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Biotinidase deficiency

MedGen UID:
66323
Concept ID:
C0220754
Congenital Abnormality; Disease or Syndrome
Synonyms: Biotin deficiency; BTD deficiency; Late-onset biotin-responsive multiple carboxylase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Multiple carboxylase deficiency - late onset (8808004); Biotinidase deficiency (8808004); Juvenile multiple carboxylase deficiency (8808004); Late-onset multiple carboxylase deficiency (8808004); Deficiency of biotinidase (8808004)
 
Gene (location): BTD (3p25.1)
OMIM®: 253260
Orphanet: ORPHA79241

Disease characteristics

Excerpted from the GeneReview: Biotinidase Deficiency
If untreated, young children with profound biotinidase deficiency usually exhibit neurologic abnormalities including seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities (e.g., alopecia, skin rash, candidiasis). Older children and adolescents with profound biotinidase deficiency often exhibit motor limb weakness, spastic paresis, and decreased visual acuity. Once vision problems, hearing loss, and developmental delay occur, they are usually irreversible, even with biotin therapy. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress. [from GeneReviews]
Authors:
Barry Wolf   view full author information

Additional descriptions

From OMIM
Multiple carboxylase deficiency (MCD) is an autosomal recessive metabolic disorder characterized primarily by cutaneous and neurologic abnormalities. Symptoms result from the patient's inability to reutilize biotin, a necessary nutrient. Sweetman (1981) recognized that multiple carboxylase deficiency could be classified into early (see 253270) and late forms. The early form showed higher urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxypropionic acid than the late form and was associated with normal plasma biotin concentrations. Sweetman (1981) proposed a defect in holocarboxylase synthetase and intestinal biotin absorption, respectively. Some patients with biotinidase deficiency present in infancy (Baumgartner et al., 1985; Kalayci et al., 1994), and some individuals with this deficiency are asymptomatic (Wolf et al., 1997).  http://www.omim.org/entry/253260
From GHR
Biotinidase deficiency is an inherited disorder in which the body is unable to recycle the vitamin biotin. If this condition is not recognized and treated, its signs and symptoms typically appear within the first few months of life, although it can also become apparent later in childhood.Profound biotinidase deficiency, the more severe form of the condition, can cause seizures, weak muscle tone (hypotonia), breathing problems, hearing and vision loss, problems with movement and balance (ataxia), skin rashes, hair loss (alopecia), and a fungal infection called candidiasis. Affected children also have delayed development. Lifelong treatment can prevent these complications from occurring or improve them if they have already developed.Partial biotinidase deficiency is a milder form of this condition. Without treatment, affected children may experience hypotonia, skin rashes, and hair loss, but these problems may appear only during illness, infection, or other times of stress.  https://ghr.nlm.nih.gov/condition/biotinidase-deficiency

Clinical features

Conjunctivitis
MedGen UID:
1093
Concept ID:
C0009763
Disease or Syndrome
Inflammation of the conjunctiva.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Diarrhea means that you have loose, watery stools more than three times in one day. You may also have cramps, bloating, nausea and an urgent need to have a bowel movement. . Causes of diarrhea include bacteria, viruses or parasites, certain medicines, food intolerances and diseases that affect the stomach, small intestine or colon. In many cases, no cause can be found. . Although usually not harmful, diarrhea can become dangerous or signal a more serious problem. You should talk to your doctor if you have a strong pain in your abdomen or rectum, a fever, blood in your stools, severe diarrhea for more than three days or symptoms of dehydration. If your child has diarrhea, do not hesitate to call the doctor for advice. Diarrhea can be dangerous in children. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Sign or Symptom
Enlargement of the liver.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Sensorineural hearing loss
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Pathologic Function
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Tachypnea
MedGen UID:
66669
Concept ID:
C0231835
Finding
Very rapid breathing.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Hyperammonaemia
MedGen UID:
113136
Concept ID:
C0220994
Pathologic Function
Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Biotinidase deficiency in Orphanet.

