Spectrum of Genital and Extragenital Anomalies in Malformation Syndromes Associated With 46, XY Disorders of Sex Development: A Single Center Experience.

OBJECTIVE: This study aimed at integrating the clinical and phenotypic characteristics, hormonal profile and genetic diagnosis of children with malformation syndromes associated with XY disorders of sex development (DSD) in a single-center in Egypt. METHODS: This retrospective study included patients with syndromic XY DSD recruited from the Pediatric Endocrinology and Surgery units at Alexandria University Children's hospital (AUCH), Alexandria, Egypt, during the period between 2018 and 2023. All patients included in the study underwent a detailed clinical and laboratory evaluation, ultrasonography (and laparoscopy if needed); and decision making was done accordingly. RESULTS: The study included 30 children with syndromic XY DSD; most of these children were diagnosed at birth. The most common extragenital malformations included skeletal anomalies (70%), facial dysmorphism (46.7%), cerebral malformations and congenital heart disease (23.3%). Ventricular septal defect was the most common congenital heart disease. CONCLUSION: Integration between clinical, laboratory and genetic data is the cornerstone in the management of XY DSD patients for appropriate decision making of surgical intervention and sex assignment, in addition to screening for other associated features of each mutation.

Spectrum of Genital and Extragenital Anomalies in Malformation Syndromes Associated With 46, XY Disorders of Sex Development: A Single Center Experience.

OBJECTIVE: This study aimed at integrating the clinical and phenotypic characteristics, hormonal profile and genetic diagnosis of children with malformation syndromes associated with XY disorders of sex development (DSD) in a single-center in Egypt. METHODS: This retrospective study included patients with syndromic XY DSD recruited from the Pediatric Endocrinology and Surgery units at Alexandria University Children's hospital (AUCH), Alexandria, Egypt, during the period between 2018 and 2023. All patients included in the study underwent a detailed clinical and laboratory evaluation, ultrasonography (and laparoscopy if needed); and decision making was done accordingly. RESULTS: The study included 30 children with syndromic XY DSD; most of these children were diagnosed at birth. The most common extragenital malformations included skeletal anomalies (70%), facial dysmorphism (46.7%), cerebral malformations and congenital heart disease (23.3%). Ventricular septal defect was the most common congenital heart disease. CONCLUSIONS: Integration between clinical, laboratory and genetic data is the cornerstone in the management of XY DSD patients for appropriate decision making of surgical intervention and sex assignment, in addition to screening for other associated features of each mutation.

Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa.

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment. METHODS: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records. RESULTS: Data from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth-37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age. CONCLUSIONS: This analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.

Clinical and molecular characteristics of infantile-onset diabetes mellitus in Egypt.

PURPOSE: In patients diagnosed with diabetes mellitus (DM) before the age of 12 months, there is an increasing recognition of diabetes caused by single-gene mutations, also known as monogenic diabetes of infancy or neonatal DM (NDM). This study aimed to classify patients at Alexandria University Children's Hospital (AUCH) diagnosed with infantile-onset DM into type 1 DM (T1DM) or NDM and to detect differences in molecular characteristics of NDM patients at our center in comparison to other countries. METHODS: This retrospective/prospective observational study was conducted on 39 patients diagnosed with infantile-onset DM (age of onset ≤1 year) at AUCH from January 2003 to November 2020. The patients were divided into 2 groups according to age at the onset of DM: ≤6 months and >6-12 months. Molecular testing was done in patients diagnosed with DM at ≤6 months and those with negative autoantibodies. RESULTS: Twelve patients were diagnosed with DM at age ≤6 months and 27 patients were diagnosed between 6-12 months. Seventeen patients (43.6%) had T1DM, whereas 9 patients (23.1%) had genetically confirmed NDM, including 3 harboring novel mutations. The most common genetic causes of NDM were EIF2AK3 mutations (n=3), followed by KCNJ11 (n=2) and ABCC8 (n=2). Other mutations included SLC19A2 (n=1) and INS (n=1). Three patients with potassium ATP channel mutations were transferred from insulin to sulfonylurea treatment. CONCLUSION: It is essential to identify patients with NDM clinically and confirm the diagnosis by molecular testing to distinguish them from T1DM as it helps in refining their management, predicting prognosis, and guiding genetic counseling.

Intussusception in preterm neonates: A systematic review of a rare condition.

BACKGROUND: While necrotizing enterocolitis (NEC) is a prevalent condition in preterm neonates admitted to neonatal intensive care unit (NICU), intussusception is exceedingly uncommon and often overlooked. This is due to the fact that they share many clinical characteristics. The initial misdiagnosis of intussusception in preterm neonates (IPN) especially has led to a delay in their management, which increases the risk of developing compromised bowel. Additionally, it is difficult to reach a diagnosis as neonatal intussusception does not have any classical radiological signs even when contrast enema is used. This systematic review is based on the published literature including case reports and case series to review the clinical features of IPN and how to differentiate it from NEC in order to shed the light on this rare disease and how having a high index of suspicion would help practitioners to make an early and accurate diagnosis METHODS: A systematic literature search to report all cases of relevant articles that reported IPN till date. All cases that were born before 37 weeks gestational age, presented within the neonatal period and having well established documentation were included in the study. Any case that did not have these criteria was excluded from our study. RESULTS: Only 52 cases met these criteria during the period from 1963 till date. An average of 10 days had elapsed before the cases were confirmed to have IPN either clinically or intraoperatively. The most frequent manifestations were abdominal distension and bilious gastric residuals, occurring in 85% and 77% of the cases respectively, followed by bloody stools in 43% of cases. However, this triad was present only in approximately one-third of the cases. Only 13 cases were diagnosed as having intussusception preoperatively. About two thirds of the intussusception were located in the ileum. Pathological lead point was present in 7 cases only; 4 of them were due to Meckel's diverticulum. Nine cases only out of the 52 cases with IPN died. CONCLUSION: It is crucial to detect the clues for diagnosis of intussusception because in contrast to NEC, it is unresponsive to conservative management, affects the viability of the bowel and surgery is essential.

