Display Settings:

Format

Send to:

Choose Destination

Biotinidase deficiency

MedGen UID:
66323
Concept ID:
C0220754
Congenital Abnormality
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
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
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]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
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 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.  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.  http://ghr.nlm.nih.gov/condition/biotinidase-deficiency

Clinical features

Organic aciduria
MedGen UID:
505042
Concept ID:
CN001803
Finding
Excretion of non-amino organic acids in urine.
Abnormal retinal pigmentation
MedGen UID:
350681
Concept ID:
C1862475
Finding
Conjunctivitis
MedGen UID:
504472
Concept ID:
CN000476
Finding
Inflammation of the conjunctiva.
Myopia
MedGen UID:
504487
Concept ID:
CN000511
Finding
An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry.
Visual loss
MedGen UID:
504502
Concept ID:
CN000537
Finding
Loss of visual acuity (implying that vision was better at a certain timepoint in life - otherwise the term reduced visual acuity should be used (or a subclass of that).
Optic atrophy
MedGen UID:
504537
Concept ID:
CN000609
Finding
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Visual field defect
MedGen UID:
504735
Concept ID:
CN001055
Finding
Inflammatory abnormality of the eye
MedGen UID:
451869
Concept ID:
CN117426
Finding
Inflammation of the eye, parts of the eye or the periorbital region.
Hearing impairment
MedGen UID:
446352
Concept ID:
CN000341
Finding
A decreased magnitude of the sensory perception of sound.
Sensorineural hearing impairment
MedGen UID:
504436
Concept ID:
CN000380
Finding
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Hypertonia
MedGen UID:
115988
Concept ID:
C0235396
Finding
Diffuse cerebellar atrophy
MedGen UID:
343184
Concept ID:
C1854699
Finding
Incoordination
MedGen UID:
351047
Concept ID:
C1864113
Finding
Seizures
MedGen UID:
409523
Concept ID:
C1959629
Finding
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Lethargy
MedGen UID:
504769
Concept ID:
CN001149
Finding
A state of disinterestedness, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Diffuse cerebral atrophy
MedGen UID:
505256
Concept ID:
CN002277
Finding
Diffuse unlocalised atrophy affecting the cerebrum.
Reduced consciousness/confusion
MedGen UID:
446594
Concept ID:
CN003871
Finding
Aplasia/Hypoplasia of the cerebellum
MedGen UID:
429099
Concept ID:
CN006441
Finding
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Diarrhea
MedGen UID:
368098
Concept ID:
C1963091
Finding
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Vomiting
MedGen UID:
776588
Concept ID:
C2712332
Finding
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
You lose up to 100 hairs from your scalp every day. That's normal, and in most people, those hairs grow back. But many men -- and some women -- lose hair as they grow older. You can also lose your hair if you have certain diseases, such as thyroid problems, diabetes, or lupus. If you take certain medicines or have chemotherapy for cancer, you may also lose your hair. Other causes are stress, a low protein diet, a family history, or poor nutrition. . Treatment for hair loss depends on the cause. In some cases, treating the underlying cause will correct the problem. Other treatments include medicines and hair restoration. .
Seborrheic dermatitis
MedGen UID:
376455
Concept ID:
C1848851
Finding
Dry skin
MedGen UID:
368099
Concept ID:
C1963094
Finding
Skin rash
MedGen UID:
504676
Concept ID:
CN000925
Finding
A red eruption of the skin.
Recurrent skin infections
MedGen UID:
504860
Concept ID:
CN001440
Finding
Infections of the skin that happen multiple times.
Skin ulcer
MedGen UID:
506561
Concept ID:
CN117783
Finding
A discontinuity of the skin exhibiting complete loss of the epidermis and often portions of the dermis and even subcutaneous fat.
Hyperammonemia
MedGen UID:
505040
Concept ID:
CN001799
Finding
An increased concentration of ammonia in the blood.
Organic aciduria
MedGen UID:
505042
Concept ID:
CN001803
Finding
Excretion of non-amino organic acids in urine.
Metabolic ketoacidosis
MedGen UID:
505875
Concept ID:
CN005269
Finding
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Pathologic Function
A disorder characterized by cessation of breathing.
Tachypnea
MedGen UID:
66669
Concept ID:
C0231835
Sign or Symptom
Increased RESPIRATORY RATE.
Respiratory insufficiency
MedGen UID:
155440
Concept ID:
C0748358
Finding
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Sign or Symptom
A diminution of the skeletal muscle tone marked by a diminished resistance to passive stretching.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)
Hypertonia
MedGen UID:
115988
Concept ID:
C0235396
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews

