Characteristics and outcomes of patients with formiminoglutamic aciduria detected through newborn screening

Abstract

Summary Background Glutamate formiminotransferase deficiency (FTCD deficiency) or formiminoglutamic aciduria is the second most common of the known inherited disorders of folate metabolism. Initial case reports suggested that patients may have severe intellectual disability and megaloblastic anemia. However, these cases were obtained from screening cohorts of patients with developmental delay. Subsequently, patients with milder clinical phenotypes have been reported. The full phenotypic spectrum of this disorder remains unknown. Methods In many states, FTCD deficiency can be incidentally detected on tandem mass spectrometrybased newborn screening of dried blood spots. In this work, we report the outcomes of infants identified to have FTCD deficiency through newborn screening. Results During the study period, 18 patients were identified to have FTCD deficiency and were referred and evaluated at one of the two participating metabolic centers. The overall rate of FTCD deficiency detected through the New Jersey screening program over the study time period was 1:58,982. At a mean age of 56 months at last follow-up, 3/18 (16%) had developmental delays requiring individualized education plans; no patients had profound intellectual disability. 4/16 (25%) had mild self-limited anemia; no patients had profound anemia. Conclusions These data suggest that the majority of individuals with FTCD deficiency detected by newborn screening are asymptomatic.

Formimidoyltransferase cyclodeaminase prevents the starvation-induced liver hepatomegaly and dysfunction through downregulating mTORC1

“…Among all the FTCD deficiency patients, the cases displaying symptoms are limited. Recently, a tandem mass spectrometry-based newborn screen suggested that the majority of individuals with FTCD deficiency were asymptomatic [44]. That is consistent with the ftcd mutant zebrafish under normal feedings.…”

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…Continuing to expand NBS, SMA was added to the screening panel on 30 August 2023 by the National Board of Health and Welfare policy development [ 1038 ]. Regarding other conditions, a study developed G6PD incidence data and found that NBS was probably not warranted [ 1039 ], two studies looked at the possibility of analyzing DBSs for phosphatidylethanol, an alcohol biomarker [ 1038 , 1040 ], and another study looked at the characteristics and outcomes of patients with formiminoglutamicc aciduria detected through NBS [ 1041 ]. In the long term, NBS may be significantly impacted by a new project, Screen4Care, which draws on a collaboration of 21 academic partners, 9 industrial project partners, and 4 small- and medium-sized enterprises to initiate a multi-pronged strategy to shorten the time to diagnosis and treatment for patients with rare diseases through genetics and artificial intelligence [ 1042 ].…”

Quantification of Differential Metabolites in Dried Blood Spots Using Second-Tier Testing for SCADD/IBDD Disorders Based on Large-Scale Newborn Screening in a Chinese Population

“…Nevertheless, increasing concentrations of methylsuccinic acid (MSA) concentration serves as a special biochemical marker for EE (8), and elevations in OX-2acetoacetic acid, isovalanyl glycine-2,2-hydroxyisobutyric acid-2, and adipic acid to extremely high levels are observed in GA2 (9). In some cases of FIGLU, formiminoglutamate is observed in biological fluids after histidine loading (10). Therefore, a novel second-tier screening method involving the use of UPLC-MS/MS can detect the secondary targets ethylmalonic acid (EMA) and isobutyryl-glycine (IBG), which are part of the differential diagnosis or profile review of screening for primary targets (11,12).…”