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Biotinidase deficiency

MedGen UID:
66323
Concept ID:
C0220754
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); 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.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
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 loss
MedGen UID:
784038
Concept ID:
C3665386
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).
Organic aciduria
MedGen UID:
66037
Concept ID:
C0241775
Finding
Excretion of non-amino organic acids in urine.
Conjunctivitis
MedGen UID:
1093
Concept ID:
C0009763
Disease or Syndrome
Inflammation of the conjunctiva.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
What is diarrhea? Diarrhea is loose, watery stools (bowel movements). You have diarrhea if you have loose stools three or more times in one day. Acute diarrhea is diarrhea that lasts a short time. It is a common problem. It usually lasts about one or two days, but it may last longer. Then it goes away on its own. Diarrhea lasting more than a few days may be a sign of a more serious problem. Chronic diarrhea -- diarrhea that lasts at least four weeks -- can be a symptom of a chronic disease. Chronic diarrhea symptoms may be continual, or they may come and go. Who gets diarrhea? People of all ages can get diarrhea. On average, adults In the United States have acute diarrhea once a year. Young children have it an average of twice a year. People who visit developing countries are at risk for traveler's diarrhea. It is caused by consuming contaminated food or water. What causes diarrhea? The most common causes of diarrhea include. -Bacteria from contaminated food or water. -Viruses such as the flu, norovirus, or rotavirus . Rotavirus is the most common cause of acute diarrhea in children. -Parasites, which are tiny organisms found in contaminated food or water. -Medicines such as antibiotics, cancer drugs, and antacids that contain magnesium. -Food intolerances and sensitivities, which are problems digesting certain ingredients or foods. An example is lactose intolerance. -Diseases that affect the stomach, small intestine, or colon, such as Crohn's disease. -Problems with how the colon functions, such as irritable bowel syndrome. Some people also get diarrhea after stomach surgery, because sometimes the surgeries can cause food to move through your digestive system more quickly. Sometimes no cause can be found. If your diarrhea goes away within a few days, finding the cause is usually not necessary. What other symptoms might I have with diarrhea? Other possible symptoms of diarrhea include. -Cramps or pain in the abdomen. -An urgent need to use the bathroom. -Loss of bowel control. If a virus or bacteria is the cause of your diarrhea, you may also have a fever, chills, and bloody stools. Diarrhea can cause dehydration, which means that your body does not have enough fluid to work properly. Dehydration can be serious, especially for children, older adults, and people with weakened immune systems. When should I see a doctor for diarrhea? Although it is usually not harmful, diarrhea can become dangerous or signal a more serious problem. Contact your health care provider if you have. -Signs of dehydration. -Diarrhea for more than 2 days, if you are an adult. For children, contact the provider if it lasts more than 24 hours. -Severe pain in your abdomen or rectum (for adults). -A fever of 102 degrees or higher. -Stools containing blood or pus. -Stools that are black and tarry. If children have diarrhea, parents or caregivers should not hesitate to call a health care provider. Diarrhea can be especially dangerous in newborns and infants. How is the cause of diarrhea diagnosed? To find the cause of diarrhea, your health care provider may. -Do a physical exam. -Ask about any medicines you are taking. -Test your stool or blood to look for bacteria, parasites, or other signs of disease or infection. -Ask you to stop eating certain foods to see whether your diarrhea goes away. If you have chronic diarrhea, your health care provider may perform other tests to look for signs of disease. What are the treatments for diarrhea? Diarrhea is treated by replacing lost fluids and electrolytes to prevent dehydration. Depending on the cause of the problem, you may need medicines to stop the diarrhea or treat an infection. Adults with diarrhea should drink water, fruit juices, sports drinks, sodas without caffeine, and salty broths. As your symptoms improve, you can eat soft, bland food. Children with diarrhea should be given oral rehydration solutions to replace lost fluids and electrolytes. Can diarrhea be prevented? Two types of diarrhea can be prevented - rotavirus diarrhea and traveler's diarrhea. There are vaccines for rotavirus. They are given to babies in two or three doses. You can help prevent traveler's diarrhea by being careful about what you eat and drink when you are in developing countries:. -Use only bottled or purified water for drinking, making ice cubes, and brushing your teeth. -If you do use tap water, boil it or use iodine tablets. -Make sure that the cooked food you eat is fully cooked and served hot. -Avoid unwashed or unpeeled raw fruits and vegetables. NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
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.
Ataxia
MedGen UID:
849
Concept ID:
C0007758
Sign or Symptom
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).
