Biotinidase Deficiency Treatment & Management
- Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD more...
Therapy for biotinidase deficiency is oral biotin, typically prescribed at a starting dose of 5-10 mg/d. Treatment is with free biotin. Bound biotin contained in oral multivitamin supplements does not treat the body deficiency.
Some patients require higher daily doses of free biotin. If the enzymatic defect is present but a healthy clinical response does not occur with lower doses, a high-dose therapy is considered (up to 40 mg/d).
Treatment with free biotin is lifelong in patients with profound deficiency. Patients with a partial deficiency (10%-25% activity remaining) may not require lifelong treatment. Both patient populations, however, require knowledgeable continuity of care to address ongoing medical care and treatment approach.
Children with residual neurologic disease may require medical interventions for developmental delay, spasticity, and bulbar dysfunction, in addition to oral biotin treatment. Spasticity and dystonia associated with inborn errors of metabolism have been treated with intrathecal baclofen and neurotoxins.
A pediatric neurologist, metabolic disorder specialist, and geneticist should assist in the patient’s workup and evaluation.
A pediatric neurologist and a pediatrician skilled in the evaluation of a child who is delayed and neurologically impaired should establish continuity of care and perform follow-up examinations, as well as procedures to document residual neurological insult. Children with residual neurologic injury as noted with spasticity or dystonia should receive ongoing physical therapy to prevent long-term orthopedic deterioration.
A medical genetics team, including a genetic counselor, should be referred to explain the genetics of biotinidase deficiency and to offer support and resources to patients and family members.
Quest Diagnostics. Biotinidase Deficiency. Available at http://www.questdiagnostics.com/testcenter/testguide.action?dc=TH_Biotinidase.
Gompertz D, Draffan GH, Watts JL, Hull D. Biotin-responsive beta-methylcrotonylglycinuria. Lancet. 1971 Jul 3. 2(7714):22-4. [Medline].
Wolf B, Hsia YE, Sweetman L, et al. Multiple carboxylase deficiency: clinical and biochemical improvement following neonatal biotin treatment. Pediatrics. 1981 Jul. 68(1):113-8. [Medline].
Wolf B, Heard GS, Weissbecker KA, et al. Biotinidase deficiency: initial clinical features and rapid diagnosis. Ann Neurol. 1985 Nov. 18(5):614-7. [Medline].
Tsao CY, Kien CL. Complete biotinidase deficiency presenting as reversible progressive ataxia and sensorineural deafness. J Child Neurol. 2002 Feb. 17(2):146. [Medline].
Chedrawi AK, Ali A, Al Hassnan ZN, Faiyaz-Ul-Haque M, Wolf B. Profound biotinidase deficiency in a child with predominantly spinal cord disease. J Child Neurol. 2008 Sep. 23(9):1043-8. [Medline].
Dahiphale R, Jain S, Agrawal M. Biotinidase deficiency. Indian Pediatr. 2008 Sep. 45(9):777-9. [Medline].
National Center for Biotechnology Information. Biotin. Available at http://ttp://pubchem.ncbi.nlm.nih.gov/rest/chemical/biotin.
Zempleni J, Wijeratne SS, Hassan YI. Biotin. Biofactors. 2009 Jan-Feb. 35(1):36-46. [Medline].
Wolf B. Worldwide survey of neonatal screening for biotinidase deficiency. J Inherit Metab Dis. 1991. 14 (6):923-7. [Medline].
Cowan TM, Kazerouni NN, Dharajiya N, Lorey F, Roberson M, Hodgkinson C, et al. Increased incidence of profound biotinidase deficiency among Hispanic newborns in California. Mol Genet Metab. 2012 Aug. 106 (4):485-7. [Medline].
Wolf B. Biotinidase Deficiency. Available at http://www.ncbi.nlm.nih.gov/books/NBK1322/.
Heard GS, Annison EF. Gastrointestinal absorption of vitamin B-6 in the chicken (Gallus domesticus). J Nutr. 1986 Jan. 116(1):107-20. [Medline].
