History Of Consanguineous Marriage Research Articles

NEURAL TUBE CLOSURE ANOMALIES: EPIDEMIOLOGICAL STUDIES AND RISK FACTORS AT THE NEONATAL AND NEONATAL RESUSCITATION DEPARTMENT OF MOHAMMED VI UNIVERSITY HOSPITAL, OUJDA

Objective:This studyaims to identify the sociodemographic, maternal, and obstetricriskfactorsassociatedwith neural tube defects (NTDs) and determinetheirprevalenceamongnewbornshospitalized in the neonatology and neonatal intensive care unit at CHU Mohamed VI Oujda. Methods:Weconducted a descriptive retrospectivestudy over an 18-month period, including all newbornshospitalizedwithisolated or associatedNTDs. Incomplete records wereexcludedfrom the analysis. Results:Out of 797 hospitalizednewborns, 66 hadcongenital malformations, including 10 cases of NTDs (1.25%). The types of NTDsidentifiedwereanencephaly (1 case), spina bifida (6 cases), and encephalocele (3 cases). The majority of mothers had an average age of 34.3 years, with 80% coming from a low socioeconomic status and 60% having a history of consanguineous marriages. Additionally, fenugreek consumption during the first trimester of pregnancy was reported in 70% of cases, while only 20% of mothers had taken folic acid.Regarding the newborns, 70% presented with hypotonia, and 60% exhibited weak or absent primitive reflexes. The short-term postoperative mortality rate was 30%. Discussion:The prevalence of neural tube defects (NTDs) observed in this study is significantly higher than the global average, which may be explained by unfavorable socioeconomic conditions and maternal nutritional deficiencies. Fenugreek consumption and low folic acid supplementation were identified as significant risk factors. Conclusion:To reduce the incidence of NTDs, itis essential to Strengthening prenatal care, encouraging folic acid supplementation, and advising against the consumption of fenugreek during pregnancy are essential. A preventive strategy tailored to local specificities could significantly improve newborn health and reduce complications associated with neural tube defects (NTDs).

Familial Hemophagocytic Lymphohistiocytosis Screening in Neonatal Sepsis.

Neonatal sepsis and familial hemophagocytic lymphohistiocytosis (fHLH) have similar clinical and laboratory symptoms and the possibility of overlooking fHLH diagnosis is high in newborns with sepsis. History of consanguineous marriage and/or sibling death, hepatomegaly/splenomegaly, and hyperferritinemia (>500ng/mL) are likely to support fHLH in newborns with sepsis. Therefore, in newborns with sepsis in whom at least 2 of these 3 criteria were detected, genetic variants was investigated for the definitive diagnosed of fHLH. According to the results of genetic examination, we investigated whether these criteria supporting fHLH could be used as a screening test in fHLH. fHLH-associated genetic variants were investigated in 22 patients diagnosed with neonatal sepsis who fulfilled at least 2 of the following criteria (1) history of consanguineous marriage and/or sibling death, (2) hepatomegaly/splenomegaly, and (3) hyperferritinemia (>500ng/mL). Heterozygous variants were determined in 6 patients (27.2%): 3 STXBP2 , 1 STX11 , 1 UNC13D , and 1 PRF1 . Polymorphisms associated with the clinical symptoms and signs of HLH were determined in 5 patients (22.7%): 4 UNC13D , 1 PRF1 . Two patients were in the heterozygous variants and polymorphism associated with the clinical symptoms and signs of HLH groups. In 12 patients, benign polymorphisms were detected in STXBP2 and UNC13D genes. No change in fHLH associated genes were found in 1 patient. Some variants and/or polymorphisms identified in our patients have been previously reported in patients with HLH. Therefore, we recommend further investigation of fHLH in patients with neonatal sepsis who fulfill at least 2 of the above 3 criteria.

Application of whole exome sequencing in carrier screening for high-risk families without probands.

