Genetic Diagnosis of Inborn Errors of Immunity in an Emerging Country: a Retrospective Study of 216 Moroccan Patients.

PURPOSE: Genetic testing provides great support to validate the clinical diagnosis of inborn errors of immunity (IEI). However, the high cost and advanced technology make these tests inaccessible to a large proportion of patients in low-income countries. In the present study, we aim to evaluate the Moroccan experience in genetic testing and to report the main molecular features and difficulties encountered in genetic diagnosis. METHODS: We performed a multi-center retrospective analysis of all patients with a molecular diagnosis and registered in the national registry between 2010 and 2022. To estimate the impact of the newly identified mutations, we calculated the Combined Annotation Dependent Depletion (CADD) score and the mutation significance cutoff (MSC) for each variant. RESULTS: A total of 216 (29%) patients received a genetic diagnosis out of 742 patients with IEI included in the registry. All genetic tests were performed in the context of thesis projects (40%) or international collaborations (60%). A set of 55 genetic defects were identified, including 7 newly reported: SNORA31, TBX21, SPPL2A, TYK2, RLTPR, ZNF341, and STAT2 GOF. Genetic diagnoses were more frequent in the defects of innate and intrinsic immunity with a percentage of 78%, while antibody deficiencies had a lower frequency with a percentage of 17.5%. Only one genetic diagnosis has been made in the complement deficiency group. The most commonly used molecular techniques were Sanger sequencing (37%) followed by targeted gene sequencing (31%). CONCLUSION: The thesis projects and collaborations were beneficial as they allowed us to provide a definitive genetic diagnosis to 29% of the patients and to contribute to the identification of new genetic defects and mutations. These results offer insight into the progress made in genetic diagnoses of IEI in Morocco, which would provide a baseline for improving the clinical management of patients with IEI.

A Serendipitous Finding of Coagulation Factor VII Deficiency in Two Asymptomatic Patients.

Congenital Factor VII (FVII) deficiency is a rare autosomal recessive disorder with a prevalence of approximately 1:500,000. It plays a crucial role in initiating coagulation by activating Factors IX and X. Diagnosis typically involves prolonged prothrombin time (PT) and varies widely in clinical presentation. Management includes fresh frozen plasma (FFP), prothrombin complex concentrates (PCC), and recombinant activated FVII (rFVIIa), with rFVIIa often preferred due to its safety and efficacy. We present two pediatric cases: a five-year-old boy with a prolonged PT at 55% and FVII levels at 25.1%, and a two-year-old boy with a PT at 24% and FVII levels at 4.6%. Both cases highlight the importance of thorough hemostatic evaluation and tailored management strategies in FVII deficiency.

Portal Hypertension in Children: Investigating Umbilical Catheterization in the Neonatal Period.

Portal cavernoma is a major cause of extrahepatic portal hypertension (EHPH) in children. It is a serious condition, due to the frequency and severity of digestive hemorrhages secondary to the rupture of esophageal varices (EV). Neonatal umbilical catheterization is a significant risk factor for the development of portal vein thrombosis (PVT) and portal hypertension. We report a case of a five-year-old male who presented with upper gastrointestinal (GI) bleeding on ruptured esophageal varices resulting from a portal cavernoma, complicating neonatal umbilical vein catheterization. This case illustrates the risk of severe vascular complications, particularly portal hypertension that can result from neonatal umbilical vein catheterization.

Sanjad-Sakati Syndrome Revealed by Hypocalcemic Convulsions.

Sanjad-Sakati syndrome is an autosomal recessive disorder characterized by facial dysmorphia, growth retardation, and congenital hypoparathyroidism. Epidemiologically, this syndrome is primarily observed in children of Arabian descent. However, cases have also been reported in non-Arab countries. Although its exact prevalence is uncertain, the estimated incidence in Saudi Arabia ranges from one in 40,000 to one in 600,000 live births. We report a case of Sanjad-Sakati syndrome in a female infant, born to first-degree consanguineous parents, who presented with convulsive seizures since the age of four months. Laboratory findings indicated severe hypocalcemia and elevated phosphate levels, consistent with congenital hypoparathyroidism. The treatment involved calcium and vitamin D supplementation, which led to a marked improvement in the patient's condition. The objective of this clinical case is to highlight an uncommon cause of hypocalcemia and to describe certain clinical and endocrinological manifestations of Sanjad-Sakati syndrome, which is prevalent in the Arab population.

Exploring the Link Between Profuse Warts and Hyper-Immunoglobulin E (IgE) Syndrome: A Pediatric Case Report.