Professional guidelines

PubMed

Centers for Disease Control and Prevention (CDC).
MMWR Recomm Rep 2012 Apr 6;61(RR-2):1-44. PMID: 22475884
Küry S, Ramaekers V, Bézieau S, Wolf B
Eur J Hum Genet 2012 May;20(5) Epub 2012 Feb 29 doi: 10.1038/ejhg.2012.28. PMID: 22378278Free PMC Article

External

American College of Medical Genetics ACT SHEET, Biotinidase Deficiency

American College of Medical Genetics Algorithm, Biotinidase Deficiency, 2006

Recent clinical studies

Etiology

Gannavarapu S, Prasad C, DiRaimo J, Napier M, Goobie S, Potter M, Chakraborty P, Karaceper M, Munoz T, Schulze A, MacKenzie J, Li L, Geraghty MT, Al-Dirbashi OY, Rupar CA
Mol Genet Metab 2015 Nov;116(3):146-51. Epub 2015 Aug 31 doi: 10.1016/j.ymgme.2015.08.010. PMID: 26361991
Jay AM, Conway RL, Feldman GL, Nahhas F, Spencer L, Wolf B
Genet Med 2015 Mar;17(3):205-9. Epub 2014 Aug 21 doi: 10.1038/gim.2014.104. PMID: 25144890
Gopalakrishnan V, Joshi K, Phadke S, Dabadghao P, Agarwal M, Das V, Jain S, Gambhir S, Gupta B, Pandey A, Kapoor D, Kumar M, Bhatia V
Indian Pediatr 2014 Sep;51(9):701-5. PMID: 25228601
Tiar A, Mekki A, Nagara M, Rhouma FB, Messaoud O, Halim NB, Kefi R, Hamlaoui MT, Lebied A, Abdelhak S
Gene 2014 Feb 15;536(1):193-6. Epub 2013 Feb 26 doi: 10.1016/j.gene.2013.02.011. PMID: 23481307
Afroze B, Wasay M
J Coll Physicians Surg Pak 2013 Nov;23(10):823-5. doi: 11.2013/JCPSP.823825. PMID: 24169397

Diagnosis

Wolf B
Gene 2016 Sep 10;589(2):142-50. Epub 2015 Oct 9 doi: 10.1016/j.gene.2015.10.010. PMID: 26456103
Gannavarapu S, Prasad C, DiRaimo J, Napier M, Goobie S, Potter M, Chakraborty P, Karaceper M, Munoz T, Schulze A, MacKenzie J, Li L, Geraghty MT, Al-Dirbashi OY, Rupar CA
Mol Genet Metab 2015 Nov;116(3):146-51. Epub 2015 Aug 31 doi: 10.1016/j.ymgme.2015.08.010. PMID: 26361991
Wolf B
Mol Genet Metab 2015 Nov;116(3):113-8. Epub 2015 Sep 3 doi: 10.1016/j.ymgme.2015.08.012. PMID: 26358973
Bottin L, Prud'hon S, Guey S, Giannesini C, Wolf B, Pindolia K, Stankoff B
Mult Scler 2015 Oct;21(12):1604-7. Epub 2015 Jul 22 doi: 10.1177/1352458515596457. PMID: 26203071
Li H, Spencer L, Nahhas F, Miller J, Fribley A, Feldman G, Conway R, Wolf B
Mol Genet Metab 2014 Jul;112(3):242-6. Epub 2014 Apr 16 doi: 10.1016/j.ymgme.2014.04.002. PMID: 24797656

Therapy

Wolf B
Gene 2016 Sep 10;589(2):142-50. Epub 2015 Oct 9 doi: 10.1016/j.gene.2015.10.010. PMID: 26456103
Gannavarapu S, Prasad C, DiRaimo J, Napier M, Goobie S, Potter M, Chakraborty P, Karaceper M, Munoz T, Schulze A, MacKenzie J, Li L, Geraghty MT, Al-Dirbashi OY, Rupar CA
Mol Genet Metab 2015 Nov;116(3):146-51. Epub 2015 Aug 31 doi: 10.1016/j.ymgme.2015.08.010. PMID: 26361991
Jay AM, Conway RL, Feldman GL, Nahhas F, Spencer L, Wolf B
Genet Med 2015 Mar;17(3):205-9. Epub 2014 Aug 21 doi: 10.1038/gim.2014.104. PMID: 25144890
Afroze B, Wasay M
J Coll Physicians Surg Pak 2013 Nov;23(10):823-5. doi: 11.2013/JCPSP.823825. PMID: 24169397
Kardas F, Patiroglu T, Unal E, Chiang SC, Bryceson YT, Kendirci M
Pediatr Blood Cancer 2012 Jul 15;59(1):191-3. Epub 2011 Aug 16 doi: 10.1002/pbc.23247. PMID: 22605457