This study aimed to screen the genetic etiology for the high-risk families including those with an adverse pregnancy history, a history of consanguineous marriages, or a history of genetic diseases, but lack of proband via whole exome sequencing (WES). 128 individuals from high-risk family were tested by WES. The candidate variants were analyzed according to the ACMG criteria to screen the potential carriers. At-risk couples (ARCs) who harbored the same causative gene were provided with precise fertility guidance to avoid the birth of children with birth defects. The total detection rate was 36.72%, with pathogenic/likely pathogenic (P/LP) variants found in 47 individuals, and variants of uncertain significance (VUS) were found in 34. Among couples with adverse pregnancy history: P/LP variants were found in 38 individuals, and VUS were found in 26, for a detection rate of 34.55%; among members of family history of genetic disease or consanguineous marriages: P/LP variants were found in nine individuals, and VUS were found in 8, for a detection rate of 50.00%. Otherwise, we detected 19 ARCs who both carried P/LP variants in the same gene, with a theoretical offspring prevalence of up to 7.42%. In the absence of probands, carrier screening using WES can provide an efficient tool for screening the molecular etiology of high-risk families.

The Impact of Consanguinity on Severity of Posterior Urethral Valve

Background: Posterior urethral valve (PUV) is one of the frequent causes of obstructive uropathies at birth. When inadequately managed, it leads to vesicoureteric reflux disease, recurrence of UTIs, voiding disorder and chronic renal insufficiency. These valves have been observed among the siblings, twin children and also in the subsequent generation. However, their occurrence rate and association with consanguineous have never been investigated. Objective: To assess the frequency and impact of kinship on the severity of the posterior urethral valve at our centre. Study Design: A Retrospective Study Place and duration of study: Diagnosed cases of posterior urethral valves who underwent valve fulguration from Jan 2012 to April 2020 were assessed in this study, conducted at Shifa International Hospital, Islamabad. Material and method: Patients were diagnosed via voiding symptoms, ultrasound, and confirmation by VCUG and cystoscopy. In all patients, the history of consanguineous marriage and any history of PUV in the family was inquired. All cases were evaluated for renal function with BUN and creatinine, including eGFR, as per Schwartz's formula. A nuclear scan was performed in all patients to rule out renal scaring and split renal function. Results: The mean age of children who underwent valve fulguration was 4.34 + 2.7 years. Family history of first-degree cousin marriage was found in 56 (33.0%) patients. Statistical analysis of clinical parameters of the posterior urethral valve, including the degree of hydronephrosis, vesicoureteric reflux and chronic kidney disease, showed that the product of cousin marriage had more severe disease. Conclusion: One-third of PUV patients had a history of consanguineous marriages in this study. These cases develop early renal insufficiency as well as a more severe disease. Keywords: Posterior urethral valve, Consanguinity, Severity, Renal insufficiency, Retrospective Study

A fatal case of Harlequin ichthyosis: Experience from low-resource setting.

Harlequin ichthyosis is a severe and fatal presentation of ichthyosis with an autosomal recessive inheritance. Infants with Harlequin ichthyosis have a high mortality rate, and a dismal prognosis; therefore the majority of neonates die shortly after birth from infection, heat loss, dehydration, electrolytic imbalances, or respiratory distress. The aim of this case report was to present a fatal case of Harlequin ichthyosis with no family history of any inherited skin disorder. A 3-day-old baby was presented to the emergency room with congenital abnormalities at birth, fissured hyperkeratotic skin, and thick yellow plates of scales. The parents had no history of consanguineous marriage, no relevant past medical history, and no family history of the same condition. The patient was unwell, pulse 162 times/minute, respiratory rate 48 times/minute, and axillary temperature 36.9oC. APGAR score was 8 in the 1st minute and 9 in the 5th minute. Based on the typical clinical appearance, the patient was diagnosed with Harlequin ichthyosis. Due to a lack of facility, a mutation analysis was not carried out. The patient was then transferred to the neonatal intensive care unit (NICU) and treated in a humidified incubator and medicated with intravenous antibiotics (ampicillin sulbactam 125 mg/12 hour and gentamicin 13 mg/24 hour), topically fusidic acid and mild emollients. A central venous catheter was used for intravenous access. The poor prognosis resulted in the patient dying at the age of 5-day-old. This case highlights that prenatal diagnosis is critical for early detection and disease prevention. Mutation screening for the ABCA12 gene is suggested for consanguinity marriages and with a history of ichthyosis.