The relationship between warts and hyper-immunoglobulin E (IgE) syndrome lies in the fact that patients with this syndrome may have recurrent or persistent skin warts because of their immune dysfunction. Therefore, it is important to consider this possibility when evaluating a patient with skin warts, especially if they are associated with other symptoms such as recurrent infections or pulmonary issues. Warts can thus be an important clinical sign indicating the presence of this syndrome. We report the case of a young girl presenting with numerous warts accompanied by pulmonary involvement and weight delay, in whom the diagnosis of hyper IgE syndrome was established.

Hematemesis in Children: A Potential Sign of Parental Psychiatric Disorder.

Munchausen's syndrome by proxy (MSBP) is a rare form of abuse characterized by the fabrication or induction of symptoms of illness in a child by a close relative, typically a parent, leading to multiple consultations and varying degrees of invasive medical interventions. Various clinical presentations are described in the literature, ranging from organic manifestations to psychiatric expressions. This syndrome remains a challenging diagnosis to make and requires increased awareness among healthcare professionals. Prompt recognition is key to preventing potential long-term comorbidities and even fatalities. Here, we are reporting two cases of MSBP manifested by bleeding, with the perpetrator being the mother.

Primary Immunodeficiency-Type Ataxia-Telangiectasia Revealed by Splenic Abscesses.

Ataxia-telangiectasia (A-T) is a rare inherited autosomal recessive disease. It is associated with an alteration in the ATM gene, located on chromosome 11q22-23, which codes for a protein involved in a complex way in cell cycle regulation and cell protection. It is characterized by cerebellar ataxia, cutaneous and ocular telangiectasia, and an immune deficiency responsible for recurrent infections. Diagnosis is generally delayed due to the late onset of neurological symptoms and telangiectasia. People suffering from this condition are particularly sensitive to ionizing radiation, which considerably increases their risk of developing neoplasia. We report an observation of a primary immunodeficiency-type A-T revealed by recurrent fever and multiple splenic abscesses.

Vitamin B12 Deficiency in Infants With Axial Hypotonia and Psychomotor Regression: Insights From a Moroccan Case Study.

Vitamin B12 deficiency is a rare entity in the pediatric population. It is often of maternal origin in exclusively breast-fed infants. Its clinical manifestations are multiple and unspecific, encompassing hematological problems and neurodevelopmental consequences. Positive diagnosis and early treatment with vitamin B12 supplementation have a rapidly reversible effect on symptoms. Delayed diagnosis, however, may result in irreversible neurological sequelae. We report the case of a six-month-old infant, admitted with hypotonia and psychomotor regression since the age of four months. The laboratory work-up revealed macrocytic anemia with the presence of megakaryocytes and megaloblasts on the myelogram. Vitamin B12 levels were low, and homocysteine levels were high. A maternal workup showed vitamin B12 deficiency in the mother. A brain MRI showed bilateral frontoparietal cortical atrophy. The patient was put on vitamin B12 supplementation with good evolution. The aim of our work is to shed light on the misleading and varied clinical profile of vitamin B12 deficiency in an exclusively breastfed infant, the serious consequences of maternal vitamin B12 deficiency, and the importance of early diagnosis of this condition.

Acute Myocardial Infarction in a Seven-Year-Old Child With Type 1 Diabetes: A Rare Case Report.

Myocardial infarction (MI) is extremely rare in children and can have different etiologies, including congenital heart defects and Kawasaki disease. Cardiovascular disease (CVD) is the primary cause of death in patients with type 1 diabetes (T1D). Effective management of risk factors like blood pressure, cholesterol, and blood sugar levels is essential for individuals with T1D to mitigate the risk of cardiovascular complications, including MI. We present the case of a seven-year-old child diagnosed with type 1 diabetes one month before this admission, without any other notable medical history, who was admitted to the pediatric emergency department due to chest pain. The symptoms had begun two hours prior to admission. Upon arrival, the patient reported severe and persistent retrosternal constrictive chest pain radiating to the left arm without other associated signs, with a strictly normal clinical examination. An electrocardiogram (ECG) revealed typical ST segment elevation in inferior leads (II, III, and aVF) with reciprocal changes in V1 to V4. Troponin level was elevated at 7254 ng/l. Echocardiography revealed mild dilation of the left coronary artery (4 mm) and the right coronary artery (3 mm), while other radiological and laboratory investigations showed no abnormalities. The patient responded well to treatment with acetylsalicylic acid, clopidogrel, and heparin, resulting in a favorable outcome.

Prevalence and Determinants of the Use of Antibiotics by Self-Medication in the Pediatric Population in Oujda, Morocco.

