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Biotinidase Deficiency

Pathophysiology description (concise knowledge-base paragraph)

2026-02-23
Falcon MONDO:0009665 Model: Edison Scientific Literature 24 citations

Pathophysiology description (concise knowledge-base paragraph) BTD deficiency is an autosomal recessive disorder caused by loss of biotinidase activity, leading to failure of biotin recycling from biocytin/biotinyl-peptides and subsequent depletion of free biotin. The resulting functional deficiency of biotin-dependent carboxylases (including pyruvate carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase) causes metabolic acidosis/lactic acidosis, hyperammonemia, and organic aciduria with characteristic elevations such as C3 and C5‑OH acylcarnitines and urinary 3-hydroxyisovalerate/methylcitrate. CNS-predominant injury includes white matter/myelination abnormalities and involvement of specific neuroanatomical structures (e.g., fornices/brainstem/optic pathways/spinal cord), producing seizures, developmental delay, hypotonia, and potentially irreversible hearing/vision loss when untreated or treated late. Early newborn screening and prompt, lifelong oral biotin prevent disease manifestation in most cases. (devanapalli2024biotinidasedeficiencya pages 1-3, karachaliou2024biotinhomeostasisand pages 5-7, devanapalli2024biotinidasedeficiencya pages 3-5, biswas2023neuroimagingfeaturesof pages 3-4)

Gene/protein annotations • BTD (biotinidase) — causal gene; biallelic pathogenic variants reduce enzyme activity; severity correlates with residual activity categories (profound vs partial). (devanapalli2024biotinidasedeficiencya pages 1-3, karachaliou2024biotinhomeostasisand pages 5-7)

Representative genotype–phenotype notes (recent cohort) • Turin NBS cohort: D444H associated mostly with partial BTD; Q456H present in many profound cases; complex allele A171T/D444H can yield partial or profound depending on trans allele. (bracci2024biotinidasedeficiencyoutcomes pages 10-12)

GO biological process candidates (mechanism-linked) • Biotin metabolic process / biotin recycling (biotin cycle). (karachaliou2024biotinhomeostasisand pages 4-5) • Protein biotinylation / activation of carboxylases (HLCS-mediated). (karachaliou2024biotinhomeostasisand pages 4-5) • Gluconeogenesis (PC-linked) and propionate metabolism (PCC-linked). (karachaliou2024biotinhomeostasisand pages 5-7)

Cellular component candidates • Cytosol and mitochondrion (intermediary metabolism/organic acidemia-like biochemical phenotype implicates mitochondrial/cytosolic metabolic pathways). (devanapalli2024biotinidasedeficiencya pages 1-3, karachaliou2024biotinhomeostasisand pages 5-7)

Phenotype associations (HP term examples; evidence-supported) • Seizures; hypotonia; developmental delay; ataxia; hearing loss; optic atrophy/vision loss; skin rash; alopecia; metabolic acidosis; hyperammonemia; organic aciduria. (devanapalli2024biotinidasedeficiencya pages 1-3, devanapalli2024biotinidasedeficiencya pages 3-5, motta2024organicacidemiasclinical pages 9-10, biswas2023neuroimagingfeaturesof pages 3-4)

Cell type involvement (CL examples) • Cerebellar Purkinje cells (localization evidence). (devanapalli2024biotinidasedeficiencya pages 3-5) • Auditory brainstem nuclei (localization evidence). (devanapalli2024biotinidasedeficiencya pages 3-5)

Anatomical locations (UBERON examples) • Brain white matter/cerebellum/red nucleus/brainstem/optic pathway/spinal cord; skin. (devanapalli2024biotinidasedeficiencya pages 3-5, biswas2023neuroimagingfeaturesof pages 3-4)

Chemical entities (CHEBI examples) • Biotin; biocytin; lactate; propionylcarnitine (C3); 3-hydroxyisovaleryl-carnitine (C5‑OH); 3-hydroxyisovaleric acid; methylcitrate. (devanapalli2024biotinidasedeficiencya pages 1-3, karachaliou2024biotinhomeostasisand pages 5-7, liu2023delayedbiotintherapy pages 2-3)

13) Evidence items (PMID preference; availability note)

The retrieved full-text snippets in this run did not include PMIDs inline for the core 2024 IJMS review or the 2024 Brain & Development Case Reports article; however, peer-reviewed sources with DOI/URL and publication dates are provided below and are suitable for citation.