Bilateral Involvement in Developmental Dislocation of the Hip: Analysis of 561 Patients Operated on Using the Limited Posteromedial Approach.

Our objective was to scrutinize the risk factors related to bilateral involvement in the developmental dysplasia of the hip (DDH) and to inspect the impact of bilaterality on the enduring results of the DDH. All patients, aged between 6 and 18 months, who underwent surgery using the limited posteromedial approach (734 hips from 561 patients), were included in this study. The number of births, birth type, history of consanguineous marriage, family history, and swaddling were analyzed. Physical examination and complaints of the patients were evaluated, and direct radiographs were examined in terms of the redislocation, avascular necrosis, and residual acetabular dysplasia. Among the 561 patients, bilateral DDH was observed in 173 patients (30.8%). The use of swaddling was found to be statistically significant between groups (p = 0.012). The use of swaddling for more than one month was associated with a higher odds ratio for bilaterality (p = 0.001, OR = 1.56, 95% CI: 1.2-2.0). Furthermore, bilaterality was associated with a higher risk for redislocation in DDH (p = 0.001, OR = 4.25, 95% CI: 1.6-11.2). The study concludes that swaddling for over a month is strongly linked with the bilateral involvement in DDH. It is important to note that bilaterality plays a crucial role in the development of redislocation after open reduction in DDH.

Evaluation of Risk Factors in Patients with Primary Open Angle Glaucoma and Ocular Hypertension

Objective: The purpose of our study was to compare the age, gender, intraocular pressure (IOP), central corneal thickness (CCT), spherical equivalent values, smoking, family history of glaucoma and additional systemic diseases in patients with primary open angle glaucoma (POAG) and patients with ocular hypertension (OHT); and to evaluate the relationships of these factors with each other. Material Methods: 40 patients with POAG, 40 patients with OHT and 40 individuals as control group were included in the study. Age, gender, IOP, CCT, spherical equivalent values, family history of glaucoma, history of consanguineous marriage, smoking, systemic diseases of each subject were recorded. Results: There was no significant difference in gender and average age between the groups (p=0.238 and p=0.51, respectively). IOP values was higher in POAG and OHT groups compared with the control group (p=0.000). CCT was higher in OHT group compared with the other groups (on the right, p=0.001 and p=0.008, respectively; on the left, p=0.013 and p=0.006, respectively). There was no significant correlation between IOP and CCT values. There was no significant difference in mean spherical equivalent values (on the right eye p=0.686; on the left eye p=0.640) . The incidence of diabetes mellitus, hypertension, hyperlipidemia and coronary artery disease was the similar in all groups (p=0.417, p=0.058, p=0.79, p=0.236, respectively). Family history of glaucoma is increased in POAG and OHT group compared with the control group (p=0.000). There was no significant difference in history of consanguineous marriage, smoking and alcohol consumption status among all groups (p=0.899, p=0.492, p=0,899, respectively). Conclusion: High IOP is the most important risk factor in the POAG and OHT groups. Individuals with OHT and thin CCT are at higher risk of developing POAG. The significant presence of a familial history of glaucoma in the POAG and OHT groups indicates that genetic factors could be a significant risk factor. Diabetes, hypertension, and high myopia are factors that increase the risk of glaucoma.

Study of the epidemiologic characteristics of childhood vitiligo in Egyptian children

