Biotinidase deficiency: Initial clinical features and rapid diagnosis

Abstract

Biotinidase deficiency is the primary defect in most individuals with late-onset multiple carboxylase deficiency. We have reviewed the presenting clinical features of 31 children with the disorder. Seizures, either alone or with other neurological or cutaneous findings, are the most frequent initial symptom observed. Other neurological symptoms, such as hypotonia, ataxia, hearing loss, optic atrophy, and developmental delay, are seen, in addition to skin rash and alopecia. The disorder is also characterized by ketolactic acidosis and organic aciduria. Biotinidase activity may be diagnosed using a simple, rapid, semiquantitative colorimetric procedure. Samples of whole blood spotted on the same filter paper used by most states to screen for phenylketonuria and other inborn errors of metabolism may be sent to an appropriate reference laboratory. None of the common anticonvulsants or sedatives used to treat newborns and children interfere with the test. Because biotinidase deficiency can be treated readily with biotin, this disorder should be considered in children with infantile seizures, especially in the presence of other characteristic neurological or cutaneous features.

Cost-Effectiveness Analysis of a National Newborn Screening Program for Biotinidase Deficiency

“…[1][2][3] Biotinidase deficiency (BD) is an autosomal recessive inherited disorder in which the enzyme, biotinidase, is defective and the vitamin, biotin, is not recycled. 4 This disorder can be categorized as profound BD (,10% of mean normal activity in serum) and partial BD (10%-30% of normal activity).…”

“…Symptoms of untreated BD usually appear between 1 week and 10 years, with a mean age of 3.5 months. 3 We assume that acute episodes of seizures, skin problems, and hypotonia, when they occur, appear during the first year of life, whereas cognitive deficit, optic atrophy, and sensorineural hearing loss would become apparent in the second year of life, varying this last parameter between 2 and 15 years of age in the sensitivity analysis. …”

Biotinidase deficiency: “if you have to have an inherited metabolic disease, this is the one to have”

“…2,24 Metabolically, most untreated individuals with biotinidase deficiency will have one or more of the following: ketolactic acidosis, organic aciduria, and mild hyperammonemia. 24,25 However, the absence of organic aciduria or metabolic ketoacidosis does not exclude the diagnosis of biotinidase deficiency in a symptomatic child. Symptoms of untreated profound biotinidase deficiency usually appear between the ages of 1 week and 10 years, with a mean age of 3.5 months.…”

“…Symptoms of untreated profound biotinidase deficiency usually appear between the ages of 1 week and 10 years, with a mean age of 3.5 months. 25 Some children with biotinidase deficiency exhibit only a single symptom, whereas others have multiple neurological, cutaneous, or biochemical findings.…”

“…2,6,[25][26][27] The seizures are usually myoclonic, but may be grand mal and focal; some children have infantile spasms. 28 Some untreated children have exhibited spinal cord disease characterized by progressive spastic paresis and myelopathy.…”