Unveiling the hidden burden: challenges and spectrum of inborn errors of metabolism in LMICs.

Abstract

Inborn Errors of Metabolism (IEM) are an important cause of morbidity and mortality in neonates and children, particularly in resource-limited settings. In Pakistan, comprehensive data on IEMs remain scarce, contributing to underdiagnosis and delayed interventions. This retrospective study reviewed medical records of children presenting with suspected IEMs to a tertiary care hospital in Islamabad between January 2014 and May 2019. Cases were identified through medical record coding, and diagnoses were based on biochemical tests and enzyme assays. A total of 64 patients were identified. Diagnoses included glycogen storage disorders (n = 15), galactosemia (n = 3), Gaucher's disease (n = 3), mucopolysaccharidosis (n = 4), congenital adrenal hyperplasia (n = 19), and unspecified IEMs (n = 20). One case was initially misdiagnosed as drug overdose, while six cases lacked sufficient data for classification. Delayed diagnosis, limited availability of genetic testing, and financial constraints resulted in predominantly symptomatic management. Outcomes were poor, with many patients succumbing during care. This study highlights the urgent need for improved diagnostic capacity for IEMs in Pakistan. The establishment of genetic testing facilities, including whole-exome sequencing and a cost-effective IEM gene panel, is critical to enable timely and accurate diagnosis, improve clinical management, and ultimately reduce morbidity and mortality in affected children. The study highlights the significant burden of Inborn Errors of Metabolism (IEM) in a low-middle-income country, emphasizing the challenges of late diagnosis, lack of genetic diagnostic tools, and poor follow-up due to financial constraints. This study adds critical insights into the prevalence, spectrum, and clinical outcomes of IEMs in Pakistan. It identifies specific gaps in diagnostic infrastructure, management practices, and healthcare accessibility in resource-limited settings. The study emphasizes the importance of addressing diagnostic and financial barriers to reduce the morbidity and mortality associated with IEMs in Pakistan.