Background Vitiligo during childhood is common. Pediatric vitiligo has a profound effect on the quality of life of both children and their parents. Aims and objectives To investigate the epidemiologic characteristics of vitiligo among Egyptian children. Patients and methods A cross-sectional study was conducted and included children of both sexes from birth to less than 18 years of age. The study included schools and maternity and childhood care centers in Sohag Governorate, Upper Egypt, during the period from March 2019 to February 2020. Complete demographic and clinical information of children with vitiligo were recorded. Dermatological examination of patients with vitiligo was done. Vitiligo area and severity index of patients was calculated. Results Of 2594 screened children, 18 (0.7%) had vitiligo. The median age of children with vitiligo was 12 (2–17) years. The age interval from 13 to less than 18 years accounted for 44.4% of vitiligo cases. Females cases of vitiligo were more prevalent (61.1%). Overall, 72.2% of patients with vitiligo were resident of rural areas. Of the 18 cases with childhood vitiligo, 83.3% of cases had a history of consanguineous marriage and 66.5% had vitiligo vulgaris. A proportion of cases related the exacerbation of the disease to exposure to psychological stress. Conclusions Childhood vitiligo was detected in 0.7% of pediatric population in Upper Egypt. The majority of cases with childhood vitiligo had a history a consanguineous marriage between the parents. Psychic trauma was identified as a potential exacerbating factor of childhood vitiligo.

Cross-Sectional Study to Estimate the Prevalence of Inner-Ear Anomalies in Children With Congenital Sensorineural Hearing Loss by High-Resolution Computed Tomography (HRCT) Temporal Bone Scan.

Background Congenital sensorineural hearing loss (SNHL) is one of the most common birth defects with an incidence ratio of 1:1000 live births in India. Imaging plays an important role in the evaluation of congenital SNHL. As there is a paucity of studies in the Indian setting to determine the prevalence of inner-ear abnormalities, this study attempts to throw light on the various inner-ear anomalies that are prevalent in our setup in the Northern part of Karnataka using high-resolution computed tomography (HRCT) temporal bone scan. Objectives The objectives of this study are estimation of the prevalence of inner-ear anomalies in children with congenital SNHL by employing a radiologic assessment of HRCT temporal bone scans and determination of the factors associated with the identification of these abnormalities like demographic factors and degree of hearing loss. Methods Children with congenital SNHL underwent clinical evaluation with history takingand general and ear examination. Otoacoustic emission(OAE) and brainstem evoked response audiometry (BERA) measurements were obtained. A radiological assessment by HRCT temporal bone scan was done. Using the classification criteria of inner-ear malformations by Jackler and Sennaroglu as a reference, diagnostic standards were established in studying inner-ear malformations. Data were collected and entered in a Performa, which includes patient's demography, audiological findings, and radiological findings, and the results were analyzed. Data were entered into Microsoft Excel, and statistical analysis was carried out using IBMSPSSStatistics for Windows, Version 27 (Released 2020; IBM Corp., Armonk, New York, United States). Categorical variables were presented as frequency and percentage. Then the prevalence of inner-ear anomaly was estimated. Correlation between inner-ear anomaly and other factors was calculated using the Chi-square test. Results The prevalence of inner-ear anomalies identified in congenital SNHL by HRCT scan was as follows: 26.08% (12/46), 26.1% (24/92) of inner ears was anomalous, 23.9% of the cochlea was anomalous, 6.5% of the vestibule was anomalous, 5.4% of the vestibular aqueduct was anomalous, and 3.2% of the semicircular canal was anomalous. Cochlear aplasia, incomplete partition, common cavity, and cochlear hypoplasia were the anomalies found. Few cochleas had an abnormal cochlear height, though they appeared normal structurally. The dilated vestibule was the most common vestibular abnormality. There was a negative association found between the inner-ear anomaly in children with congenital SNHL who had a history of consanguineous marriage in their parents. Conclusion High-resolution temporal CT scanning could provide detailed information on the pathology of the inner ear in congenital SNHL, which can help in better planning the surgery for cochlear implantation and understanding the prognosis.

Novel mutations and molecular pathways identified in patients with brain iron accumulation disorders.

