Onze beursstudenten

Dokter Aurélie EMPAIN

Project

Systematic newborn screening for hyperhomocystinemia

Project supervisor

Labo of hospitaal waar het project plaatsvindt

Newborn Screening Laboratory ULB and Hôpital Universitaire des Enfants Reine Fabiola

Objectives of research

The primary objective is to improve newborn screening for homocysteine metabolism disorders, to study the clinical impact of the introduction of a new screening test, namely systematic screening for elevated homocysteine, with the prompt treatment of metabolic diseases.

Secondary objectives will be the optimization of the analysis of homocysteine in MS and the study of the psychological impact of NBS (newborn screening) on the parental stress and therefore on the relationship between parents and their newborn in case of false positive results and in case of diagnosis of a metabolic disease.

Summary

Homocysteinuria and remethylation disorders are relatively rare hereditary metabolic diseases which, if left untreated, can lead to serious alterations in a child's clinical condition. Symptoms include developmental delay, severe behavioral and psychological disorders, as well as ocular and vascular damage. The key metabolic marker is homocysteine, an amino acid derived from methionine. These pathologies are characterized by a marked elevation of homocysteine concentration in the blood of affected patients compared to the general population. In the Wallonia-Brussels federation, the ONE neonatal screening program includes screening for classical homocysteinuria. However, for technical reasons, screening is based on a search for abnormal methionine levels, as direct measurement of homocysteine levels is not possible on the dried blood samples used for neonatal screening. As a result, the sensitivity of screening is not optimal, leading to a high healthy-child recall rate (poor specificity of methionine for pathology), but also a high falsenegative rate, as vitamin B6-sensitive forms of classic homocysteinuria only induce a minor elevation of methionine. In addition, other remethylation disorders are linked to low methionine levels, and are therefore not detected by the ONE neonatal screening program. The aim of this work is to develop and validate a method for the direct determination of homocysteine levels in dried blood samples from newborn screening, so that homocysteine can be used as an indicative marker for homocystinuria and remethylation disorders. The technical validation of this method in the laboratory will be followed by a clinical validation of this new screening method for homocystinuria and remethylation disorders. To this end, a clinical study will be carried out, including a convocation of newborns with high homocysteine levels - which may also be linked to severe vitamin B12 deficiency. The value of newborn screening by measuring homocysteine levels will be assessed in terms of the expected clinical benefits for the children screened, as well as the psychological impact of such screening in the event of positive and false-positive results.