2 dez. Introdução: a deficiência de biotinidase é uma doença metabólica hereditária, com herança autossômica recessiva, causada por mutações no. Qué es la deficiencia de biotinidasa? ¿Qué es la deficiencia de biotinidasa? menu button. previous button. next button. Turn on your speakers. menu button. previous button. next button.
|Published (Last):||2 September 2018|
|PDF File Size:||11.84 Mb|
|ePub File Size:||14.33 Mb|
|Price:||Free* [*Free Regsitration Required]|
University of Washington, Seattle; March 24, ; Last Update: 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. 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. All symptomatic children with profound biotinidase deficiency improve when treated with mg of oral biotin per day.
All individuals with profound biotinidase deficiency, even those who have some residual enzymatic activity, should have lifelong treatment with biotin. Children with vision problems may benefit from vision aids; those with hearing loss will usually benefit from hearing aids or cochlear implants, and those with developmental deficits from appropriate interventions.
Prevention of primary manifestations: Children with biotinidase deficiency identified by newborn screening should remain asymptomatic if biotin therapy is instituted early and continuously lifelong. Annual vision and hearing evaluation, physical examination, and periodic assessment by a metabolic specialist. Raw eggs because they contain avidin, an egg-white protein that binds biotin and decreases the bioavailability of the vitamin. Evaluation of relatives at risk: Testing of asymptomatic sibs of a proband ensures that biotin therapy for affected sibs can be ce in a timely manner.
Biotinidase deficiency is inherited in an autosomal recessive manner. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are options if the pathogenic variants in the family are known. Clinical issues and frequently asked questions regarding biotinidase deficiency have been addressed in a review [ Wolf ]. Biotinidase deficiency should be suspected in infants with biotinifasa newborn screening results, untreated individuals with clinical findings, and persons with suggestive preliminary laboratory findings [ Wolf ]:.
Newborn screening utilizes a small biotiniidasa of blood obtained from a heel prick for a colorimetric test for biotinidase activity:. Children or adults with untreated profound biotinidase deficiency usually exhibit one or more of the following non-specific features which are also observed in many other inherited metabolic disorders:. Older children and adolescents may exhibit limb weakness, paresis, and scotomata. Some have exhibited findings suggestive of a myelopathy and have been initially incorrectly diagnosed and treated as having another disorder before biotinidase deficiency is correctly diagnosed [ Wolf ].
Children or adults with untreated partial biotinidase deficiency may dericiencia any of the above signs and symptoms, but the manifestations are mild and occur only when the person is stressed, such as with a prolonged infection.
The diagnosis of biotinidase deficiency is established in a proband whose newborn screening or biochemical findings indicate multiple carboxylase deficiency based on EITHER of the following:.
Biotinidase enzyme activity in serum. The working group of the American College of Medical Genetics Laboratory Quality Assurance Committee has established technical standards and guidelines for the diagnosis of biotinidase deficiency [ Cowan et al ] full text. Molecular genetic testing is performed by single- gene testing. View in own window. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.
Sequence analysis detects variants that are benign, likely benign, of uncertain significancelikely pathogenic, or pathogenic. For issues to consider in interpretation of sequence analysis results, click here. Almost ve individuals with partial biotinidase deficiency have the pathogenic variant p.
AspHis in one allele of BTD in combination biotinidxsa a pathogenic variant for profound deficiency in the other biotjnidasa [ Swango et al ]. Methods that may be used include: Two large BTD deletions have been reported in affected individuals [ Senanayake et alWolf ]. Individuals with ee deficiency who are diagnosed before they have developed symptoms e. Neurologic problems occur only in those individuals with biotinidase deficiency who have recurrent symptoms and metabolic compromise prior to biotin treatment.
Some children with biotinidase deficiency manifest only a single finding, whereas others exhibit multiple neurologic and cutaneous findings. The most common neurologic features in individuals with untreated, profound biotinidase deficiency are seizures and hypotonia [ Wolf et al aWolf et al bWastell et alWolfWolf ].
