Inborn errors of metabolism: Historical perspectives to contemporary management.

There are many different genetic diseases called inborn errors of metabolism (IEM) which result from defective enzymes in the metabolic pathway. As a result, these defects either cause a harmful accumulation of substances or lead to a lack of certain types of molecule. The present review traces the origin and development of IEMs from Sir Archibald Garrod's theory in the early 20th century to current diagnostic and therapeutic approaches. It also involves a systematic literature review complying with PRISMA which included studies sourced from PubMed, Scopus, Web of Science and Google Scholar. It points out that high rates of consanguinity are associated with high prevalence rates for IEMs especially in the Eastern Mediterranean area. IEMS are classified as energy deficiency disorders, intoxication disorders, and storage disorders. Each category has a variety of clinical manifestations. This study incorporates different diagnostic methods ranging from simple biochemical tests to tandem mass spectrometry and next generation sequencing; while management approaches such as dietary modifications, enzyme replacement therapy and gene therapy were assessed for their efficacy. Specific attention is paid to Pakistan where there exists considerable consanguinity among people coupled with inadequate health care services which have seriously affected delivery of health care services thereby leading to numerous challenges for the country healthcare system during service provision.

Exploring WNT2 polymorphisms in comitant strabismus: A genetic association study.

BACKGROUND: Strabismus is a complex oculomotor condition characterized by a misalignment of the visual axis. The genetics of strabismus are poorly defined although a few candidate genes have been identified, among which is the WNT2 gene. Our study was designed to assess the association of single nucleotide polymorphisms (SNPs) of WNT2 in Pakistani strabismus patients. METHODS: A total of six SNPs, three intronic and three in the 3́ untranslated region, were screened in the current study. Logistic regression was performed using a dominant, recessive and additive model to determine the association of SNPs with strabismus and its clinical subtypes: esotropia and exotropia. Furthermore, haplotype analysis was performed. RESULTS: Regression analysis revealed an association of rs2896218, rs3779550, rs2285544 and rs4730775 with strabismus under the dominant model. When analyzed separately, rs2896218 and rs2285544 were found to be associated with both esotropia and exotropia, while rs4730775 was significantly associated only with exotropia under the dominant model. Based on clinical parameters, rs2896218, rs2285544 and rs4730775 were also found to be associated with the group of strabismus patients who were diagnosed at birth, but not in the group of patients who were diagnosed later in life. Haplotype analysis revealed that the haplotype A T T (corresponding to rs2896218, rs3779550 and rs2285544) was significantly more prevalent in the strabismus group. CONCLUSION: Overall, the results of the present study suggest an association of WNT2 polymorphisms with strabismus and its subtypes in the Pakistani population, though further studies are needed to elucidate their role in strabismus etiology.