National Newborn Screening Status Report. Available at http://genes-r-us.uthscsa.edu/sites/genes-r-us/files/nbsdisorders.pdf.
Medical Home Portal. Biotinidase deficiency. Available at http://www.medicalhomeportal.org/newborn/biotinidase-deficiency.
Venkataraman V, Balaji P, Panigrahi D, Jamal R. Biotinidase deficiency in childhood. Neurol India. 2013 Jul-Aug. 61(4):411-3. [Medline].
Thodi G, Schulpis KH, Molou E, Georgiou V, Loukas YL, Dotsikas Y, et al. High incidence of partial biotinidase deficiency cases in newborns of Greek origin. Gene. 2013 Jul 25. 524(2):361-2. [Medline].
Burton BK, Roach ES, Wolf B, Weissbecker KA. Sudden death associated with biotinidase deficiency. Pediatrics. 1987 Mar. 79(3):482-3. [Medline].
Welling DB. Long-term follow-up of hearing loss in biotinidase deficiency. J Child Neurol. 2007 Aug. 22(8):1055. [Medline].
Salbert BA, Pellock JM, Wolf B. Characterization of seizures associated with biotinidase deficiency. Neurology. 1993 Jul. 43(7):1351-5. [Medline].
Wolf B, Spencer R, Gleason T. Hearing loss is a common feature of symptomatic children with profound biotinidase deficiency. J Pediatr. 2002 Feb. 140(2):242-6. [Medline].
Tokatli A, Coşkun T, Ozalp I. Biotinidase deficiency with neurological features resembling multiple sclerosis. J Inherit Metab Dis. 1997 Sep. 20 (5):707-8. [Medline].
Wolf B, Pomponio RJ, Norrgard KJ, et al. Delayed-onset profound biotinidase deficiency. J Pediatr. 1998 Feb. 132(2):362-5. [Medline].
Wolf B. Biotinidase deficiency: "if you have to have an inherited metabolic disease, this is the one to have". Genet Med. 2012 Jan 5. [Medline].
Desai S, Ganesan K, Hegde A. Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients. Pediatr Radiol. 2008 Aug. 38(8):848-56. [Medline].
Armstrong RW, Steinbok P, Cochrane DD, Kube SD, Fife SE, Farrell K. Intrathecally administered baclofen for treatment of children with spasticity of cerebral origin. J Neurosurg. 1997 Sep. 87(3):409-14. [Medline].
Wolf B, Heard GS, Jefferson LG, Proud VK, Nance WE, Weissbecker KA. Clinical findings in four children with biotinidase deficiency detected through a statewide neonatal screening program. N Engl J Med. 1985 Jul 4. 313(1):16-9. [Medline].
[Guideline] Michigan Quality Improvement Consortium. Routine preventive services for infants and children (birth-24 months). 2007 May. [Full Text].
Wolf B. Biotinidase deficiency: "if you have to have an inherited metabolic disease, this is the one to have". Genet Med. 2012 Jun. 14(6):565-75. [Medline].
Ataman M, Sozeri B, Ozalp I. Biotinidase deficiency: a rare cause of laryngeal stridor. Int J Pediatr Otorhinolaryngol. 1992 May. 23(3):281-4. [Medline].
Baumgartner ER, Suormala TM, Wick H, et al. Biotinidase deficiency: a cause of subacute necrotizing encephalomyelopathy (Leigh syndrome). Report of a case with lethal outcome. Pediatr Res. 1989 Sep. 26(3):260-6. [Medline].
Bousounis DP, Camfield PR, Wolf B. Reversal of brain atrophy with biotin treatment in biotinidase deficiency. Neuropediatrics. 1993 Aug. 24(4):214-7. [Medline].
Colamaria V, Burlina AB, Gaburro D, et al. Biotin-responsive infantile encephalopathy: EEG-polygraphic study of a case. Epilepsia. 1989 Sep-Oct. 30(5):573-8. [Medline].
Grapp M, Just IA, Linnankivi T, Wolf P, Lücke T, Häusler M. Molecular characterization of folate receptor 1 mutations delineates cerebral folate transport deficiency. Brain. 2012 Jul. 135(Pt 7):2022-31. [Medline].
