AUTHOR=Van Winckel Géraldine , Ballhausen Diana , Wolf Barry , Procter Melinda , Mao Rong , Burda Patricie , Strambo Davide , Kuntzer Thierry , Tran Christel 

TITLE=Severe Distal Motor Involvement in a Non-compliant Adult With Biotinidase Deficiency: The Necessity of Life-Long Biotin Therapy

JOURNAL=Frontiers in Neurology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.516799

DOI=10.3389/fneur.2020.516799

ISSN=1664-2295

ABSTRACT=Biotinidase deficiency is an autosomal recessive disorder in which affected individuals are unable to recycle biotin. Untreated, children usually exhibit hypotonia, seizures, ataxia, developmental delay and/or hearing loss. Individuals diagnosed by newborn screening have an excellent prognosis with life-long biotin supplementation. We report a young adult diagnosed with profound biotinidase deficiency by newborn screening who was asymptomatic while on therapy. At 18 years of age, six months after voluntarily discontinuation of biotin, he developed a progressive distal muscle weakness. Molecular analysis of the BTD gene showed a pathogenic homozygous duplication c.1372_1373dupT (Li, 2014, c.1372_1373insT) p.(Cys458LeufsTer26). Despite 16 months since reintroduction of biotin, muscle strength only partially recovered. Transition to adulthood in chronic metabolic diseases is known to be associated with an increased risk for non-compliance. Neurological findings in this adult are similar to those described in others with adult-onset biotinidase deficiency. Long-term prognosis in non-compliant symptomatic adult with biotinidase deficiency likely depends on the delay and/or severity of intervening symptoms until reintroduction of biotin.