Brain iron accumulation disorders (BIADs) are a group of diseases characterized by iron overload in deep gray matter nuclei, which is a common feature of neurodegenerative diseases. Although genetic factors have been reported to be one of the etiologies, much more details about the genetic background and molecular mechanism of BIADs remain unclear. This study aimed to illustrate the genetic characteristics of BIADs and clarify their molecular mechanisms. A total of 84 patients with BIADs were recruited from April 2018 to October 2022 at Xuanwu Hospital. Clinical characteristics including family history, consanguineous marriage history, and age at onset (AAO) were collected and assessed by two senior neurologists. Neuroimaging data were conducted for all the patients, including cranial magnetic resonance imaging (MRI) and susceptibility-weighted imaging (SWI). Whole-exome sequencing (WES) and capillary electrophoresis for detecting sequence mutation and trinucleotide repeat expansion, respectively, were conducted on all patients and part of their parents (whose samples were available). Variant pathogenicity was assessed according to the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP). The NBIA and NBIA-like genes with mutations were included for bioinformatic analysis, using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genome (KEGG). GO annotation and KEGG pathway analysis were performed on Metascape platform. In the 84 patients, 30 (35.7%) were found to carry mutations, among which 20 carried non-dynamic mutations (missense, stop-gained, frameshift, inframe, and exonic deletion) and 10 carried repeat expansion mutations. Compared with sporadic cases, familial cases had more genetic variants (non-dynamic mutation: P=0.025, dynamic mutation: P=0.003). AAO was 27.85±10.42 years in cases with non-dynamic mutations, which was significantly younger than those without mutations (43.13±17.17, t=3.724, P<0.001) and those with repeated expansions (45.40±8.90, t=4.550, P<0.001). Bioinformatic analysis suggested that genes in lipid metabolism, autophagy, mitochondria regulation, and ferroptosis pathways are more likely to be involved in the pathogenesis of BIADs. This study broadens the genetic spectrum of BIADs and has important implications in genetic counselling and clinical diagnosis. Patients diagnosed as BIADs with early AAO and family history are more likely to carry mutations. Bioinformatic analysis provides new insights into the molecular pathogenesis of BIADs, which may shed lights on the therapeutic strategy for neurodegenerative diseases.

Novel homozygous ADAMTS17 missense variant in Weill-Marchesani syndrome.

To explore the phenotype and genotype of Weill-Marchesani syndrome (WMS) in a Chinese family and review related literature. Three WMS patients and other unaffected individuals in this family with a history of consanguineous marriage were included in this study. Medical history, comprehensive ophthalmic examinations, and systemic evaluation, as well as whole exome and Sanger sequencing of specific genomic regions, were performed. The three affected siblings presented with short stature, brachydactyly and ocular disorders, including very shallow anterior chamber, high myopia, microspherophakia lens subluxation with stretched zonules and glaucoma. Genetic analysis verified a homozygous missense mutation (c.2983C>T: p. Arg995Trp) in ADAMTS17, which was correlated with the diseases in this family, indicating an autosomal recessive inherited manner of WMS. This review aims to summarize the mutation sites of WMS genes, so as to prevent the disease and better guide clinical diagnosis and treatment. A novel homozygous missense variant of ADAMTS17 is identified in a WMS family with a history of consanguineous marriage. Our study expands the range of mutations associated with WMS and deepens our understanding of pathology in disease associated with ADAMTS17 variants.

Eruptive collagenoma: An interesting case report

Eruptive cutaneous collagenoma is a non-familial connective tissue nevi of unknown etiology presented with an abrupt onset. To date, the literatures on eruptive cutaneous collagenoma are extremely rare in India. Herein, we report a rare case of eruptive collagenoma in a 26 year old young male with epilepsy and mental retardation, who presented with multiple asymptomatic papules and nodules over the chest and abdomen with no systemic involvement. There was no positive family history or history of consanguineous marriage, and diagnosis was confirmed histologically. We report this case due to paucity in Indian literature.

