Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan

Summary

Inborn errors of metabolism (IEM) are not have specific clinical signs, they masquerade as other diseases, and are difficult to diagnose using only clinical manifestations or routine laboratory tests. IEM most commonly manifest in early infancy and childhood. Despite the fact that most IEM are rare in the population, they occupy one of the first places in the structure of childhood pathology, early infant mortality and disability. IEM often remains undiagnosed, while timely diagnosis and timely treatment started can prevent severe systemic damage leading to death and disability. The appointment of a special treatment (diet therapy, cofactors, enzyme replacement therapy) prevents or significantly inhibits the development of the pathological process, especially if the diagnosis is made in the early stages of the disease. To start pathogenetic treatment as early as possible, it is necessary to diagnose IEM as accurately and as early as possible.

Among the diseases included in mass screening programs IEM are especially important due to the development of disability and early mortality in the absence of timely diagnosis and treatment, as well as a high risk of recurrence in burdened families. In this connection, the main goals of mass screening - the prevention of disability in children and the reduction of early infant mortality - dictate the need to introduce modern technologies for preclinical diagnosis of IEM.

Based on the results of the study, it is planned to scientifically substantiate the need for the introduction of selective screening of children for hereditary metabolic diseases using the technology of tandem mass spectrometry in the Republic of Kazakhstan for timely diagnosis, therapy of IEM and prevention of disability. The introduction of a selective newborn screening program for IEM should always be preceded by a study aimed at studying the prevalence of the disease in a certain region, determining regional reference values of the studied metabolites. Local incidence and outcome data can be used to persuade health officials to prioritize screening in health care spending.

The main scientific question and hypothesis of the project is whether it is necessary to introduce tandem mass spectrometry technology in the neonatal screening program for IEM.

Conditions

• Propionic/Methylmalonic Acidemias
• Maple Syrup Urine Disease
• Citrullinemia
• Argininosuccinic Aciduria
• Ornithine Transcarbamylase Deficiency
• Carbamoyl Phosphate Synthetase I Deficiency
• N-acetylglutamate Synthase Deficiency
• Nonketotic Hyperglycinemia
• Tyrosinemia
• Homocystinuria
• Arginase Deficiency
• Isovaleric Acidemia
• Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency
• Isobutyryl-CoA Dehydrogenase Deficiency
• Glutaric Acidemia Type I
• 3-methylcrotonyl-CoA Carboxylase Deficiency
• Biotinidase Deficiency
• Malonyl-CoA Decarboxylase Deficiency
• Beta-ketothiolase Deficiency
• 3-hydroxy-3-methylglutaryl-CoA Lyase Deficiency
• 3-methylglutaconyl-CoA Hydratase Deficiency
• Medium-chain Acyl-CoA Dehydrogenase Deficiency
• Very Long-chain Acyl-CoA Dehydrogenase Deficiency
• Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency
• Glutaric Acidemia Type II
• Primary Carnitine Deficiency
• Carnitine Palmitoyltransferase I Deficiency
• Carnitine Palmitoyltransferase II Deficiency
• Carnitine-acylcarnitine Translocase Deficiency

Interventions

DIAGNOSTIC_TEST

Obtaining Dry Blood Spots From Healthy Newborns (Aged 1-7 Days)

Neonatal blood samples will be taken from healthy infants no earlier than 3 hours after feeding by heel prick with a heel stick. Five drops of whole blood (\~75 µl each) will be applied to Guthrie cards, Ahlstrom 226 filter paper, PerkinElmer 226 Five-Spot Card (PerkinElmer Health Sciences, Greenville, USA) to form dried blood spots (DBSs) for LC-MS/MS analysis. Samples will be dried for 4 hours at room temperature and then stored at 4°C in individually labeled zippered plastic bags with desiccants or other sealed containers until analyzed by LC-MS/MS in accordance with standards from the Institute of Clinical and Laboratory Standards.

