Newborn screening for fatty acid oxidation disorders in a southern Chinese population.

Background and aims: Fatty acid oxidation disorders (FAODs) are a group of autosomal recessive metabolic diseases included in many newborn screening (NBS) programs, but the incidence and disease spectrum vary widely between ethnic groups. We aimed to elucidate the incidence, disease spectrum, and genetic features of FAODs in a southern Chinese population. Materials and methods: The FAODs screening results of 643,606 newborns from 2014 to 2022 were analyzed. Results: Ninety-two patients were eventually diagnosed with FAODs, of which 61 were PCD, 20 were MADD, 5 were SCADD, 4 were VLCADD, and 2 were CPT-IAD. The overall incidence of FAODs was 1:6996 (95 % CI: 1:5814-1:8772) newborns. All PCD patients had low C0 levels during NBS, while nine patients (14.8 %) had normal C0 levels during the recall review. All but one MADD patients had elevated C8, C10, and C12 levels during NBS, while eight patients (40 %) had normal acylcarnitine levels during the recall review. The most frequent SLC22A5 variant was c.760C > T (p.R254*) with an allele frequency of 29.51 %, followed by c.51C > G (p.F17L) (17.21 %) and c.1400C > G (p.S467C) (16.39 %). The most frequent ETFDH variant was c.250G > A (p.A84T) with an allelic frequency of 47.5 %, followed by c.524G > A (R175H) (12.5 %), c.998A > G (p.Y333C) (12.5 %), and c.1657T > C (p.Y553H) (7.5 %). Conclusion: The prevalence, disease spectrum, and genetic characteristics of FAODs in a southern Chinese population were clarified. PCD was the most common FAOD, followed by MADD. Hotspot variants were found in SLC22A5 and ETFDH genes, while the remaining FAODs showed great molecular heterogeneity. Incorporating second-tier genetic screening is critical for FAODs.

Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening.

BACKGROUND: Primary carnitine deficiency (PCD) is an autosomal recessive disorder of carnitine transportation that leads to impaired fatty acid oxidation. Large-scale studies on newborn screening (NBS) for PCD are limited. This study aimed to investigate the biochemical and genetic characteristics of patients with PCD detected through NBS. RESULTS: A total of 548 247 newborns were screened for PCD between January 2014 and June 2021; 1714 newborns with low free carnitine (C0) levels were called back and 49 patients were diagnosed with PCD. The latest incidence rate in Quanzhou, China, was estimated to be 1 in 11 189 newborns. NBS results showed that the 49 patients had varying degrees of decreased C0 levels, whereas seven patients exhibited normal C0 levels during the recall review. All patients harbored biallelic pathogenic variants of the SLC22A5 gene. Nineteen distinct SLC22A5 variants were detected in these 49 patients, and most of the detected variants were clustered in exons 1, 4, and 7. The top eight variants had an allele frequency of 86.73%. The most common variant was c.760C > T (p.R254*) with an allele frequency of 31.63%, followed by c.51C > G (p.F17L) (17.35%) and c.1400C > G (p.S467C) (16.33%). The C0 level of patients with the N/N genotype was significantly lower than that of the M/M group. The C0 levels of patients with genotypes of R254*/R254* and R254*/F17L were far lower than those of patients with the R254*/S467C genotype. CONCLUSIONS: This study presented more than 500,000 NBS data with the latest incidence of 1:11 189 in the Quanzhou area. The SLC22A5 variant spectrum in the selected southern Chinese population has been updated. Patients with null variants were associated with low C0 levels. Combining NBS with genetic testing is critical to improve screening efficiency because patients with PCD may have normal C0 levels during NBS and recall review.

Is preterm donor milk better than preterm formula for very-low-birth-weight infants?

BACKGROUND: Preterm human milk has advantages over preterm formula (PF), but it may compromise some functions after pasteurization. OBJECTIVE: To explore the effects of preterm donor milk (DM) on growth, feeding tolerance, and severe morbidity in very-low-birth-weight infants. METHOD: This was a single-center, prospective cohort study that included 304 preterm infants weighing <1,500 g or of gestational age <32 weeks. If the mother's own milk was insufficient, the parents decided to use PF (n = 155) or DM (n = 149). The two groups were uniformly managed according to the standard NICU protocol. Growth parameters, feeding tolerance, and severe morbidity such as necrotizing enterocolitis, were compared between the two groups. RESULTS: The daily weight gain and weekly head growth in the DM group were not different from those in the PF group (P > 0.05). Feeding intolerance in the DM group was significantly lower than that in PF group (P < 0.05), and parenteral nutrition time and hospitalization time were also shorter than that in the PF group (P < 0.05). Moreover, the incidence of necrotizing enterocolitis and sepsis was also significantly lower in the DM group (P < 0.05). CONCLUSION: The study indicated that preterm DM does not affect the growth of very-low-birth-weight infants. Further, it significantly reduces feeding intolerance, helps achieve full enteral feeding early, and has protective effects against necrotizing enterocolitis and sepsis. Thus, compared with formula, preterm DM can lower the rate of infection in preterm infants and is worthy of promotion.