The seizures are usually myoclonic but may be grand mal and focal; some children have infantile spasms [ Salbert et al b ].
Some untreated children have exhibited spinal cord involvement characterized by progressive spastic paresis and myelopathy [ Chedrawi et al ]. Older affected children often have ataxia and developmental delay.
These findings may improve or become normal after biotin treatment. Sensorineural hearing loss and eye problems e. Cutaneous biotiindasa include skin rash, alopecia, and recurrent viral or fungal infections caused by immunologic dysfunction.
One death initially thought to be caused by sudden infant death syndrome was subsequently attributed to biotinidase deficiency [ Burton et al ]. A number of children with profound biotinidase deficiency were asymptomatic until adolescence, when they developed sudden loss of vision with progressive optic neuropathy and spastic paraparesis [ Ramaekers et alLott et alRamaekers et al ].
After several months defficiencia biotin therapy, the eye findings resolved and the spastic paraparesis improved. In other individuals with enzyme deficiency, paresis and eye problems have occurred during early adolescence [ Tokatli et alWolf et alWolf ].
One child with partial biotinidase deficiency who was not treated with biotin exhibited hypotonia, skin rash, and hair loss during an episode of gastroenteritis at approximately age six months. When treated with biotin, the symptoms resolved. Deletions, insertions, or nonsense variants usually result in complete absence of biotinidase enzyme activity, whereas missense variants may or may not result in complete loss of biotinidase enzyme activity.
Those with absence of all biotinidase enzyme activity are likely to be at increased risk for earlier onset of symptoms. Although genotype-phenotype correlations are ds well established, in one study, children with symptoms of profound biotinidase deficiency with null variants were more likely to develop hearing loss than those with missense variants, even if not treated for a period of time [ Sivri et al ].
Certain genotypes correlate with complete biotinidase deficiency and others with partial biotinidase deficiency. Almost all children with profound biotinidase deficiency become symptomatic or are at risk of becoming symptomatic if not treated.
DeCS Server – List Exact Term
Several reports describe adults with profound bjotinidasa deficiency who have offspring who also have profound biotinidase deficiency identified by newborn screeningbut who have never had symptoms [ Wolf et alBaykal et al ]. In addition, several enzyme-deficient sibs of symptomatic children have apparently never exhibited symptoms.
It is possible that these individuals would biotjnidasa symptomatic if stressed, such as with a prolonged infection. Individuals with partial biotinidase deficiency were previously described as having late-onset or juvenile multiple or combined carboxylase deficiency.
Biotinidase deficiency should not be confused with holocarboxylase synthetase deficiency see Differential Diagnosispreviously refered to as early-onset or infantile multiple or combined carboxylase deficiency. Based on the results of worldwide screening of biotinidase deficiency [ Wolf ], the incidence of the disorder is:. The incidence of biotinidase deficiency is generally higher in populations with a high rate of consanguinity e.
The incidence appears to be increased in the Hispanic population [ Cowan et al ] and it may be lower in deficlencia African American population.
No biotiidasa other than those discussed in this GeneReview are known to be associated with pathogenic variants in BTD. Clinical features including vomiting, hypotonia, and seizures accompanied by metabolic ketolactic acidosis or mild hyperammonemia are often observed in inherited metabolic diseases.
Individuals with biotinidase deficiency may exhibit clinical features that are misdiagnosed as other disorders e. Other symptoms that are more characteristic of biotinidase deficiency e. The biotin cycle Free biotin enters the cycle from dietary sources or from the cleavage of biocytin or biotinyl-peptides by the action of bootinidasa. The free biotin is then covalently attached to the various apocarboxylases, propionyl-CoA carboxylase more Biotin deficiency can usually be diagnosed by dietary history.
