Biotinidase deficiency

It is an inborn error of metabolism that causes symptoms such as seizures, difficulty breathing, hypotonia, skin rashes, alopecia, hearing loss and developmental delay.

Biotin, vitamin H or B7 is a water-soluble vitamin that belongs to the B group and should be incorporated in the diet. It is an essential nutrient for the correct functioning of the brain. In food, this vitamin is usually found bound to proteins, so it is not directly accessible. To release biotin from the proteins that bind it, the pancreas of mammals produces the enzyme biotinidase.

Biotinidase deficiency is caused by pathogenic variants in the gene encoding it, called BTD, resulting in reduced or absent activity of the enzyme, leading to a reduced ability to absorb biotin from the diet.

The prevalence of biotinidase deficiency is estimated at 1 in 61,000 individuals and the frequency of carriers in the general population is approximately 1 in 120 people. It is a disease that is included in neonatal screening in many countries.

Symptoms

Symptoms usually appear between two weeks and two years, but cases of patients who have developed the disease much later have also been observed. There are two clinical manifestations, one more severe and one more moderate depending on the levels of biotinidase activity.

Individuals with profound biotinidase deficiency who are not treated from infancy and have less than 10% of the average normal serum biotinidase activity have variable symptoms such as developmental delay, ataxia, seizures, hypotonia, skin abnormalities (eczematous rashes, alopecia, candidiasis), hearing loss and visual problems. Metabolically, untreated children may show ketolactic acidosis, organic acidemia (aciduria) and hyperammonemia.

Individuals with untreated partial BTD deficiency who have an average BTD activity of 10-30% are usually asymptomatic, but during periods of stress, such as illness, fever or fasting, they may develop symptoms similar to those of individuals with profound BTD deficiency, which are usually more moderate.

Disease management

Children who are identified by neonatal screening and immediately treated with biotin throughout their lives remain asymptomatic.

They should have regular check-ups to assess their vision and hearing. Follow-up with a physician specializing in metabolism.

It is recommended to avoid the consumption of raw eggs as they contain avidin, as well as egg whites. Avidin binds strongly to biotin reducing its bioavailability.

Genes analyzed

BTD

Bibliography

León-Del-Río A. Biotin in metabolism, gene expression, and human disease. J Inherit Metab Dis. 2019 Jul;42(4):647-654.

Norrgard KJ, Pomponio RJ, Hymes J, et al . Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children. Pediatr Res. 1999 Jul;46(1):20-7.

Wolf B. Biotinidase Deficiency. 2000 Mar 24 [updated 2016 Jun 9]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.

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