Biochemical and Clinical Characterization of a Patient with Partial Biotinidase Deficiency Carrying the Rare BTD c.690C>G (p.Phe230Leu) Variant: A Case Report

Biotinidase deficiency (BD) is an autosomal recessive inherited disorder in which the enzyme biotinidase (BTD) is totally or partially defective and the vitamin biotin is not recycled. More than 200 pathogenic variants in the BTD gene have been identified, causing complete or partial loss of enzyme activity and leading to profound or partial BD. Although the genotype–phenotype correlation is not fully defined, some genotypes are associated with profound forms and others with partial forms of BD. The patients with partial BD are mostly asymptomatic but symptoms may appear during stressful conditions such as infections. The patients with profound BD may present neurological problems, hearing loss, visual abnormalities, and organic aciduria, if not treated with biotin supplementation. BD is included in most newborn screening programs (NBS). Screening test relies on measurement of BTD enzyme activity in dried blood spot (DBS), followed by a plasma BTD assay and BTD molecular analysis as confirmatory test. We describe a male newborn with partial BD identified through the newborn screening program. Low BTD activity on DBS was detected; BTD molecular analysis showed the proband to be compound heterozygous for the c.1270G>C (p.Asp424His) mild known variant, and for the rare variant c.690C>G (p.Phe230Leu) previously identified by our group. In this study, we provide the biochemical and clinical characterization of a patient carrying the c.690C>G (p.Phe230Leu) variant, and our findings support a possible contribution of this variant to the partial BD phenotype.