Selective newborn screening of inborn errors of amino acids, organic acids and fatty acids metabolism in the Kingdom of Bahrain

Highlights

• In the Middle East high incidences of inborn errors of metabolism is suggested.

• In this study high incidence of inborn errors of metabolism is reported in Bahrain.

• Contribution of consanguinity in inherited metabolic disorders is reported.

• Mandatory screening for inborn errors of metabolism is recommended in Bahrain.

Abstract

Mandatory newborn screening for metabolic disorders has not been implemented in most Middle Eastern countries. Early detection and treatment of inborn errors of metabolism can reduce mortality and minimize morbidity. Preliminary studies conducted in some parts of Middle East suggest that the incidences of inborn errors of metabolism are reported to be higher in the region than anywhere else in the world due to the consanguinity.

In this study the incidence of inborn errors of amino acids, organic acids and fatty acids oxidation disorders was investigated from the results of blood spot analysis of 1986 symptomatic children from 1st January 2008 to 31st of December 2011. Out of 1986 newborns screened 25 infants were diagnosed and confirmed with amino acids (n = 11), organic acids (n = 9) and fatty acids oxidation (n = 5) disorders. Overall incidences based on number of live birth between 2008 and 2011 inclusive were 1:6000, 1:8000 and 1:14,000 for amino acids, organic acids and fatty acids oxidation disorders; respectively. Out of 25 infants diagnosed, 21 were the children of first cousin marriages. Results from this study suggest high incidence of inborn errors of amino acids, organic acids and fatty acids oxidation metabolism in Bahrain and significant contribution of consanguinity in inherited metabolic disorders. Mandatory screening for inborn errors of metabolism in Bahrain is highly recommended.

Introduction

Inborn errors of metabolism consist of a large class of genetic diseases involving disorders of metabolism that could lead to serious clinical consequences for affected neonates or young infants. These metabolic disorders are individually rare but collectively numerous, causing substantial morbidity and mortality [1], [2], [3]. Late diagnosis and treatment of these metabolic disorders can cause irreversible mental retardation ranging from mild to severe, neurological damage, physical disability and even fatality [4]. Implementation of nationwide screening for newborn disorders using liquid chromatography–tandem mass spectrometry (LC-MS/MS) has been widely growing in most parts of the world [5], [6]. However, in the Middle East there is a wide variation in nationwide screening panels as most countries screen only for a few disorders based on disease prevalence, limited specialized laboratories and genetic centers and lack of newborn screening infrastructure and cost. Most countries in the Middle East tend to only focus on the detection of congenital hypothyroidism, glucose-6-phospahate dehydrogenase and hemoglobinopathies but not inborn errors of amino acids, organic acids and fatty acid oxidation disorders. Despite the establishment of number of genetic centers, implementation of mass screening newborn screening programs is still challenging in the region.

Most of the inborn errors of metabolism are recessively inherited and the incidences of these disorders are reported to be higher in the Middle East than anywhere else in the world due to the consanguinity [7], [8], [9]. It has been suggested that consanguinity could increase the risk of congenital anomalies and autosomal recessive disorders [10]. In the Middle East the consanguinity rates are as high as 40% among first cousins and up to 60% in intermarriages between relatives leading to an increased incidence of genetic disorders [11], [12], [13]. However, in Bahrain the rates of consanguinity for first cousin are about 12% and second cousin is about 8% [14]. Although in Bahrain the infant mortality rate has been declined from 20.5% in year 2000 to 10.2% in year 2011, the infant mortality rate in Bahrain is still higher than Europe (4.5%) and USA (6.0%). Although the causes of this relatively high infant mortality are not well established, according to the statistics published by the Ministry of Health in Bahrain, congenital malformations, deformations, chromosomal abnormalities and genetic disorders may contribute to the 12% of the death in babies less than 5 years old. However, this statistics do not include those children die with unknown causes because of the lack of specialized genetic laboratories to identify the cause.

For the countries where there are no mandatory newborn screening programs, selective screening could be an important diagnostic tool for diagnosis of inborn errors of metabolism [15]. In this study we report the estimated incidences of inborn errors of amino acids, organic acids and fatty acids metabolism in suspected children referred for screening in a newly established Princess Al-Jawhara Centre for Genetic Diagnosis and Research in the Kingdom of Bahrain.