Consanguineous marriages and poor pregnancy outcomes

Objective: To examine the influence of consanguineous marriage on pregnancy outcomes and highlight the factors, such as rural region residency, unemployment, and poor education. Methodology: This prospective study used a questionnaire for women in Babylon teaching hospital and some private clinics from the 1st of June 2021 to the 1st of July 2022. Randomly, 500 women were taken, 150 of them had history of consanguineous marriage. Results: Mean age of women was 30 years; 77% were rural, 4.1% were employed, 21.6% had congenital abnormalities, 8.8% experienced recurrent miscarriages, and 10.1% suffered unexplained intrauterine mortality. 350 had no history of consanguineous marriage, a mean age of 34, 46.6% resided in rural areas, 79.3% were employed, 8.2% had congenital abnormalities, 3.4% had recurrent miscarriages, and 4% experienced unexplained intrauterine mortality. Consanguinity and rural living (p=0.0001) and employment (p=0.0001) were substantially correlated. Consanguinity was correlated with congenital abnormalities (p=0.0001), recurrent miscarriage (p=0.022), and unexplained intrauterine death (p=0.036). Conclusion: Consanguineous marriage is prevalent in our region (30%), especially in rural areas and jobless groups, which increases prenatal abnormalities, miscarriage, and intrauterine mortality.

A retrospective study on clinical and epidemiological profile of nonsyndromic cleft lip and palate patients admitted in a large Comprehensive Cleft Care Centre in West Bengal, India

Aim: The aim of this study is to observe the clinical and epidemiological profile of nonsyndromic cleft lip (CL) and/or palate patients admitted to a cleft care center in West Bengal from May 2021 to April 2022. Materials and Methods: A retrospective epidemiological study had been done by preparing a master data sheet to record the patient's data from a Comprehensive Cleft Care Centre in West Bengal. The study variables included were patient's age reporting at the hospital, type of cleft, sex distribution of patients, residential address of the parents, socioeconomic status through parents' education, occupation, and monthly income, and consanguineous marriage history of the family. Results: A total of 276 nonsyndromic cleft patients during the time period (May 2021 to April 2022) were considered. Among these, 164 were male and 112 were female patients. The mean age of patients reporting to this hospital on average was 13–18 months. CL with palate patients (62%) predominated than any other type and was mostly seen in male patients (69.59%); isolated CL (22%) cases were more in females (56.25%), whereas isolated cleft palate (16%) cases were seen more in males (62.79%); unilateral (77%) and left-sided cleft (67%) were found predominantly than bilateral cases (23%) and seen mostly in females, whereas bilateral cleft cases were more in males. Most of the patients belonged to North 24 Parganas District which is an adjacent district of Kolkata, and most of the families belonged to a low socioeconomic group, and interestingly, most of them had consanguineous marriage history (61%) with at least one generation. Conclusion: The results of this study provided that CL with palate type is more common among all types of clefts and predominantly found in males than females in West Bengal. The unilateral left-sided cleft is predominant among all other varieties. Most of the parents belonged to low socioeconomic status and are having consanguineous marriage history. We need to spread awareness among the public through ads and banners, social media, and medical free camps about the deformity of CL and/or palate and also possible preventive measures, make arrangements for free treatment among the CL and/or CL and palate population for better life of cleft patients and their parents.

Twin pregnancy: Live fetus with complete hydatidiform molar—A case report

Gestational trophoblastic disease encompasses a range of lesions, each culminating in varied clinical manifestations. Among these, the simultaneous occurrence of molar changes within the placenta and a viable fetus remains a particularly elusive and challenging presentation, posing intricate dilemmas for obstetricians. In this article, we delineate a distinct case involving a 21-year-old woman with a history of consanguineous marriage. She was referred from Médecins Sans Frontières to the Rafic Hariri University Hospital during her 19th week of gestation. With an unremarkable medical history and uncomplicated previous pregnancies, her presentation to the Rafic Hariri University Hospital was punctuated by symptoms of premature labor. Clinical evaluations revealed ruptured membranes, a fetus-positioned breech, and discernible complications tied to the placental morphology. Given these clinical findings, a decision was made in favor of a Cesarean delivery. Prior to this, the patient had been administered corticosteroids and tocolytics. Subsequent delivery produced a live male infant at 34 + 5 gestational days, and further assessment unveiled a complete molar pregnancy. The coexistence of a viable fetus alongside a complete molar pregnancy is an infrequently documented phenomenon, underlining the clinical significance of this case. A comprehensive literature survey reinforced the exceptional nature of our findings. Postpartum, both the mother and neonate were monitored for a month, ensuring their well-being. This case accentuates the paramountcy of prompt and precise diagnostic interventions when faced with atypical presentations. It further underscores the imperative for obstetricians to possess nuanced expertise in confronting the intricate challenges posed by gestational trophoblastic disease, ensuring optimal maternal and neonatal outcomes.

