (1,2). Biyotinidaz, biyotinin diyet proteinlerinden serbest bırakılarak emilmesinde ve aktif holokarboksilazlar gibi biotinil peptidlerden serbest bırakılarak yeniden biyotin döngüsüne katılmasında kritik bir rol oynayan enzimdir.…”

“…BTD geni kromozom 3q25 üzerinde bulunur ve 79 bp, 265 bp, 150 bp ve 1502 bp boyutlarında olmak üzere dört ekzon içerir. Bugüne kadar BTD geni tüm ekzon dizi analizi ile 150'den fazla farklı mutasyon tanımlanmıştır (2). Biyotinidaz eksikliği insidansı Dünyada 1:60.000, Türkiye'de 1:14.800 olup, Dünya ortalamasına göre 8 kat daha fazladır.…”

Treating epilepsy with options other than antiepileptic medications

“…Biotin supplementation in a dose ranging from 10 to 20 mg/d can improve the clinical picture, especially if started early. 12 Recurrent subacute encephalopathy is one of the importance early features of biotin-thiamine-responsive basal ganglia disease. It is an increasingly recognized condition and can lead to coma and death if not promptly treated.…”