Late Onset Subacute Profound Biotinidase Deficiency Caused by a Novel Homozygous Variant c.466-3T>G in the BTD Gene

Abstract

Biotinidase deficiency (BD) is an autosomal recessive disorder caused by bi-allelic mutation in the BTD gene. Clinical manifestations in BD mainly depends on residual biotinidase enzyme activity, although there are some exceptions. Broadly BD disorders are classified as profound BD and partial BD. Further profound BD can be early onset, late onset, and sometimes may be asymptomatic. Clinically late-onset profound BD can present with spectrum of manifestations ranging from single organ to multiple organ involvement, typically affecting function of brain, eye, ear, and skin. Here, a first-born child to consanguineous parents with late-onset profound BD presenting with hyperventilation secondary to lactic acidosis, hypotonia, evolving spasticity, and abnormal neuroimaging findings caused by novel homozygous variant, c.466-3T>G in the BTD gene is reported.

Biallelic loss-of-function variations in BTD cause profound biotinidase deficiency in an Indian patient

“…This study adds to the growing body of Indian cases with a detailed analysis of novel biallelic variations (c.903G > A and c.946C > T) in the BTD gene. Our ndings are similar to previous reports in India describing a case with a c.466-3T > G mutation causing profound BD and another with a c.133C > T (p.H447Y) mutation presenting as recurrent myelopathy [34,35]. These cases highlight the importance of BTD gene analysis alongside enzymatic activity assessment for a more comprehensive understanding of the genetic basis and potential for future genetic counseling to prevent recurrence in families.…”