Identification and Characterization of BTD Gene Mutations in Jordanian Children with Biotinidase Deficiency.

Laith N. AL-Eitan,Rame Khasawneh,Mamoon Al-Abed,Wajdi Amayreh,Hanan Aljamal,Hazem Haddad,Zaher Jaradat,Tamara Rawashdeh,Yazan Haddad,Kifah Alqa’qa’

doi:10.3390/jpm10010004

Abstract

Biotinidase deficiency is an autosomal recessive metabolic disorder whose diagnosis currently depends on clinical symptoms and a biotinidase enzyme assay. This study aimed to investigate the mutational status and enzymatic activity of biotinidase deficiency in seven unrelated Jordanian families including 10 patients and 17 healthy family members. Amplified DNA was analyzed by the automated Sanger sequencing method, and the enzymatic assay was performed using a colorimetric assessment. Biotinidase level was significantly lower (p < 0.001) in BTD children compare to their non-affected family members. Genetic sequencing revealed six different mutations in Jordanian patients. One mutation was novel and located in exon 4, which could be a prevalent mutation for biotinidase deficiency in the Jordanian population. Identification of these common mutations and combing the enzymatic activity with genotypic data will help clinicians with regard to better genetic counseling and management through implementing prevention programs in the future.

Highlights

The biotinidase enzyme separates biotin from dietary protein-bound sources, and it is responsible for biotin recycling [1,2,3]
Clinical characteristics related to the biotinidase deficiency were observed in all patients with variation in the associated neurological and dermatological traits (Table 2)
No. 6 showed an rs80338684 mutation in its three affected children. This 7-bp deletion/3-bp insertion in exon 3 (98-104del7ins3) caused a frameshift terminated with a stop codon that may result in a truncated protein

Summary

Introduction

The biotinidase enzyme separates biotin from dietary protein-bound sources, and it is responsible for biotin recycling [1,2,3]. Biotinidase deficiency is an inherited autosomal recessive disorder where the biotinidase enzyme activity is blocked, resulting in the inability to release biotin from the diet and recycling this vitamin [1,2,4,5,6]. Symptoms of the disease begin to appear at the first 2–3 months of. Med. 2020, 10, 4 life or later throughout childhood [7,8]. The deficiency can be classified into profound and partial biotinidase deficiency based on the enzyme level measurement [1,9]

Objectives

Methods

Results

Discussion

Conclusion