Outcome in patients with profound biotinidase deficiency: relevance of newborn screening

Dev Med Child Neurol. 2004 Jul;46(7):481-4. doi: 10.1017/s0012162204000799.


Profound biotinidase deficiency (PBD) is an autosomal recessively inherited disorder of biotin metabolism, which can be detected by newborn screening and treated with biotin supplementation. Children were investigated in whom PBD was detected by newborn screening and who were treated presymptomatically, or who were not screened but were diagnosed and treated after experiencing initial clinical symptoms (symptomatic children). In a follow-up of our study group, differences in development, social and behavioural adaptation, and signs of residual impairment were examined. Parents and physicians of children with PBD completed questionnaires which included the Child Behavior Checklist and Vineland Adaptive Behavior Scales. Information was obtained for 37 children (24 males, 13 females; median age at recruitment 6 years 8 months, range to 6 months-20 years; median length of follow-up 6 years 6 months, range 5 months to 18 years 3 months). All 11 symptomatic children had residual enzyme activity of <1%, or variants of the Michaelis-Menten constant which were not detected by newborn screening. Some symptomatic children showed residual impairments: hearing impairment (n=2), optic atrophy (n=2), both hearing impairment and optic atrophy (n=2). In addition, symptomatic children had a higher risk of delayed motor and speech development. No child with PBD detected by newborn screening (n=25) had auditory or visual loss; and milestones of speech development and motor skills were reached at an appropriate age. There was no significant difference in social adaptation or behavioural problems between symptomatic and asymptomatic children. Symptomatic children often have developmental delay and are at risk of irreversible damage to auditory, visual, or central nervous functions; whereas children with PBD (established presymptomatically following newborn screening) treated with biotin supplementation, do not experience these effects.

MeSH terms

  • Adaptation, Psychological
  • Adolescent
  • Adult
  • Biotin / metabolism
  • Biotin / therapeutic use
  • Biotinidase Deficiency / drug therapy*
  • Biotinidase Deficiency / epidemiology*
  • Biotinidase Deficiency / genetics
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Hearing Disorders / diagnosis
  • Hearing Disorders / epidemiology
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Motor Skills Disorders / diagnosis
  • Motor Skills Disorders / epidemiology
  • Neonatal Screening / methods*
  • Optic Atrophy / diagnosis
  • Optic Atrophy / epidemiology
  • Outcome Assessment, Health Care
  • Severity of Illness Index
  • Social Adjustment
  • Speech Disorders / diagnosis
  • Speech Disorders / epidemiology


  • Biotin