Individuals with biotin deficiency may have a diet containing raw eggs or protracted parenteral hyperalimentation without biotin supplementation. Low-serum biotin concentrations are useful in differentiating biotin and biotinidase deficiencies from holocarboxylase synthetase deficiency; however, it is important to know the method used for determining the biotin concentration as only biotihidasa that distinguish biotin from biocytin or bound biotin yield reliable estimates of free biotin concentrations.
Urinary organic acid analysis is useful for differentiating isolated carboxylase deficiencies from the multiple carboxylase deficiencies that occur in biotinidase deficiency and holocarboxylase synthetase deficiency:.
The multiple carboxylase deficiencies are biotin responsive, whereas the isolated carboxylase deficiencies are not. A trial of biotin can be useful for discriminating between the disorders. Isolated carboxylase deficiency can be diagnosed by demonstrating deficient enzyme activity of one of the three mitochondrial carboxylases in peripheral blood leukocytes prior to biotin therapy or in cultured fibroblasts grown in low biotin-containing medium, and normal activity of the other two carboxylases.
Biotinidase deficiency – Wikipedia
Holocarboxylase synthetase deficiency OMIM Both biotinidase deficiency and holocarboxylase synthetase deficiency are characterized by deficient activities of the three mitochondrial carboxylases in peripheral blood leukocytes prior to biotin treatment. In both disorders, these activities increase to near-normal or normal after biotin treatment. The symptoms of biotinidase deficiency and holocarboxylase synthetase deficiency are similar, and clinical differentiation is often difficult.
The age of onset of symptoms may be useful for distinguishing between holocarboxylase synthetase deficiency and biotinidase deficiency. Holocarboxylase synthetase deficiency deficidncia presents with symptoms before age three months, whereas biotinidase deficiency usually presents after age three months; however, there are exceptions for both disorders. Organic acid abnormalities in biotinidase deficiency and holocarboxylase synthetase deficiency are similar and may be bitoinidasa as consistent with multiple carboxylase deficiency.
However, the tandem mass spectroscopic methodology that is being incorporated into many newborn screening programs should identify metabolites that are consistent with multiple carboxylase deficiency. Because most children with holocarboxylase synthetase deficiency excrete these metabolites in the newborn period, the disorder should be identifiable using this technology. Sensorineural hearing loss has many causes.
Biotinidase deficiency can be excluded as a cause by determining biotinidase enzyme activity in serum. This test should be performed specifically on children with hearing loss who biottinidasa exhibiting other clinical features consistent with biotinidase deficiency. To establish the extent of disease and needs in a symptomatic individual diagnosed with biotinidase deficiency, the following evaluations are recommended:. To establish the extent of disease and needs in infants or children diagnosed with biotinidase deficiency following newborn screeningthe following evaluations are recommended:.
Although newborn screening for biotinidase deficiency has resulted in almost complete ascertainment of children with biotinidase deficiency in the United States and in many other countries, occasionally a child who has not been screened or has been mistakenly thought to have normal biotinidase activity on newborn screening will present with clinical symptoms.
These children may become biotinudasa compromised deficoencia require hydration, occasionally bicarbonate for biotinldasa, and procedures to ameliorate hyperammonemia. Once biotinifasa is recognized that the child has a multiple carboxylase deficiency, administration of biotin — or a multivitamin “cocktail” containing biotin — can rapidly resolve the metabolic derangement bitoinidasa improve many of the clinical symptoms within hours to days. Compliance with biotin therapy see Prevention of Primary Manifestations improves symptoms in symptomatic individuals.
Some features such as optic atrophy, hearing loss, or developmental delay may not be reversible; they should be addressed with ophthalmologic evaluations and intervention, hearing aids or cochlear implants, and appropriate interventions for developmental deficits.
It is therefore strongly recommended that all children with biotinidssa biotinidase deficiency, regardless of the residual biotinidase enzyme activity, be treated with biotin.