Key recent sources (URLs and publication dates) • Karachaliou C‑E, Livaniou E. “Biotin Homeostasis and Human Disorders: Recent Findings and Perspectives.” International Journal of Molecular Sciences. June 2024. https://doi.org/10.3390/ijms25126578 (karachaliou2024biotinhomeostasisand pages 5-7) • Devanapalli B, et al. “Biotinidase deficiency: A treatable neurometabolic disorder.” Brain and Development Case Reports. June 2024. https://doi.org/10.1016/j.bdcasr.2024.100021 (devanapalli2024biotinidasedeficiencya pages 1-3, devanapalli2024biotinidasedeficiencya pages 3-5, devanapalli2024biotinidasedeficiencya pages 5-7) • Biswas A, et al. “Neuroimaging Features of Biotinidase Deficiency.” American Journal of Neuroradiology. February 2023. https://doi.org/10.3174/ajnr.a7781 (biswas2023neuroimagingfeaturesof pages 1-3, biswas2023neuroimagingfeaturesof pages 3-4) • Liu S, et al. “Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency…” International Journal of Molecular Sciences. June 2023. https://doi.org/10.3390/ijms241210239 (liu2023delayedbiotintherapy pages 1-2, liu2023delayedbiotintherapy pages 2-3)

Limitations This tool run retrieved strong mechanistic and real-world screening/treatment evidence but did not successfully obtain the full text of one highly relevant 2023 historical synthesis (“Biotinidase deficiency: what have we learned in forty years?”, doi:10.1016/j.ymgme.2023.107560) and therefore cannot directly quote/cite it here. (No citeable context available in this run.)

References

  1. (bracci2024biotinidasedeficiencyoutcomes pages 10-12): B Bracci, D Mala, E Pavanello, and P Sauro. Biotinidase deficiency: outcomes of 37 years-experience of newborn screening in turin, italy. Unknown journal, 2024.

  2. (devanapalli2024biotinidasedeficiencya pages 1-3): Beena Devanapalli, Rachel Sze Hui Wong, Natalie Lim, P Ian Andrews, Keshini Vijayan, Won-Tae Kim, Tiffany Wotton, Esther Tantsis, Enzo Ranieri, Adviye Ayper Tolun, and Shanti Balasubramaniam. Biotinidase deficiency: a treatable neurometabolic disorder. Brain and Development Case Reports, 2:100021, Jun 2024. URL: https://doi.org/10.1016/j.bdcasr.2024.100021, doi:10.1016/j.bdcasr.2024.100021. This article has 5 citations.

  3. (karachaliou2024biotinhomeostasisand pages 5-7): Chrysoula-Evangelia Karachaliou and Evangelia Livaniou. Biotin homeostasis and human disorders: recent findings and perspectives. International Journal of Molecular Sciences, 25:6578, Jun 2024. URL: https://doi.org/10.3390/ijms25126578, doi:10.3390/ijms25126578. This article has 45 citations.

  4. (motta2024organicacidemiasclinical pages 9-10): Mario Motta, Mohammad Mozibur Rahman, Gayatri Athalye-Jape, and Monika Kaushal. Organic acidemias: clinical presentation in neonates. Newborn, 2:263-278, Jan 2024. URL: https://doi.org/10.5005/jp-journals-11002-0080, doi:10.5005/jp-journals-11002-0080. This article has 3 citations.

  5. (karachaliou2024biotinhomeostasisand pages 4-5): Chrysoula-Evangelia Karachaliou and Evangelia Livaniou. Biotin homeostasis and human disorders: recent findings and perspectives. International Journal of Molecular Sciences, 25:6578, Jun 2024. URL: https://doi.org/10.3390/ijms25126578, doi:10.3390/ijms25126578. This article has 45 citations.

  6. (karachaliou2024biotinhomeostasisand media 2c556c74): Chrysoula-Evangelia Karachaliou and Evangelia Livaniou. Biotin homeostasis and human disorders: recent findings and perspectives. International Journal of Molecular Sciences, 25:6578, Jun 2024. URL: https://doi.org/10.3390/ijms25126578, doi:10.3390/ijms25126578. This article has 45 citations.

  7. (karachaliou2024biotinhomeostasisand media c7e991bf): Chrysoula-Evangelia Karachaliou and Evangelia Livaniou. Biotin homeostasis and human disorders: recent findings and perspectives. International Journal of Molecular Sciences, 25:6578, Jun 2024. URL: https://doi.org/10.3390/ijms25126578, doi:10.3390/ijms25126578. This article has 45 citations.

  8. (karachaliou2024biotinhomeostasisand media c9e70a46): Chrysoula-Evangelia Karachaliou and Evangelia Livaniou. Biotin homeostasis and human disorders: recent findings and perspectives. International Journal of Molecular Sciences, 25:6578, Jun 2024. URL: https://doi.org/10.3390/ijms25126578, doi:10.3390/ijms25126578. This article has 45 citations.

  9. (devanapalli2024biotinidasedeficiencya pages 3-5): Beena Devanapalli, Rachel Sze Hui Wong, Natalie Lim, P Ian Andrews, Keshini Vijayan, Won-Tae Kim, Tiffany Wotton, Esther Tantsis, Enzo Ranieri, Adviye Ayper Tolun, and Shanti Balasubramaniam. Biotinidase deficiency: a treatable neurometabolic disorder. Brain and Development Case Reports, 2:100021, Jun 2024. URL: https://doi.org/10.1016/j.bdcasr.2024.100021, doi:10.1016/j.bdcasr.2024.100021. This article has 5 citations.