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. [Epub ahead of print] 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

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. [Epub ahead of print] PMID: 23481307
Afroze B, Wasay M
J Coll Physicians Surg Pak 2013 Nov;23(10):823-5. doi: 11.2013/JCPSP.823825. PMID: 24169397
Venkataraman V, Balaji P, Panigrahi D, Jamal R
Neurol India 2013 Jul-Aug;61(4):411-3. doi: 10.4103/0028-3886.117614. PMID: 24005734
Cowan TM, Kazerouni NN, Dharajiya N, Lorey F, Roberson M, Hodgkinson C, Schrijver I
Mol Genet Metab 2012 Aug;106(4):485-7. Epub 2012 May 30 doi: 10.1016/j.ymgme.2012.05.017. [Epub ahead of print] PMID: 22698809

Diagnosis

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
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. [Epub ahead of print] PMID: 24797656
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. [Epub ahead of print] PMID: 23481307
Afroze B, Wasay M
J Coll Physicians Surg Pak 2013 Nov;23(10):823-5. doi: 11.2013/JCPSP.823825. PMID: 24169397
Graham C, Sista RS, Kleinert J, Wu N, Eckhardt A, Bali D, Millington DS, Pamula VK
Clin Biochem 2013 Dec;46(18):1889-91. Epub 2013 Sep 11 doi: 10.1016/j.clinbiochem.2013.09.003. [Epub ahead of print] PMID: 24036022Free PMC Article

Therapy

Borsatto T, Sperb-Ludwig F, Pinto LL, Luca GR, Carvalho FL, Souza CF, Medeiros PF, Lourenço CM, Lo Filho R, Neto EC, Bernardi P, Leistner-Segal S, Schwartz IV
BMC Med Genet 2014 Sep 1;15:96. doi: 10.1186/s12881-014-0096-3. [Epub ahead of print] PMID: 25174816Free PMC Article
Afroze B, Wasay M
J Coll Physicians Surg Pak 2013 Nov;23(10):823-5. doi: 11.2013/JCPSP.823825. PMID: 24169397
Thodi G, Schulpis KH, Molou E, Georgiou V, Loukas YL, Dotsikas Y, Papadopoulos K, Biti S
Gene 2013 Jul 25;524(2):361-2. Epub 2013 Apr 30 doi: 10.1016/j.gene.2013.04.059. [Epub ahead of print] PMID: 23644139
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. [Epub ahead of print] PMID: 22605457
Wolf B
Genet Med 2012 Jun;14(6):565-75. Epub 2012 Jan 5 doi: 10.1038/gim.2011.6. [Epub ahead of print] PMID: 22241090

Prognosis

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. [Epub ahead of print] PMID: 23220796
Afroze B, Wasay M
J Coll Physicians Surg Pak 2013 Nov;23(10):823-5. doi: 11.2013/JCPSP.823825. PMID: 24169397
Jagadeesh S, Suresh B, Seshadri S, Suzuki Y
Natl Med J India 2013 Jan-Feb;26(1):29-30. PMID: 24066991
Venkataraman V, Balaji P, Panigrahi D, Jamal R
Neurol India 2013 Jul-Aug;61(4):411-3. doi: 10.4103/0028-3886.117614. PMID: 24005734
Thodi G, Schulpis KH, Molou E, Georgiou V, Loukas YL, Dotsikas Y, Papadopoulos K, Biti S
Gene 2013 Jul 25;524(2):361-2. Epub 2013 Apr 30 doi: 10.1016/j.gene.2013.04.059. [Epub ahead of print] PMID: 23644139

Clinical prediction guides

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
Borsatto T, Sperb-Ludwig F, Pinto LL, Luca GR, Carvalho FL, Souza CF, Medeiros PF, Lourenço CM, Lo Filho R, Neto EC, Bernardi P, Leistner-Segal S, Schwartz IV
BMC Med Genet 2014 Sep 1;15:96. doi: 10.1186/s12881-014-0096-3. [Epub ahead of print] PMID: 25174816Free PMC Article
Hernández-Vázquez A, Wolf B, Pindolia K, Ortega-Cuellar D, Hernández-González R, Heredia-Antúnez A, Ibarra-González I, Velázquez-Arellano A
Mol Genet Metab 2013 Nov;110(3):248-54. Epub 2013 Sep 8 doi: 10.1016/j.ymgme.2013.08.018. [Epub ahead of print] PMID: 24075304
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. [Epub ahead of print] 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. [Epub ahead of print] PMID: 20129807

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...