A 7-Year Report of Spectrum of Inborn Errors of Metabolism on Full-Term and Premature Infants in a Chinese Neonatal Intensive Care Unit

Abstract

Inborn errors of metabolism (IEMs) have great repercussions in neonatal intensive care units (NICUs). However, the integrative analysis of the incidence for full-term and premature neonates of IEMs in NICUs have not been reported. In this study, we aimed to estimate the incidence of IEMs in the NICU population so as to better evaluate the impact of IEMs on Chinese NICUs. A total of 42,257 newborns (proportion of premature as 36.7%) enrolled to the largest Chinese NICU center for a sequential 7 years screen, and 66 were diagnosed with IEMs. The prevalence of IEMs in total, full-term, and premature infants was 1:640, 1:446, and 1:2,584, respectively. In spectrum of our NICU, diseases that cause endogenous intoxication like methylmalonic acidemia accounted for 93.9% (62/66), and this ratio was higher in full-term infants with 98.3% (59/60), while the most prevalent disease in premature newborn was hyperphenylalaninemia (50%, 3/6), respectively. The genetic analysis of 49 cases revealed 62 potentially pathogenic mutations in 10 well-documented pathogenic genes of IEMs, among which 21 were novel. In conclusion, differences in incidence and spectrum of full-term and premature births we obtained in NICU will provide diagnostic guidelines and therapeutic clues of neonatal IEMs for pediatricians. Keywords: newborn screening, neonatal intensive care unit, inborn errors of metabolism, incidence of inborn errors of metabolism, spectrum of genes and mutations

Frequency of carriers for rare metabolic diseases in a Brazilian cohort of 320 patients

“…We have estimated the frequency of rare recessive metabolic diseases to be 10.96 per 10,000 people. Other studies using different methodologies have estimated variable frequencies of metabolic disorders: 4.0 (40/100,000) [11], 12,76 (1/784) [12] or 15.6 (66/42,257) [13] per 10,000 people. These estimates, though, are usually challenging especially if they are based on biochemical-based newborn screening programs because several factors may in uence the results, including the scope of diseases screened, deaths occurring before a diagnosis is made, ease of access for screening programs, diagnosis con rmation methods, speci c regional clinical interests [12].…”

NeoSeq: a new method of genomic sequencing for newborn screening

“…It is certain that the advantages of nGS primarily include fewer false-positive results, accurate diagnosis and distinction of disorders, and more useful information for newborn life. Due to the high sensitivity of TMS, the high false-positive rate and low positive predictive value of TMS are always a problem, particularly for some special populations such as premature infants [21]. Additionally, the technique is easily affected by external interference [22].…”

NeoSeq: A New Method of Genomic Sequencing for Newborn Screening

“…It is certain that the advantages of nGS primarily include fewer false-positive results, accurate diagnosis and distinction of disorders, and more useful information for newborn life. Due to the high sensitivity of TMS, the high false-positive rate and low positive predictive value of TMS are always a problem, particularly for some special populations such as premature infants 20 . Additionally, the technique is easily affected by external interference 21 .…”