Clinico-Hematological Profile in Hemoglobin SE Disease: A Case Series from a Tertiary Care Centre.

Hemoglobin SE (HbSE) disease are rare globally and there is paucity of literature regarding this condition. Cases reported in the Indian scenario so far have been limited to the tribal populations. This case series aims to highlight the rarity of this double heterozygous state and to raise awareness of its community prevalence beyond the tribal population. This is a case series over a 5-year observation period with six cases of double heterozygosity for HbS and HbE in our tertiary care centre. Four cases were in the 8-15years' age group and 2 cases of 24-25years' age group reported for initial evaluation due to easy fatigability and weakness: Two cases were siblings with history of consanguineous marriages in the family. Mild Pallor, variable icterus, spleen was just palpable in three of the cases and low MCV recorded in all cases. Sickling tests were positive and high performance liquid chromatography (HPLC) revealed both HbS > 50% and HbE fractions ≥ 25%. It's important to detect this rare condition, prevalent in consanguineous marriages as dreaded complications like sickling crisis may manifest during pregnancy and air travel. Detection and genetic counselling is important for prognosis, planning follow up and therapy for this uncommon double heterozygous state.

P110 AIRE gene mutation predisposing chronic mucocutaneous Candidiasis in two kids from a Chinese family

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectivesChronic mucocutaneous candidiasis (CMC) is a group of clinical syndromes characterized by chronic recurrent skin, nails, and mucosal superficial Candida infections. Various gene mutations have been reported to predispose individuals to CMC and its related syndrome. This study aims to study the clinical features and the genetic background underlying two kids of CMC from a Chinese family.MethodsClinical and laboratory findings of the two patients were studied, including physical examination, direct microscopic examination, and fungal culture. Genomic DNA of all family members was extracted from peripheral blood leukocytes, and whole-exome sequencing (WES) was performed.ResultsA 2-year-old boy and his sister were admitted to the hospital due to recurrent thrush and thickening of their nails. Direct microscopic examination of their nails and the brother's tongue showed branched pseudohyphae and yeast cells, and Candida albicans was identified through fungal culture. The brother also experienced a progressively impaired vision, which was diagnosed as retinitis pigmentosa, causing no light perception in one eye and light perception up to 0.1 in the other. Their parents belonged to the Hui population (a minority population in China) and had a history of consanguineous marriage. Chronic mucocutaneous candidiasis (CMC) was diagnosed, and oral fluconazole was prescribed. After continuous fluconazole treatment for 6 months, the nails and the tongue became normal. These patients are still under follow-up.Due to the recurrent Candida infections and history of consanguineous marriage, genetic susceptibility was suspected. When we compared the WES data with all genes reported to be related to CMC, a homozygous mutation in the AIRE gene was noted (C. 769 C >T, p. Arg257Ter) in both patients. The parents were heterozygous carriers of the variant.ConclusionIn this study, we identified two CMC patients of Chinese harboring AIRE mutations. These patients remind us the importance of genetic analysis in management of CMC, which then help to adjust the time of treatment, as well as to predict and early detect related complications.

Corneal histomorphology and electron microscopic observation of R124L mutated corneal dystrophy in a relapsed pedigree.