Honavar M, Janota I, Neville BG, Chalmers RA. Neuropathology of biotinidase deficiency. Acta Neuropathol (Berl). 1992. 84(4):461-4. [Medline].
Kalayci O, Coskun T, Tokatli A, et al. Infantile spasms as the initial symptom of biotinidase deficiency. J Pediatr. 1994 Jan. 124(1):103-4. [Medline].
Kalkanoglu HS, Dursun A, Tokatli A, et al. A boy with spastic paraparesis and dyspnea. J Child Neurol. 2004 May. 19(5):397-8. [Medline].
Kimura M, Fukui T, Tagami Y, et al. Normalization of low biotinidase activity in a child with biotin deficiency after biotin supplementation. J Inherit Metab Dis. 2003. 26(7):715-9. [Medline].
Mardach R, Zempleni J, Wolf B, et al. Biotin dependency due to a defect in biotin transport. J Clin Invest. 2002 Jun. 109(12):1617-23. [Medline].
Mock DM. Skin manifestations of biotin deficiency. Semin Dermatol. 1991 Dec. 10(4):296-302. [Medline].
Moslinger D, Stockler-Ipsiroglu S, Scheibenreiter S, et al. Clinical and neuropsychological outcome in 33 patients with biotinidase deficiency ascertained by nationwide newborn screening and family studies in Austria. Eur J Pediatr. 2001 May. 160(5):277-82. [Medline].
Neto EC, Schulte J, Rubim R, et al. Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations. Braz J Med Biol Res. 2004 Mar. 37(3):295-9. [Medline].
Ozand PT, Gascon GG, Al Essa M, et al. Biotin-responsive basal ganglia disease: a novel entity. Brain. 1998 Jul. 121 (Pt 7):1267-79. [Medline].
Perez-Monjaras A, Cervantes-Roldan R, Meneses-Morales I, et al. Impaired biotinidase activity disrupts holocarboxylase synthetase expression in late onset multiple carboxylase deficiency. J Biol Chem. 2008 Dec 5. 283(49):34150-8. [Medline].
Pidcock FS. Botulinum toxin type A treatment in neurogenetic syndromes. Pediatr Rehabil. 2005 Oct-Dec. 8(4):298-302. [Medline].
Reed JJ, Rupp T. Emergency department presentation of biotinidase deficiency: fulminant sepsis in a 4-year-old Hispanic male. Pediatr Emerg Care. 2004 Jan. 20(1):37-9. [Medline].
Riudor E, Vilaseca MA, Briones P, et al. Requirement of high biotin doses in a case of biotinidase deficiency. J Inherit Metab Dis. 1989. 12(3):338-9. [Medline].
Straussberg R, Saiag E, Harel L, et al. Reversible deafness caused by biotinidase deficiency. Pediatr Neurol. 2000 Sep. 23(3):269-70. [Medline].
Weber P, Scholl S, Baumgartner ER. Outcome in patients with profound biotinidase deficiency: relevance of newborn screening. Dev Med Child Neurol. 2004 Jul. 46(7):481-4. [Medline].
Williams ML, Packman S, Cowan MJ. Alopecia and periorificial dermatitis in biotin-responsive multiple carboxylase deficiency. J Am Acad Dermatol. 1983 Jul. 9(1):97-103. [Medline].
Wiznitzer M, Bangert BA. Biotinidase deficiency: clinical and MRI findings consistent with myelopathy. Pediatr Neurol. 2003 Jul. 29(1):56-8. [Medline].
Wolf B. Biotinidase Deficiency: New Directions and Practical Concerns. Curr Treat Options Neurol. 2003 Jul. 5(4):321-328. [Medline].
Wolf B, Grier RE, Allen RJ, et al. Phenotypic variation in biotinidase deficiency. J Pediatr. 1983 Aug. 103(2):233-7. [Medline].
Zempleni J. Uptake, localization, and noncarboxylase roles of biotin. Annu Rev Nutr. 2005. 25:175-96. [Medline].