DIAGNOSTIC_TEST

Obtaining Dry Blood Spots From Healthy Children Aged 8 Days - 7 Years

Blood samples will be taken from healthy childrens no earlier than 3 hours after feeding by heel prick with a heel stick. Five drops of whole blood (\~75 µl each) will be applied to Guthrie cards, Ahlstrom 226 filter paper, PerkinElmer 226 Five-Spot Card (PerkinElmer Health Sciences, Greenville, USA) to form dried blood spots (DBSs) for LC-MS/MS analysis. Samples will be dried for 4 hours at room temperature and then stored at 4°C in individually labeled zippered plastic bags with desiccants or other sealed containers until analyzed by LC-MS/MS in accordance with standards from the Institute of Clinical and Laboratory Standards

DIAGNOSTIC_TEST

Obtaining Dry Blood Spots From Healthy Children Aged 8-18 Years

Blood samples will be taken from healthy childrens no earlier than 3 hours after feeding by heel prick with a heel stick. Five drops of whole blood (\~75 µl each) will be applied to Guthrie cards, Ahlstrom 226 filter paper, PerkinElmer 226 Five-Spot Card (PerkinElmer Health Sciences, Greenville, USA) to form dried blood spots (DBSs) for LC-MS/MS analysis. Samples will be dried for 4 hours at room temperature and then stored at 4°C in individually labeled zippered plastic bags with desiccants or other sealed containers until analyzed by LC-MS/MS in accordance with standards from the Institute of Clinical and Laboratory Standards

DIAGNOSTIC_TEST

Obtaining Dry Blood Spots From High-risk Newborns (Aged 1-7 Days)

Blood samples will be taken from high-risk infants no earlier than 3 hours after feeding by heel prick with a heel stick. Five drops of whole blood (\~75 µl each) will be applied to Guthrie cards, Ahlstrom 226 filter paper, PerkinElmer 226 Five-Spot Card (PerkinElmer Health Sciences, Greenville, USA) to form dried blood spots (DBSs). The sample must be taken before transfusion therapy (or blood is taken no earlier than 48-72 hours after the transfusion) or extracorporeal membrane oxygenation. Samples will be dried for 4 hours at room temperature and then stored at 4°C in individually labeled zippered plastic bags with desiccants or other sealed containers.

DIAGNOSTIC_TEST

Obtaining Dry Blood Spots From High-risk childrens (Aged 8 Days- 7 years)

Blood samples will be taken from high-risk childrens no earlier than 3 hours after feeding by heel prick with a heel stick. Five drops of whole blood (\~75 µl each) will be applied to Guthrie cards, Ahlstrom 226 filter paper, PerkinElmer 226 Five-Spot Card (PerkinElmer Health Sciences, Greenville, USA) to form dried blood spots (DBSs). The sample must be taken before transfusion therapy (or blood is taken no earlier than 48-72 hours after the transfusion) or extracorporeal membrane oxygenation. Samples will be dried for 4 hours at room temperature and then stored at 4°C in individually labeled zippered plastic bags with desiccants or other sealed containers

DIAGNOSTIC_TEST

Obtaining Dry Blood Spots From High-risk childrens (Aged 8 - 18 years)

Blood samples will be taken from high-risk childrens no earlier than 3 hours after feeding by heel prick with a heel stick. Five drops of whole blood (\~75 µl each) will be applied to Guthrie cards, Ahlstrom 226 filter paper, PerkinElmer 226 Five-Spot Card (PerkinElmer Health Sciences, Greenville, USA) to form dried blood spots (DBSs). The sample must be taken before transfusion therapy (or blood is taken no earlier than 48-72 hours after the transfusion) or extracorporeal membrane oxygenation. Samples will be dried for 4 hours at room temperature and then stored at 4°C in individually labeled zippered plastic bags with desiccants or other sealed containers

Sponsors & Collaborators

• West Kazakhstan Medical University

  lead OTHER

Principal Investigators

• Gulmira M. Zharmakhanova, MD, PhD · West Kazakhstan Medical University

• Lyazzat M. Syrlybayeva, MD · West Kazakhstan Medical University

• Victoria I. Kononets, MD, MS · West Kazakhstan Medical University

Eligibility

Min Age

1 Day

Max Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-10-03

Primary Completion

2024-12-31

Completion

2024-12-31

Countries

• Kazakhstan

Study Locations