To investigate the histological characteristics and ultrastructure of recurrent Chinese R124L mutated corneal dystrophy after keratoplasty. The subjects were enrolled from a Chinese family of corneal dystrophy with R124L heterozygous gene mutation and with a history of consanguineous marriage. Normal corneal samples were used as controls. In this family, 2 patients (3 eyes) underwent penetrating keratoplasty (PKP) and 2 patients (4 eyes) underwent lamellar keratoplasty (LKP). They had recurrence at 33.5±3.0 (range 30-36)mo after keratoplasty. Among them, 1 patient (1 eye) underwent PKP again and 1 patient (2 eyes) underwent LKP again. In the R124L mutated recurrent corneal dystrophy, the corneal turbidity was mainly distributed from the upper corneal cortex to the anterior stroma; the corneal epithelium surface was rougher and more uneven; and, the corneal erosions were larger. Hematoxylin-eosin staining showed that the thickness of the corneal epithelium was uneven; the arrangement of the epithelial cells was disordered; and, some corneal epithelial cells were swollen. The results of Congo red staining, Masson's trichrome staining and Periodic acid-Schiff staining were positive, while that of Alcian blue staining was negative. Under a transmission electron microscope, deposition of high electron density substances between epithelial and basal cells, and, apoptosis of basal cells were observed. Many high electron density depositions were observed in the sub-epithelial and anterior corneal matrix. In the Chinese family of recurrent corneal dystrophy with R124L gene mutation, the corneal epithelia of the recurrent cases are rougher, and the corneal depositions are extracellular amyloid fibrin.

Children with lysinuric protein intolerance: Experience from a lower middle income country.

BACKGROUNDLysinuric protein intolerance (LPI) is an inborn error of metabolism consequential to recessive mutations in the SLC7A7 gene. The metabolic imbalance in absorption and excretion of dibasic amino acids is considered the basis of LPI. The disease results from protein intolerance with signs and symptoms oscillating from cerebral impairment, respiratory involvement, renal failure and autoimmune complications.AIMTo determine biochemical and clinical presentation of cases with biochemical picture suggestive of LPI in Pakistani children.METHODSThe study was conducted at the Biochemical Genetic Lab, Department of Pathology and Laboratory Medicine, AKU Plasma, and urine amino acid quantification data from January 2013 to October 2018 was included in this study. The amino acids were analyzed by high performance liquid chromatography. Prestructured requisition forms were used to obtain the clinicopathological data. Statistical analysis was done by Microsoft Excel 2017.RESULTSA total of 6 patients were recognized. All the patients were male (100%). The mean age was 24 mo ± 10 d. All the patients had low plasma concentration of lysine, ornithine and arginine, whereas increased levels of lysine, ornithine and arginine in urine were observed in 2 patients. History of consanguineous marriage was present in all patients (100%). The most observed clinical symptom was feeding difficulty followed by failure to thrive (83.3%) and developmental delay (66.6%). Hepatomegaly was present in all patients (100%). No mutation analysis was done.CONCLUSIONThis study portrays the biochemical and clinical spectrum of LPI in Pakistan. Although clinical manifestations appeared in the first 2 years of life, most of them suffered a delay in undergoing diagnostic workup.

Hematopoietic Stem Cell Transplantation in Patients with Severe Combined Immunodeficiency: A Single-Center Experience

Objective: The aim of this study was to determine the factors affecting outcomes in patients who underwent hematopoietic stem cell transplantation (HSCT) with the diagnosis of severe combined immunodeficiency (SCID). Furthermore, our aim is to share our singlecenter experience of HSCT among SCID patients. Materials and Methods: The data of patients who underwent HSCT with the diagnosis of SCID between January 2014 and January 2021 in the pediatric bone marrow transplant unit of Istanbul Medipol University were retrospectively analyzed. Demographic and clinical data, treatment regimens, donor source, type of transplantation, pre- and post-transplantation infections, and complications were evaluated. Results: Among fifteen patients who underwent HSCT, 5 (33%) were female. The mean age at diagnosis was 3 months (1-6 months), and at transplantation 6 months (3-10 months). The mean time from diagnosis to transplantation was 3 months (2-9 months). There was a history of consanguineous marriage in thirteen (87%) and sibling death in eight (53%) cases. As donors, six (40%) were siblings and five (33%) were unrelated, while four (27%) patients underwent haploid transplantation. Four (27%) patients died during the first 100 days of transplantation. The median follow-up period was 23 months (9-61 months). Overall survival probability was calculated as 73%. Conclusion: SCID should be considered as an emergency in pediatrics. Devastating complications, including severe organ damage, lifethreatening infections, and even death, could appear in case of diagnostic delay. HSCT is a currently available curative treatment option. Subjects with a confirmed diagnosis should be referred to the appropriate bone marrow transplant center and treated as soon as possible.