Abstract
Inborn errors of metabolism (IEMs) are rare group of genetic disorders comprising of more than 1,000 different types. Around 200 of IEMs are potentially treatable through diet, pharmacological and other therapies, if diagnosed earlier in life. IEMs can be diagnosed early through newborn screening (NBS) programs, which are in place in most of the developed countries. However, establishing a NBS in a developing country is a challenging task due to scarcity of disease related data, large population size, poor economy, and burden of other common disorders. Since, not enough data is available for the prevalence of IEMs in Pakistan; therefore, in this study, we set out to find the prevalence of various treatable IEMs in a cohort of intellectually disabled patients suspected for IEMs, which will help us to initiate a NBS program for the most frequent IEMs in Pakistan. Therefore, a total of 429 intellectually disabled (IQ <70) patient samples were collected from Pakistan. A subset of 113 patient samples was selected based on the clinical information for the detailed biochemical screening. Advance analytical techniques like, Amino Acid Analyzer, GC-MS, UHPLC-MS, and MS/MS were used to screen for different treatable IEMs like aminoacidopathies, fatty acid β-oxidation disorders and mucopolysaccharidoses (MPS) etc. A total of 14 patients were diagnosed with an IEM i.e., 9 with homocystinuria, 2 with MPS, 2 with Guanidinoacetate methyltransferase (GAMT) deficiency and 1 with sitosterolemia. These IEMs are found frequent in the collected patient samples from Pakistan. Thus, present study can help to take an initiative step to start a NBS program in Pakistan, especially for the homocystinuria having highest incidence among aminoacidopathies in the studied patients, and which is amenable to treatment. This endeavor will pave the way for a healthier life of affected patients and will lessen the burden on their families and society.
Highlights
Inborn errors of metabolism (IEMs) are phenotypically and genetically heterogeneous disorders which are caused by the deficiency of a protein that results in the accumulation of intermediary metabolites which cannot be processed further
Diet and pharmacological therapies are available for the treatment of several IEMS
More comprehensive large scale studies covering all areas of Pakistan would be required to know the real prevalence of IEMs
Summary
Inborn errors of metabolism (IEMs) are phenotypically and genetically heterogeneous disorders which are caused by the deficiency of a protein (most often an enzyme or a transporter) that results in the accumulation of intermediary metabolites which cannot be processed further. Up till more than 1,000 IEMs have been reported and about 200 of such disorders are potentially treatable when diagnosed before the appearance of clinical symptoms [5,6,7]. Affected individuals usually appear normal at the time of birth, but symptoms (e.g., poor feeding, seizures, lethargy etc.) may develop within hours to weeks depending upon the disease severity. If diagnosed earlier, it allows treatment at the pre-symptomatic stage, preventing the subsequent development of intellectual disability. Diagnosis of these disorders can be performed through newborn screening (NBS) programs, which have been established in many developed countries [7,8,9]
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