Clinical Findings in Four Children with Biotinidase Deficiency Detected through a Statewide Neonatal Screening Program

Abstract

Four children with biotinidase deficiency were identified during the first year of a neonatal screening program for this disease in the Commonwealth of Virginia. Two unrelated probands were identified among the 81,243 newborn infants who were screened. In addition, two siblings of one of these infants were found to be affected. Both probands had mild neurologic symptoms at two and four months, respectively, and the two older children had more severe neurologic abnormalities, cutaneous findings, and developmental delay at two and three years of age. However, none of the affected children had acute metabolic decompensation. Previous studies have shown that the administration of biotin to affected children can be a lifesaving procedure that can reverse acute symptoms and prevent irreversible neurologic damage. Our findings demonstrate that subtle neurologic abnormalities may appear as early as at two months of age and that developmental abnormalities may occur even in the absence of episodes of overt metabolic decompensation. Since screening and treatment are both inexpensive and effective and the incidence of the disease is well within the range of that of other metabolic diseases for which screening is performed, biotinidase deficiency should be added to the group of metabolic diseases for which screening is done in the neonatal period.

Outcomes of individuals with profound and partial biotinidase deficiency ascertained by newborn screening in Michigan over 25 years

“…6,7 The first newborn screening for biotinidase deficiency was initiated in Virginia in 1984. 8 The state of Michigan began screening in 1988. However, even though many states have been screening for a relatively long period of time, few studies have been reported that have examined the outcomes of the individuals identified by newborn screening.…”

Laboratory diagnosis of biotinidase deficiency, 2017 update: a technical standard and guideline of the American College of Medical Genetics and Genomics

“…50 Biotinidase deficiency meets many of the criteria for inclusion in state newborn screening programs: there is an inexpensive and reliable screening test, the disorder is associated with high morbidity and mortality if untreated, an easy and effective treatment exists, and the population incidence is comparable to that of other disorders screened. 51 Several studies have shown the cost-effectiveness of screening for both profound and partial biotinidase deficiency. [52][53][54] Currently, all newborn screening programs in the United States and more than 30 other countries screen for biotinidase deficiency, with multiple recent studies suggesting that additional countries are considering incorporation of biotinidase deficiency into their newborn screening programs.…”

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

“…Enzyme activity is either determined using a colorimetric assay, in which biotiniyl-p-aminobenzoate is the substrate, or using a fluorimetric assay, in which biotinyl-6-aminoquinoline is usually the substrate. 15,[60][61][62][63] If an individual is being treated with sulfa medications, false-negative results can occur when using the assay where biotinyl-p-aminobenzoate is the substrate 15 ; fortunately, sulfa medications are contraindicated for biotin concentrations are useful in differentiating among biotin deficiency, biotinidase deficiency, and holocarboxylase synthetase deficiency, but it is important to know the method used for determining the biotin concentration. 2 Only methods that distinguish biotin from biocytin or bound biotin yield reliable estimates of free biotin concentrations.…”