Prognosis

Tonin R, Caciotti A, Funghini S, la Marca G, Pasquini E, Cayton E, Mooney SD, Guerrini R, Morrone A
Clin Chim Acta 2015 May 20;445:70-2. Epub 2015 Mar 18 doi: 10.1016/j.cca.2015.03.010. PMID: 25795614
Krishnakumar D, Maw A, Brown R, Hogg S, Calvin J, Parker AP
J Child Neurol 2014 Jan;29(1):93-5. Epub 2012 Dec 6 doi: 10.1177/0883073812467507. PMID: 23220796
Afroze B, Wasay M
J Coll Physicians Surg Pak 2013 Nov;23(10):823-5. doi: 11.2013/JCPSP.823825. PMID: 24169397
Pindolia K, Jordan M, Wolf B
Hum Mutat 2010 Sep;31(9):983-91. doi: 10.1002/humu.21303. PMID: 20556795
Ohlsson A, Guthenberg C, Holme E, von Döbeln U
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S175-80. Epub 2010 Mar 12 doi: 10.1007/s10545-010-9065-y. PMID: 20224900

Clinical prediction guides

Gannavarapu S, Prasad C, DiRaimo J, Napier M, Goobie S, Potter M, Chakraborty P, Karaceper M, Munoz T, Schulze A, MacKenzie J, Li L, Geraghty MT, Al-Dirbashi OY, Rupar CA
Mol Genet Metab 2015 Nov;116(3):146-51. Epub 2015 Aug 31 doi: 10.1016/j.ymgme.2015.08.010. PMID: 26361991
Tonin R, Caciotti A, Funghini S, la Marca G, Pasquini E, Cayton E, Mooney SD, Guerrini R, Morrone A
Clin Chim Acta 2015 May 20;445:70-2. Epub 2015 Mar 18 doi: 10.1016/j.cca.2015.03.010. PMID: 25795614
Gopalakrishnan V, Joshi K, Phadke S, Dabadghao P, Agarwal M, Das V, Jain S, Gambhir S, Gupta B, Pandey A, Kapoor D, Kumar M, Bhatia V
Indian Pediatr 2014 Sep;51(9):701-5. PMID: 25228601
Pindolia K, Jordan M, Wolf B
Hum Mutat 2010 Sep;31(9):983-91. doi: 10.1002/humu.21303. PMID: 20556795
Ohlsson A, Guthenberg C, Holme E, von Döbeln U
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S175-80. Epub 2010 Mar 12 doi: 10.1007/s10545-010-9065-y. PMID: 20224900

Recent systematic reviews

Said HM
Subcell Biochem 2012;56:1-19. doi: 10.1007/978-94-007-2199-9_1. PMID: 22116691
Ogundele MO
Arch Dis Child 2011 Sep;96(9):895-7. doi: 10.1136/archdischild-2011-300411. PMID: 21836181
Levy HL
Genet Med 2010 Dec;12(12 Suppl):S213-4. doi: 10.1097/GIM.0b013e3181fe5d77. PMID: 21150366
Cowan TM, Blitzer MG, Wolf B; Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee.
Genet Med 2010 Jul;12(7):464-70. doi: 10.1097/GIM.0b013e3181e4cc0f. PMID: 20539236
Wolf B
Mol Genet Metab 2010 May;100(1):6-13. Epub 2010 Jan 11 doi: 10.1016/j.ymgme.2010.01.003. PMID: 20129807

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