Int. J. Neonatal Screen., Volume 1, Issue 1 (June 2015) – 6 articles , Pages 1-56

Background: Biotinidase deficiency is an inherited metabolic disorder that if untreated can result in neurological and cutaneous features. Profound biotinidase deficiency presents in early childhood with severe symptoms, whereas partial biotinidase deficiency can also present with symptoms under times of stress. Symptoms can be prevented by administering biotin. Newborn screening for the disorder is performed using dried blood spots. We examined the relationship between biotinidase activity and age at collection to determine how best to identify infants with partial biotinidase deficiency. Methods: Biotinidase activity in dried blood spots is determined using a quantitative fluorometric assay. Subsequent specimens with biotinidase activity ≤100 U were analyzed by mutation analysis to determine the range of activities expressed in infants with partial biotinidase deficiency. Results: Enzyme activity increased with age, beginning at about three days of age, and rose until plateauing at about 11 days of age. An increase of about 47.6% was observed. A total of 54 specimens had mutation analysis performed identifying 20 affected infants who would not have been identified using the original cutoff activity of 50 U. Conclusion: Biotinidase activity in infants increases with age. Age-related cutoffs assist in selectively identifying infants with partial biotinidase deficiency. Full article

Congenital adrenal hyperplasia (CAH) comprises a group of rare autosomal recessively inherited disorders of cortisol biosynthesis in the adrenal cortex. More than 95% are based on a defect in the CYP21A2 gene causing 21-hydroxylase deficiency. Newborn screening (NBS) for CAH by means of 17-hydroxy-progesterone (17-OHP) determination in dried whole blood on filter paper has been introduced as part of the NBS in many countries worldwide. The goals of CAH screening are early detection of the severe, salt-wasting form, therefore prevention of adrenal crisis or death, early detection of the simple virilizing form, and prevention or shortening of the period of incorrect gender assignment in females. Methodological problems of false-positive samples, especially in pre-term infants, can be corrected by adapting the cut-off values for 17-OHP to birth weight, gestational age and age at the time of collection and by performing a second tier screening. Despite a positive voting for newborn CAH screening by the European Society for Pediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society, it is obvious that the acceptance of CAH screening varies worldwide. Full article

Urea cycle disorders (UCDs) comprise a group of recessive and one X-linked inherited errors of protein metabolism that, due to insufficient detoxification of excess nitrogen, can lead to severe neurological disease. The key feature, but at the same time only a surrogate marker of UCDs, is the resulting mild to severe hyperammonemia. Biochemical analysis is needed to strengthen the suspicion of any underlying UCD but remains for the majority of cases rather indicative than diagnostic due to the lack of definite markers. Thus, in order to confirm a specific UCD, mutation analysis or enzyme assays are the methods of choice. Because of the drastic clinical complications of severe hyperammonemia, an early diagnosis before onset of symptoms would be desirable. The best way to achieve this would be to implement a general newborn screening for these disorders. However, there are several challenges that need to be overcome before newborn screening for UCDs can be introduced. This review will briefly describe the technical and clinical challenges involved in newborn screening for UCDs and will then discuss current experiences with this approach. Full article

Newborn screening is the largest genetic testing effort in the United States and is considered one of the ten great public health achievements during the first 10 years of the 21st century. For over 35 years, the Newborn Screening Quality Assurance Program (NSQAP) at the US Centers for Disease Control and Prevention has helped NBS laboratories ensure that their testing does not delay diagnosis, minimizes false-positive reports, and sustains high-quality testing performance. It is a multi-component program that provides comprehensive quality assurance services for dried blood spot testing. The NSQAP, the Biochemical Mass Spectrometry Laboratory (BMSL), the Molecular Quality Improvement Program (MQIP) and the Newborn Screening Translation Research Initiative (NSTRI), aid screening laboratories achieve technical proficiency and maintain confidence in their performance while processing large volumes of specimens daily. The accuracy of screening tests could be the difference between life and death for many babies; in other instances, identifying newborns with a disorder means that they can be treated and thus avoid life-long disability or severe cognitive impairment. Thousands of newborns and their families have benefited from reliable and accurate testing that has been accomplished by a network of screening laboratories and the NSQAP, BMSL, MQIP and NSTRI. Full article

Today, all of the states in the United States and many countries screen their newborns for biotinidase deficiency. Biotinidase deficiency meets the major criteria for including a disorder into screening programs. However, rarely do we learn the actual story behind the discovery of a disorder where the underlying etiology was elusive or about the events leading to a disorder’s incorporation into a newborn screening program. This is the story of the role that serendipity played in the story of biotinidase deficiency and the newborn screening of the disorder. Full article

“Third time is a charm”, with this adage I would like to introduce the International Journal of Neonatal Screening (IJNS). Why three times? Well, this is the third time that the International Society for Neonatal Screening (ISNS) has launched its official journal. The first one, Screening, began in 1992, one year after the constitution of ISNS. In 1996, after Vol. 4 No.4 was printed, the publication of Screening had to be stopped. It was too expensive for the small number of members, and there were not enough institutional subscriptions (if any at all), that could compensate for the deficit. Since Screening was never indexed, the large number of high quality articles dealing with newborn screening aspects that were published in the four volumes have stayed invisible for most of the scientific community. In 1996 ISNS and the Journal of Medical Screening (JMS) agreed to have JMS as the society’s journal, but unfortunately over the years only a few manuscripts from ISNS members were submitted to JMS. Despite the efforts of ISNS council members, the situation did not change and JMS and the ISNS council decided to discontinue the collaboration from 2002. Since then, ISNS has had no official journal, and the ISNS newsletter has been until now the only forum for information exchange between members. But now, after 13 years of abstinence, ISNS makes a new attempt—the third one.[...] Full article