Outcomes of four patients with homocysteine remethylation disorders detected by newborn screening

Abstract

Purpose:We evaluated the clinical outcome in homocysteine remethylation disorders following newborn screening (NBS) and initiation of early specific treatment. Methods:Five patients with remethylation disorders were included in this study. Results:Two asymptomatic patients (one with cblG and one with cblE) were identified by NBS using an approach that combines a postanalytical interpretive tool (available on the Region 4 Stork (R4S) collaborative project website, http://www.clir-r4s.org) and a second-tier test for total homocysteine determination. Both the initial screening and the second-tier test are performed on the same blood spot, with no additional patient contact, resulting in no false-positive outcomes. Two additional patients with methylenetetrahydrofolate reductase deficiency were detected by NBS using low methionine as a marker.Although already symptomatic despite the early diagnosis, the latter two patients greatly improved with treatment and their outcomes are compared with that of another patient with methylenetetrahydrofolate reductase deficiency and significant morbidity who was diagnosed clinically at 3 months of age. Conclusion:Early detection by NBS and timely and specific treatment considerably improve at least short-term outcomes of homocysteine remethylation disorders. When a remethylation disorder is suspected, group-specific treatment could be started prior to the completion of in vitro confirmatory testing because all disorders from this group require similar intervention.

Guidelines for diagnosis and management of the cobalamin‐related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

“…Eye disease seems not to be responsive (Huemer et al 2014). Early detection by NBS and timely treatment improved short-term outcomes of two asymptomatic patients with the cblE and cblG defect and three symptomatic patients with MTHFR deficiency (Wong et al 2016). Moreover, early betaine treatment has a clear positive impact on outcome in MTHFR deficiency (Diekman et al 2014).…”

High incidence of maternal vitamin B12 deficiency detected by newborn screening: first results from a study for the evaluation of 26 additional target disorders for the German newborn screening panel

“…Recent improvements in diagnostics and therapeutics suggest an extension of the existing screening panel [1]. For example, there is conclusive evidence for the benefit of early identification by NBS and consecutive early treatment for patients with homocystinuria due to cystathionine ß-synthase (CBS) deficiency, remethylation disorders, especially severe methylenetetrahydrofolate reductase (MTHFR) deficiency, and some disorders of intracellular cobalamin (Cbl) metabolism [2][3][4]. In addition, for severe maternal vitamin B 12 deficiency, a clear benefit of early detection and treatment is evident for both child and mother [5][6][7].…”

A Rapid Screening Method for the Measurement of Neonatal Total Homocysteine in Dried Blood Spots by Liquid Chromatography-Tandem Mass Spectrometry

“…However, since vitamin B12 is not currently measured as part of the routine newborn program in Qatar, this provides a means of detecting at least some cases of vitamin B12 deficiency that may otherwise go undiagnosed. In addition to HCU, elevations of tHCY can also be indicative of other primary inborn errors of metabolism, such as the cobalamin group of disorders, and possibly secondary dietary deficiencies of pyridoxine and folic acid [13,18,32].…”