Seizure Disorders
MedGen UID:
4506
Concept ID:
C0014544
Disease or Syndrome
Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. People may have strange sensations and emotions or behave strangely. They may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, and abnormal brain development. In many cases, the cause is unknown. Doctors use brain scans and other tests to diagnose epilepsy. It is important to start treatment right away. There is no cure for epilepsy, but medicines can control seizures for most people. When medicines are not working well, surgery or implanted devices such as vagus nerve stimulators may help. Special diets can help some children with epilepsy. NIH: National Institute of Neurological Disorders and Stroke.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of disinterestedness, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
Diffuse cerebral atrophy
MedGen UID:
108958
Concept ID:
C0598275
Finding
Diffuse unlocalised atrophy affecting the cerebrum.
Diffuse cerebellar atrophy
MedGen UID:
343184
Concept ID:
C1854699
Finding
Diffuse unlocalised atrophy affecting the cerebellum.
Cognitive delay
MedGen UID:
351243
Concept ID:
C1864897
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.
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.
Organic aciduria
MedGen UID:
66037
Concept ID:
C0241775
Finding
Excretion of non-amino organic acids in urine.
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.
Conjunctivitis
MedGen UID:
1093
Concept ID:
C0009763
Disease or Syndrome
Inflammation of the conjunctiva.
Skin rash
MedGen UID:
8732
Concept ID:
C0015230
Finding
A rash is an area of irritated or swollen skin. Many rashes are itchy, red, painful, and irritated. Some rashes can also lead to blisters or patches of raw skin. Rashes are a symptom of many different medical problems. Other causes include irritating substances and allergies. Certain genes can make people more likely to get rashes. Contact dermatitis is a common type of rash. It causes redness, itching, and sometimes small bumps. You get the rash where you have touched an irritant, such as a chemical, or something you are allergic to, like poison ivy. Some rashes develop right away. Others form over several days. Although most rashes clear up fairly quickly, others are long-lasting and need long-term treatment. Because rashes can be caused by many different things, it's important to figure out what kind you have before you treat it. If it is a bad rash, if it does not go away, or if you have other symptoms, you should see your health care provider. Treatments may include moisturizers, lotions, baths, cortisone creams that relieve swelling, and antihistamines, which relieve itching.
Seborrheic dermatitis
MedGen UID:
19912
Concept ID:
C0036508
Disease or Syndrome
A chronic inflammatory disease of the skin with unknown etiology. It is characterized by moderate ERYTHEMA, dry, moist, or greasy (SEBACEOUS GLAND) scaling and yellow crusted patches on various areas, especially the scalp, that exfoliate as dandruff. Seborrheic dermatitis is common in children and adolescents with HIV INFECTIONS.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Finding
Infections of the skin that happen multiple times.
Hyperammonaemia
MedGen UID:
113136
Concept ID:
C0220994
Disease or Syndrome
Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.
Organic aciduria
MedGen UID:
66037
Concept ID:
C0241775
Finding
Excretion of non-amino organic acids in urine.
Metabolic ketoacidosis
MedGen UID:
381478
Concept ID:
C1854704
Pathologic Function
Conjunctivitis
MedGen UID:
1093
Concept ID:
C0009763
Disease or Syndrome
Inflammation of the conjunctiva.
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. .
Skin rash
MedGen UID:
8732
Concept ID:
C0015230
Finding
A rash is an area of irritated or swollen skin. Many rashes are itchy, red, painful, and irritated. Some rashes can also lead to blisters or patches of raw skin. Rashes are a symptom of many different medical problems. Other causes include irritating substances and allergies. Certain genes can make people more likely to get rashes. Contact dermatitis is a common type of rash. It causes redness, itching, and sometimes small bumps. You get the rash where you have touched an irritant, such as a chemical, or something you are allergic to, like poison ivy. Some rashes develop right away. Others form over several days. Although most rashes clear up fairly quickly, others are long-lasting and need long-term treatment. Because rashes can be caused by many different things, it's important to figure out what kind you have before you treat it. If it is a bad rash, if it does not go away, or if you have other symptoms, you should see your health care provider. Treatments may include moisturizers, lotions, baths, cortisone creams that relieve swelling, and antihistamines, which relieve itching.
Seborrheic dermatitis
MedGen UID:
19912
Concept ID:
C0036508
Disease or Syndrome
A chronic inflammatory disease of the skin with unknown etiology. It is characterized by moderate ERYTHEMA, dry, moist, or greasy (SEBACEOUS GLAND) scaling and yellow crusted patches on various areas, especially the scalp, that exfoliate as dandruff. Seborrheic dermatitis is common in children and adolescents with HIV INFECTIONS.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Finding
Infections of the skin that happen multiple times.

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
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
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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