Variants in more than 271 different genes have been linked to hereditary retinal diseases, making comprehensive genomic approaches mandatory for accurate diagnosis. We explored the genetic landscape of retinal disorders in consanguineous families from North-Western Pakistan, harboring a population of approximately 35 million inhabitants that remains relatively isolated and highly inbred (~50% consanguinity). We leveraged on the high degree of consanguinity by applying genome-wide high-density single-nucleotide polymorphism (SNP) genotyping followed by targeted Sanger sequencing of candidate gene(s) lying inside autozygous intervals. In addition, we performed whole-exome sequencing (WES) on at least one proband per family. We identified 7 known and 4 novel variants in a total of 10 genes (ABCA4, BBS2, CNGA1, CNGA3, CNGB3, MKKS, NMNAT1, PDE6B, RPE65, and TULP1) previously known to cause inherited retinal diseases. In spite of all families being consanguineous, compound heterozygosity was detected in one family. All homozygous pathogenic variants resided in autozygous intervals ≥2.0 Mb in size. Putative founder variants were observed in the ABCA4 (NM_000350.2:c.214G>A; p.Gly72Arg; ten families) and NMNAT1 genes (NM_022787.3:c.25G>A; p.Val9Met; two families). We conclude that geographic isolation and sociocultural tradition of intrafamilial mating in North-Western Pakistan favor both the clinical manifestation of rare “generic” variants and the prevalence of founder mutations.

Background: Inherited retinal degenerations (IRDs) are a group of rare genetic conditions affecting retina of the eye that range in prevalence from 1 in 2000 to 1 in 4000 people globally. This review is based on a retrospective analysis of research articles reporting IRDs associated genetic findings in Pakistani families between 1999 and April 2023. Methods: Articles were retrieved through survey of online sources, notably, PubMed, Google Scholar, and Web of Science. Following a stringent selection criterion, a total of 126 research articles and conference abstracts were considered. All reported variants were cross-checked and validated for their correct genomic nomenclature using different online resources/databases, and their pathogenicity scores were explained as per ACMG guidelines. Results: A total of 277 unique sequence variants in 87 distinct genes, previously known to cause IRDs, were uncovered. In around 70% cases, parents of the index patient were consanguineously married, and approximately 88.81% of the detected variants were found in a homozygous state. Overall, more than 95% of the IRDs cases were recessively inherited. Missense variants were predominant (41.88%), followed by Indels/frameshift (26.35%), nonsense (19.13%), splice site (12.27%) and synonymous change (0.36%). Non-syndromic IRDs were significantly higher than syndromic IRDs (77.32% vs. 22.68%). Retinitis pigmentosa (RP) was the most frequently observed IRD followed by Leber’s congenital amaurosis (LCA). Altogether, mutations in PDE6A gene was the leading cause of IRDs in Pakistani families followed by mutations in TULP1 gene. Conclusion: In summary, Pakistani families are notable in expressing recessively inherited monogenic disorders including IRDs likely due to the highest prevalence of consanguinity in the country that leads to expression of rare pathogenic variants in homozygous state.

Background: Pyruvate kinase deficiency is an exceptionally rare autosomal recessive Mendelian disorder caused by bi-allelic pathogenic variants in the PKLR gene. It is mainly characterized by chronic nonspherocytic hemolytic anemia though other symptoms such as splenomegaly, hepatomegaly, pallor, fatigue, iron overload, shortness of breath, hyperbilirubinemia, and gallstones might also prevail. Case presentation: We present here a novel genetic defect in the PKLR gene that correlates with pyruvate kinase deficiency phenotype in a consanguineous family from North-Western Pakistan. The family included three affected individuals who were all born to consanguineous parents. The proband, a 13-year-old female of Pashtun ethnicity, showed chronic nonautoimmune hemolytic anemia since birth, extremely low hemoglobin (7.6 g/dL) and pyruvate kinase (12.4 U/g Hb) levels, splenomegaly, and hepatomegaly. Bone marrow aspirate showed a markedly decreased myeloid to erythroid ratio and hypercellular marrow particles due to hyperplasia of the erythroid elements. Molecular characterization of the proband’s genomic DNA uncovered a likely pathogenic homozygous missense variant p.[D339N] in exon 7 of the PKLR gene. In-depth in silico analysis and familial cosegregation implies p.[D339N] as the likely cause of pyruvate kinase deficiency in this family. Further in vitro or in vivo studies are required to validate the impact of p.[D339N] on protein structure and/or stability, and to determine its role in the disease pathophysiology. Conclusions: In summary, these findings suggest a novel genetic defect in the PKLR gene as a likely cause of pyruvate kinase deficiency, thus further expanding the mutational landscape of this rare Mendelian disorder.