  10. (biswas2023neuroimagingfeaturesof pages 1-3): A. Biswas, C. McNamara, V. Gowda, F. Gala, S. Sudhakar, M. S. J. Sidpra, P. Vari, S. Striano, M. Blaser, S. Severino, K. Batzios, Mankad, Istituto di Ricovero e Cura, and Carattere Scientifico. Neuroimaging features of biotinidase deficiency. American Journal of Neuroradiology, 44:328-333, Feb 2023. URL: https://doi.org/10.3174/ajnr.a7781, doi:10.3174/ajnr.a7781. This article has 17 citations and is from a peer-reviewed journal.

  11. (biswas2023neuroimagingfeaturesof pages 3-4): A. Biswas, C. McNamara, V. Gowda, F. Gala, S. Sudhakar, M. S. J. Sidpra, P. Vari, S. Striano, M. Blaser, S. Severino, K. Batzios, Mankad, Istituto di Ricovero e Cura, and Carattere Scientifico. Neuroimaging features of biotinidase deficiency. American Journal of Neuroradiology, 44:328-333, Feb 2023. URL: https://doi.org/10.3174/ajnr.a7781, doi:10.3174/ajnr.a7781. This article has 17 citations and is from a peer-reviewed journal.

  12. (alharbi2023overviewonpathophysiology pages 2-4): Faisal Mohammed Alharbi, Ahmad Sughaier Albalawi, Fawaz Khalifah Alanazi, Turki Saleh Alshehri, Badriah Abdulrahman Alsabah, and Alaa Saud Alyasi. Overview on pathophysiology, diagnosis, and management of biotinidase deficiency in pediatrics. Archives of Pharmacy Practice, 14:99-105, Jan 2023. URL: https://doi.org/10.51847/8hpvomjrdl, doi:10.51847/8hpvomjrdl. This article has 1 citations.

  13. (liu2023delayedbiotintherapy pages 6-7): Shu Liu, Ye Zhang, Zhi Deng, Hui He, Xianhua Zheng, Qingshan Hong, and Xianqiong Luo. Delayed biotin therapy in a child with atypical profound biotinidase deficiency: late arrival of the truth and a lesson worth thinking. International Journal of Molecular Sciences, 24:10239, Jun 2023. URL: https://doi.org/10.3390/ijms241210239, doi:10.3390/ijms241210239. This article has 4 citations.

  14. (liu2023delayedbiotintherapy pages 1-2): Shu Liu, Ye Zhang, Zhi Deng, Hui He, Xianhua Zheng, Qingshan Hong, and Xianqiong Luo. Delayed biotin therapy in a child with atypical profound biotinidase deficiency: late arrival of the truth and a lesson worth thinking. International Journal of Molecular Sciences, 24:10239, Jun 2023. URL: https://doi.org/10.3390/ijms241210239, doi:10.3390/ijms241210239. This article has 4 citations.

  15. (liu2023delayedbiotintherapy pages 2-3): Shu Liu, Ye Zhang, Zhi Deng, Hui He, Xianhua Zheng, Qingshan Hong, and Xianqiong Luo. Delayed biotin therapy in a child with atypical profound biotinidase deficiency: late arrival of the truth and a lesson worth thinking. International Journal of Molecular Sciences, 24:10239, Jun 2023. URL: https://doi.org/10.3390/ijms241210239, doi:10.3390/ijms241210239. This article has 4 citations.

  16. (liu2023delayedbiotintherapy pages 3-6): Shu Liu, Ye Zhang, Zhi Deng, Hui He, Xianhua Zheng, Qingshan Hong, and Xianqiong Luo. Delayed biotin therapy in a child with atypical profound biotinidase deficiency: late arrival of the truth and a lesson worth thinking. International Journal of Molecular Sciences, 24:10239, Jun 2023. URL: https://doi.org/10.3390/ijms241210239, doi:10.3390/ijms241210239. This article has 4 citations.

  17. (devanapalli2024biotinidasedeficiencya pages 5-7): Beena Devanapalli, Rachel Sze Hui Wong, Natalie Lim, P Ian Andrews, Keshini Vijayan, Won-Tae Kim, Tiffany Wotton, Esther Tantsis, Enzo Ranieri, Adviye Ayper Tolun, and Shanti Balasubramaniam. Biotinidase deficiency: a treatable neurometabolic disorder. Brain and Development Case Reports, 2:100021, Jun 2024. URL: https://doi.org/10.1016/j.bdcasr.2024.100021, doi:10.1016/j.bdcasr.2024.100021. This article has 5 citations.