Hemoglobinopathies

The newborn screening kit for hemoglobinopathy evaluation, Targeted MS/MS Hemo, is a qualitative analytical test for newborn screening for hemoglobin (Hb)-related conditions such as sickle cell disease. This test is based on the detection by mass spectrometry of peptides generated during the digestion of normal Hb and/or variants (HbA, HbA2, HbC, HbDPunjab/Los Angeles, HbE, HbF, HbOArab and HbS) of the patient.

This assay is dedicated to professional use in diagnostic laboratories. The device is not for self-testing.

The principle of the Targeted MS/MS Hemo screening assay is based on a rapid hemoglobin (Hb) extraction and denaturation from patients’ DBS samples before its digestion by trypsin. The digested extract is then analysed by MS/MS, in flow injection analysis mode (FIA), on a “triple quadrupole” system. The MS/MS mode used for this assay is the Multiple Reaction Monitoring (MRM): two product ions are selected by peptide and the twelve peptides are simultaneously detected by scanning the two specific “parent ion/product ion couple” for each.

A dedicated software allows time saving in results analysis. Targeted MS/MS Hemo Software (based on Excel) is used to calculate peptide signals ratios, which are analysed by tree-like algorithms. It facilitates the identification of different medically significant phenotypes.

General information

Format: 96 – 480 determinations
Storage: At 2-8°C
Automated Interpretation: Yes
Turn around time: Around 2.5 hours

Associated Publications

Evaluation of a New Tandem Mass Spectrometry Method for Sickle Cell Disease Newborn Screening: https://pmc.ncbi.nlm.nih.gov/articles/PMC11676960/

High Throughput Testing Method with Newborn’s DBS for Hemoglobinopathies by LCMS-8045 with ZenTech Targeted MS/MS Hemo Device: https://www.shimadzu.com/an/sites/shimadzu.com.an/files/pim/pim_document_file/applications/application_note/21791/an_06-saip-lc-055-en.pdf

Hemoglobinopathies Newborn Screening by LCMS-8050 using ZenTech Targeted MS/MS Hemo device: https://www.zentech.be/assets/0d71e5e6-4073-450a-ae89-dc4669462026/sca-210-064-hemoglobinopathies-newborn-screening-using-zentech-targeted-msms-hemo-device.pdf

Summary of the pathologies detected

Thalassemia syndromes :

Alfa-thalassemia
Beta-thalassemia

Structural Variants :

Sickle cell disease
HBC disease, HBE disease
Carrier or composite heterozygosity for HbS, HbC, HbE, HbD^Punjab, HbO^Arab

Test principle

Sickle Cell Disease is associated with significant morbidity and mortality in young children. Hemoglobinopathies are the most common monogenic pathology worldwide. The number of subjects who are heterozygous carriers is estimated at approximately 7% of the global population. Therefore, each year between 300,000 and 400,000 children are born worldwide with severe hemoglobinopathy.

The onset of major neonatal sickle cell disease is as early as three months of age. The progression of the disease is pronounced by acute complications of three types: vaso-occlusive crises causing intense and sudden pain in certain parts of the body (commonly hands, feet, hips, abdomen), hemolysis and infections.

β-thalassemia major is characterized by chronic hemolytic anemia. Hepatosplenomegaly and skeletal deformities are manifestations of medullary hyperplasia. These patients are also prone to infections and spontaneous fractures.

The benefits of early screening have been clearly demonstrated only for the following phenotypes: Hb SS, Hb SC, Hb SDPunjab, Hb Sβ thalassemia (β+, β0, δβ, Lepore), Hb SOArab and Hb S/HPFH. Early identification through screening allows for timely medical interventions, such as blood transfusions and hydroxyurea therapy, which can significantly reduce the risk of complications and improve overall survival and quality of life. Implementing widespread newborn screening programs for these hemoglobinopathies can thus play a crucial role in reducing the burden of disease globally, especially in regions where these conditions are more prevalent.