Background: Malnutrition is a major public health problem and is directly associated with poor infant and young child feeding (IYCF) practices. The study aimed to identify the inadequacies in the feeding practices for children aged 0-23 months through a cross-sectional KAP survey. Methods: Data was collected on demographic indicators, IYCF practices, 24 hours dietary recall, childhood illnesses and anthropometrics and compared with WHO guidelines. Results: Only 44.8% mothers timely initiated breastfeeding, 57% fed colostrum and 32.9% practiced exclusive breastfeeding. Only 63.2% children were breastfed beyond first year and 42.2% up to second year. Nearly half of the children were introduced to complementary feeding at 6-8 months. Minimum meal frequency (MMF) was offered to 57.5%, minimum dietary diversity (MDD) to 53.2% and minimum acceptable diet (MAD) to 37.1%. Prevalence of childhood illnesses was high. Prevalence of stunting, wasting and underweight was 19.1%, 4% and 11.4%, respectively. Mother’s working status was positively associated with timely initiation of breastfeeding (OR 1.82; 95% CI 1.17, 2.83) and MDD (OR 1.53; 95% CI 0.93, 2.51) but inversely associated with exclusive breastfeeding (OR 0.52; 95% CI 0.16, 1.66). Colostrum was given by mothers with better socioeconomic status (OR 1.3; 95% CI 0.84, 2.04) and higher education level (OR 1.22; 95% CI 0.71, 2.08). Socioeconomic status directly affected MDD (OR 2.32; 95% CI 1.40, 3.83) and MAD (OR 1.51; 95% CI 0.90, 2.54). The health status of children was positively impacted by exclusive breastfeeding (OR 2.33; 95% CI 0.89, 6.14), timely introduction of complementary feeding (OR 1.39; 95% CI 0.86, 2.26), MMF (OR 1.38; 95% CI 0.82, 2.32) and MAD (OR 1.30, 95% CI 0.77, 2.20) and negatively impacted by bottle feeding (OR 0.79; 95% CI 0.50, 1.27). Conclusions: The mothers showed moderate to low compliance to WHO IYCF indicators despite high educational status. The inadequacies in IYCF practices demand for immediate awareness interventions.

Cutaneous Leishmaniasis (CL), the most prevalent type of Leishmaniasis, is a significant public health problem in various regions of the world including Pakistan, resulting in huge morbidity and social stigmatization. This retrospective study was carried out mainly in three districts: Bajaur, Malakand and Dir Lower of Khyber Pakhtunkhwa (KP), Pakistan. Additionally, some cases from other districts were also recorded. Patients of different localities and age groups visiting healthcare centers including District Headquarters Hospitals in Dargai, Malakand and Bajaur were included in the study, with the approval from District Health Officer (DHO) of concerned districts. In total, 2035 cases of CL were recorded during the study period from January 2022 to February 2023. Statistical analysis revealed that the disease predominantly affected patients under 20 years of age (n = 1259, 61.9%), particularly males (n = 1067, 52.5%). The proportion of facial lesions was predominant (n = 1145, 56.3%), followed by lesions on the upper extremities (n = 317, 15.6%) and lower extremities (n = 338, 16.6%). Our findings indicate a high prevalence of CL in district Bajaur (n = 1222, 60.04%), followed by Malakand (n = 587, 28.84%) and Dir Lower (n = 153, 7.52%). Peak cases were recorded during summer and spring whereas autumn and winter showed a relatively lower incidence of CL, likely due to harsh environmental conditions that reduce the survival of sandflies.

Refugees have a basic right to good health care, and countries of destination have a responsibility to offer medical care. Timely diagnosis and rehabilitation by counselling were recommended for improved mental health outcomes. This survey on Psychological Well-Being of Afghan refugees in Pakistan remains pertinent to the need for global mental health care for refugees. This study is the initial attempt to assess the predictors of psychological well-being among Afghan Refugees in Pakistan. The research is designed as a quantitative cross sectional survey. Multi-stage technique of sampling is used to assemble information with a sample size of 1185. Low psychological well-being is reported by 43% of the Afghan refugees by World health organization wellbeing V. The establishment of mental health screening units at border entry points and in refugee hosting regions seems essential for early diagnosis and effective referral system.