Clinical Findings in Four Children with Biotinidase Deficiency Detected through a Statewide Neonatal Screening Program
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.
Available from: Akihiro Yamaguchi
- "All of the recall results were normal, and therefore, no infants with biotinidase deficiency have been identified as yet. The incidence of biotinidase deficiency was estimated to be 1 in 41,000 newborns (Wolf et al. 1985). As no such figure has been reported in Japan up to now, more extensive screening should be carried out. "
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ABSTRACT: A simple and reliable method for quantification of biotinidase (EC.126.96.36.199) activity in dried blood spot was devised by a modification of the colorimetric screening test developed by Heard et al. (1984). The enzyme reaction and hemoglobin denaturation were carried out in a U-bottomed microplate. An aliquot of the reaction solution was transferred to a flat-bottomed microplate. After the coupling reaction was started, the adsorbance was measured in situ by a microplate-reader. Both intra- and inter-assay coefficient of variation (CV) values were less than 10%. Biotinidase activity in dried blood spot showed a good correlation to that in serum (r = 0.912, n = 8). This method was applied in a pilot screening of 18,945 newborns in Sapporo City. No positive results have been obtained as yet.
Available from: William J Rhead
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ABSTRACT: With the rapid expansion of newborn screening to include more newborns and more pathologic conditions comes an additional pool of individuals presenting to primary care providers, community hospitals, or tertiary care genetic centers for follow-up evaluation. With the exception of conditions that have historically been included in screening programs, this population presents with potential disorders that have not previously been encountered with great frequency in asympto- matic patients. For example, in the symptomatic phase, urea cycle disorders would present in the context of severe hyper- ammonemic encephalopathy, methylmalonic aciduria with acute acidosis and encephalopathy, and medium-chain acyl CoA dehydrogenase (MCAD) deficiency with hypoketotic hypoglycemia and liver failure. Metabolic findings in acute circumstances are usually pronounced and enable unequivocal diagnosis. In today's newborn screening environment, there is a high likelihood that neonates will present in an asymptomatic clinical phase of the illness requiring that laboratory tests and those that interpret them detect ever more subtle metabolic abnormalities. In this context, the biochemical genetics laboratory plays a pivotal role in recommending and interpreting initial studies as well as dictating the necessity and type of further testing. The focus of this Chapter, therefore, is not on the diagnostic accuracy of newborn screening per se, but on the sensitivity and specificity of the sophisticated testing applied to infants referred for follow-up of a positive newborn screening result. Primary literature and expert opinion has guided the testing recommendations to follow. The rarity of these disorders gen- erally precludes large, randomized studies of diagnostic accu- racy. An exhaustive review of the literature, primarily case reports and series, were reviewed for evidence of biochemical abnormalities in affected, generally asymptomatic children.
Available from: Michael J Bennett
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