Huge ovarian cyst in a neonate with classical 21-hydroxylase deficiency.

Congenital adrenal hyperplasia is the most common cause of ambiguous genitalia worldwide, with an incidence of 1 in 15,000 live births. The most frequently-occurring subtype, 21-hydroxylase deficiency, results in diminished production of aldosterone and cortisol as well as increased androgen secretion. Previous studies have reported a relationship between ovarian cyst formation and adrenal androgen excess; nevertheless, neonatal large ovarian cysts have rarely been reported in newborns with congenital adrenal hyperplasia. Herein, we present the unique case of a neonate with classical 21-hydroxylase deficiency who underwent surgery for a huge unilateral solitary ovarian follicular cyst on the seventh postnatal day. Possible mechanisms by which androgen excess may cause ovarian cyst formation are also discussed.

Gastroduodenal Intussusception Due to Gastric Mucosal Prolapse Polyp in a 2-Year-Old Child.

BACKGROUND: Gastroduodenal intussusception is an invagination of a portion of the stomach into the duodenum. It predominately occurs in adults. Case Report: We present a gastroduodenal intussusception in an hypochromic microcytic anemic 2-year-old girl. A large filling defect in the second and third parts of the duodenum, indenting the pyloric antrum, was due to a gastroduodenal intussusception secondary to a cauliflower-like gastric mucosal prolapse polyp, a type of gastric hyperplastic polyp. Conclusion: Anemia may accompany a gastric mucosal prolapse polyp.

Hemiscrotal agenesis: a novel phenotype of a rare malformation.

BACKGROUND: Hemiscrotal agenesis (HSA) is an exceedingly rare congenital anomaly in scrotal development. It is characterized by unilateral absence of scrotal skin with intact midline raphe. In the English literature, only seven patients were diagnosed with HSA. Herein, we report a 14-month-old boy with HSA, unilateral cryptorchidism and a perineal skin tag. Additionally, the patient had a monodactylous limb, unilateral cerebellar hypoplasia, and a cardiac septal defect. CASE PRESENTATION: A 14-month-old boy presented with right HSA and ectopic scrotal skin in the right perineal region. Extra-genital examination showed right monodactylous lower limb, without dysmorphic facial features or any other skeletal anomalies. His karyotype was 46, XY, while his hormonal profile showed prepubertal LH and FSH. Skeletal survey showed right monodactylous lower limb (with only a big toe which had 2 phalanges) and normal spine alignment. A previous echocardiography was done and showed a small muscular ventricular septal defect (VSD) that closed on follow-up. Magnetic resonance imaging of the brain showed posterior fossa malformation. The patient had his right testis fixed in the right scrotum. The pathological examination of the perineal lesion showed fibro-epithelial polyp (skin tag), with no testicular tissue or atypia. CONCLUSION: We believe that this is the first case to be reported with hemiscrotal agenesis and ipsilateral cryptorchidism, associated with a perineal skin tag, unilateral monodactylous lower limb on the same side, unilateral cerebellar hypoplasia, and VSD. Interestingly, further genetic analysis is required to reach a final diagnosis. However, regrettably, advanced molecular diagnostic studies for this patient is not available in our country.

Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients.

LPS-responsive beige-like anchor (LRBA) deficiency is an autosomal recessive primary immunodeficiency disorder, OMIM (#614700). LRBA deficiency patients suffer from variable manifestations including recurrent infections, immune dysregulation, autoimmunity, cytopenias, and enteropathy. This study describes different clinical phenotypes and immunological characteristics of 18 LRBA deficiency patients diagnosed from Egypt. T and B lymphocyte subpopulations, LRBA, and cytotoxic T lymphocyte-associated protein 4 (CTLA4) expression were evaluated in resting and stimulated T cells using flow cytometry. Next-generation sequencing was used to identify mutations in the LRBA gene. LRBA deficiency patients had significantly lower B cells and increased percentage of memory T cells. CTLA4 levels were lower in LRBA-deficient T regulatory cells in comparison to healthy donors at resting conditions and significantly increased upon stimulation of T cells. We identified 11 novel mutations in LRBA gene ranging from large deletions to point mutations. Finally, we were able to differentiate LRBA-deficient patients from healthy control and common variable immunodeficiency patients using a simple flow cytometry test performed on whole blood and without need to prior stimulation. LRBA deficiency has heterogeneous phenotypes with poor phenotype-genotype correlation since the same mutation may manifest differently even within the same family. Low LRBA expression, low numbers of B cells, increased numbers of memory T cells, and defective CTLA4 expression (which increase to normal level upon T cell stimulation) are useful laboratory tests to establish the diagnosis of LRBA deficiency. Screening of the siblings of affected patients is very important as patients may be asymptomatic at the beginning of the disease course.

Gallbladder Papilloma in a Child Unmasking Metachromatic Leukodystrophy: A Case Report With Review of Literature.

Background: Metachromatic leukodystrophy (MLD) is a lipid storage disease characterized the accumulation of sulfatides in different viscera including the gallbladder. Case report: A 2-year-old girl had upper right quadrant lesion that was preoperatively thought to be a biliary cystadenoma. Histologically, the gallbladder lesion was a tubulo-villous papilloma with multiple foci of papillary mucosal hyperplasia. Many storage histiocytes containing metachromatic granules, characteristic of MLD, were present in the tips of the papillae. MLD was later confirmed by enzyme studies. Conclusion: Gallbladder papilloma can be the presenting feature of MLD.