Once the BTD pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for biotinidase deficiency are possible.
Compliance with biotin therapy see Prevention of Primary Manifestations improves symptoms in symptomatic individuals. It is therefore strongly recommended that all children with profound biotinidase deficiency, regardless of the residual biotinidase enzyme activity, be treated with biotin.
While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate. To administer biotin to an infant or young child, the tablet can be crushed or the contents of the capsule can be mixed with breast milk or formula in a spoon, medicine dispenser, or syringe.
Family planning The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
The BTD gene has 4 exons of lengths 79 bp, bp, bp and bp, respectively. Depending on the amount of residual biotinidase activity, individuals can have either profound or partial biotinidase deficiency. In the United States, molecular prenatal testing is available and preferred.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. See Molecular Genetics for information on allelic variants detected in this gene.
The genetic status of any relative with symptoms consistent with biotinidase deficiency should be clarified by assay of biotinidase enzyme activity or molecular genetic testing if the BTD pathogenic variants in the family are known so that biotin therapy can be instituted in a timely manner.
In addition to beta-hydroxyisovalerate, elevated concentrations of urinary lactate, methylcitrate, and beta-hydroxypropionate are indicative of the multiple carboxylase deficiencies, including the above disorders and propionic acidemia and pyruvate carboxylase deficiency.
High-dose biotin therapy is extremely efficacious in both conditions. While genotype-phenotype correlations are not well established, it appears that certain mutations are associated with profound biotinidase deficiency, while others are associated with partial deficiency.
This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. Other family members of a proband. S Epub Nov 20 4. Mode of Inheritance Biotinidase deficiency is inherited in an autosomal recessive manner.
Therefore, measurement of the biotinidase enzyme is required to differentiate between these diseases and ensure proper diagnosis. Clinical Reference Recommendations for in-depth reading of a clinical nature 1.
Definitive enzyme determinations are required to distinguish between the two disorders: Biotinidase is the enzyme that is made by the BTD gene. One study pointed out that untreated individuals may not show symptoms until age Biotinidase deficiency can be excluded as a cause by determining biotinidase enzyme activity in serum.
These alleles are considered profound biotinidase deficiency alleles; a combination of two such alleles, whether homozygous or compound heterozygousresults in profound biotinidase deficiency. Only a few anecdotal reports exist regarding symptoms in children with partial biotinidase deficiency who were not treated with biotin.
Therefore, measurement of the biotinidase enzyme is required to differentiate between these diseases and ensure proper diagnosis.
Diagnosis[ edit ] Biotinidase deficiency can be found by genetic testing. Infants with severe deficiency of holocarboxylase synthase become ill in the newborn period. In both disorders, these activities increase to near-normal or normal after biotin treatment.
A case study from Metametrix  detailed the effects of biotin deficiency, including aggression, cognitive delay, and reduced immune function.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. Biotinidase deficiency Methodology Help The assay's major method category (biochemical, cytogenetic or molecular genetics); method category (i.e. enzyme assay, chromosome breakage studies, targeted mutation analysis); methodology (i.e.
the name of the method used) and instruments used when performing this test. Mutation analysis of the entire biotinidase gene is rarely necessary, because there are no therapeutic consequences with the exception of individuals with partial biotinidase deficiency in which targeted mutation analysis may be helpful (Wolf, ).
Clinical Information. Biotinidase deficiency is an inherited metabolic disease caused by reduced levels of biotinidase, an enzyme that recycles biotin by releasing it from its metabolic product, biocytin, or exogenous dietary proteins.
BTDZ: Biotinidase deficiency is an inherited metabolic disease caused by reduced levels of biotinidase, an enzyme that recycles biotin by releasing it from its metabolic product, biocytin, or exogenous dietary proteins.
Biotin is a vitamin that serves as a coenzyme for 4 carboxylases that are essential for amino acid catabolism, gluconeogenesis, and fatty. 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.