|
Biotinidase deficiency is an autosomal recessive metabolic disorder in which biotin is not released from proteins in the diet during digestion or from normal protein turnover in the cell. This situation results in biotin deficiency. Biotin, sometimes called vitamin B7, is an important water-soluble nutrient that aids in the metabolism of fats, carbohydrates and proteins. Biotin deficiency can result in behavioral disorders, lack of coordination, learning disabilities and seizure. Biotin supplementation can alleviate and sometimes totally arrest such symptoms.
Epidemiology Based on the results of worldwide screening of biotinidase deficiency in 1991, the incidence of the disorder is: - One in 137,401 for profound biotinidase deficiency
- One in 109,921 for partial biotinidase deficiency
- One in 61,067 for the combined incidence of profound and partial biotinidase deficiency
- Carrier frequency in the general population is approximately one in 120.
Symptoms Symptoms of a biotinidase deficiency can appear several days after birth. These include: seizures, hypotonia and muscle/limb weakness, ataxia, paresis, hearing loss, optic atrophy, skin rashes (including seborrheic dermatitis and psoriasis), and alopecia. If left untreated, the disorder can rapidly lead to coma and death. Biotinidase deficiency can also appear later in life. This is referred to as "late-onset" biotinidase deficiency. The symptoms are similar, but perhaps more mild, because if an individual survives the neonatal period they likely have some residual activity of biotin-related enzymes. Studies[1][2] have noted individuals who were asymptomatic until adolescence or early adulthood. One study pointed out that untreated individuals may not show symptoms until age 21.[3] Furthermore, in rare cases, even individuals with profound deficiencies of biotinidase can be asymptomatic.[1] Symptom severity is predictably correlated with the severity of the enzyme defect. Profound biotinidase deficiency refers to situations where enzyme activity is 10% or less.[2] Individuals with partial biotinidase deficiency may have enzyme activity of 10-30%.[2] Functionally, there is no significant difference between dietary biotin deficiency and genetic loss of biotin-related enzyme activity. In both cases, supplementation with biotin can often restore normal metabolic function and proper catabolism of leucine and isoleucine. The symptoms of biotinidase deficiency (and dietary deficiency of biotin) can be quite severe. A 2004 case study from Metametrix [4] detailed the effects of biotin deficiency, including aggression, cognitive delay, and reduced immune function. Dietary Concerns It is recommended that raw eggs should be avoided in those affected by biotin deficiency, because egg whites contain high levels of avidin. The name avidin literally means that the protein has an "avidity" for "biotin." Avidin binds to biotin, making it unavailable for use elsewhere in the body, and otherwise useful biotin molecules are excreted in the urine. Genetics  Biotinidase deficiency has an autosomal recessive pattern of inheritance. Individuals lacking functional biotinidase enzymes can still have normal carboxylase activity if they ingest adequate amounts of biotin. The standard treatment regimen calls for 5 10 mg of biotin per day.[5] Biotinidase deficiency is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the defective gene - one from each parent - must be inherited for a person to be affected by the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder, but are carriers of one copy of the defective gene. If both parents are carriers for the biotinidase deficiency, there is a 25% chance that their child will be born with it and a 75% chance that they will be carriers. The chromosomal locus is at 3p25. The BTD gene has 4 exons of lengths 79 bp, 265 bp, 150 bp and 1502 bp, respectively. There are at least 21 different mutations that have been found to lead to biotinidase deficiency. The most common mutatations in severe biotinidase deficiency (<10% normal enzyme activity) are: p.Cys33PhefsX36, p.Gln456His, p.Arg538Cys, p.Asp444His, and p.[Ala171Thr;Asp444His]. Almost all individuals with partial biotinidase deficiency (10-30% enzyme activity) have the mutation p.Asp444His in one allele of the BTD gene in combination with a second allele.[6] Diagnosis Biotinidase deficiency can be found by genetic testing. This is often done at birth as part of newborn screening in several states throughout the United States. Results are found through testing a small amount of blood gathered through a heel prick of the infant. As not all states require that this test be done, it is often skipped in those where such testing is not required. Biotinidase deficiency can also be found by sequencing the BTD gene, particularly in those with a family history or known familial gene mutations. Pathophysiology Symptoms of the disease are caused by the inability to reuse biotins that are needed for cell growth, production of fatty acids and the metabolism of fats and amino acids. For the most part, there is no real progression. If left untreated, the symptoms can lead to later problems such as comas or death. The problems that are prevalent early in life remain prevalent in old age unless treatment is administered daily. Treatment Treatment is possible but unless continued daily, problems may arise. Currently, this is done through the taking of 5 10 mg of oral biotin a day. If symptoms have begun to show, standard treatments can take care of them, such as hearing aids for poor hearing. Disease Database BTD gene variant database See also References Further reading External links de:Biotinidasemangel nl:Biotinidasedefici ntie
| 
Encyclopedia
top