OBJECTIVE: Antibiotic resistance driven by antibiotic self-medication and inappropriate use of antibiotics is a growing global health threat. Our study aimed to describe parents' self-medication practices with antibiotics, determine the factors favoring their use in the pediatric population, and assess parents' knowledge of the role of antibiotics and antimicrobial resistance. MATERIALS AND METHODS: We conducted a cross-sectional study over two months (September and October 2023). Data collection was performed using a questionnaire-guided interview. We included 460 parents of children consulting or hospitalized in the Pediatric Department of the University Hospital Mohammed VI in Oujda, Morocco. RESULTS: A total of 62% of parents questioned were mothers. Self-medication with antibiotics was noted in 313 families (68%). Parents used antibiotics mainly to treat cough (43%) and fever (24%). Betalactams were the antibiotic class most used by parents (72%). Information on dosage and methods of antibiotic administration was provided by pharmacy staff but was not respected by most parents (78%). Efficacy of treatment (58%), saving consultation costs and time (47%), and the ease of obtaining treatment without a prescription (42%) were reported in the majority of cases as reasons for using antibiotics by self-medication. In our context, the probability of self-medicating with antibiotics in the pediatric population is increased by female gender (OR=1.04), low level of education (OR=1.02), low socio-economic status (OR=1.09), and buying antibiotics without a prescription (OR=1.22). CONCLUSION:  Although antibiotic self-medication in children is a worldwide phenomenon, influenced by several geographical, cultural, and economic factors, there is an urgent need to promote a global health strategy.

Christ-Siemens-Touraine Syndrome: A Report of a Rare Pediatric Case.

Anhidrotic ectodermal dysplasia (AED), or Christ-Siemens-Touraine syndrome, is an X-linked recessive dermatosis. Rare in incidence, it affects 1 in 100,000 births, mostly boys. Through this observation, we detail the clinical signs that led us to suspect the diagnosis, how this pathology was confirmed, and the therapeutic management we carried out. We present a case of a 10-month-old boy presenting with altered manifestations affecting almost all the ectodermal structures like skin, hair, nails, teeth, sebaceous glands, sweat glands, and tear glands. He also had complete anodontia and a dry mouth. A multidisciplinary treatment was given to the patient with the collaboration of various health professionals. Although Christ-Siemens-Touraine syndrome is a rare condition, it is vital to recognize it early to improve care and prognosis for these patients, while mitigating the psychological impact of the condition on both children and parents.

Celiac Disease and Autoimmune Diseases in a Pediatric Population in Morocco: A Cross-Sectional Study.

INTRODUCTION: Celiac disease (CD) is defined as an autoimmune disease (AD) caused by gluten ingestion in genetically sensitive individuals. Several publications have demonstrated the increased risk of AD in patients with CD, both adults and children, which requires systematic research. Our study aimed to determine the prevalence of AD in 60 patients diagnosed with CD and to highlight risk factors that may contribute to the emergence of AD. MATERIALS AND METHODS: We collected medical data from all CD patients under 16 years of age who also had AD. Our study was conducted in the Gastroenterology-Hepatology and Pediatric Nutrition Unit of the Pediatrics Department of the Mohamed VI Hospital and University Center in Oujda, Morocco, during a seven-year period between January 2017 and January 2024. RESULTS: We studied 60 patients with CD in our study. Eight patients (13%) had an associated AD. Their average age was eight years, with extremes varying between two and 15 years. AD was diagnosed before CD in six cases (75%), in parallel with CD in one patient (12.5%), while in only one case, it was diagnosed after CD (12.5%). All our patients had a single AD associated with CD. These ADs were mainly type 1 diabetes in seven cases and autoimmune thyroiditis in only one case. All our patients followed a gluten-free diet in addition to specific treatment for associated AD. Nevertheless, despite regular medical follow-up and targeted dietary advice for the management of CD and associated AD, three patients encountered difficulties in following the recommended diet. CONCLUSION: Younger patients with CD have an increased risk of hypothyroidism and insulin-dependent diabetes. These data necessitate improved surveillance to discover these illnesses as early as possible in order to optimize management and reduce related consequences.

Ophthalmic Shingles in Children: A Rare Form and a Danger to Be Aware of.

Shingles in children is rare, especially the ophthalmic form. The occurrence of shingles in children is exceptional but often benign, requiring only symptomatic treatment. Antivirals are exceptionally used for complicated forms, which are mainly seen in immunocompromised individuals or in ophthalmic locations that can lead to severe ocular complications. Various studies agree on the benign nature of this condition in immunocompetent children and an excellent prognosis. We report a case of ophthalmic shingles in an immunocompetent child aged two years and seven months. The purpose of this clinical case was to emphasize the importance of early antiviral treatment to limit corneal involvement and preserve visual function.

Acceptance, Hesitancy, and Refusal Among Parents of Young Girls in Relation to Human Papillomavirus Vaccination: A Study From the Mohammed VI University Hospital Center in Oujda, Morocco.

INTRODUCTION: Morocco has joined the global efforts to eliminate cervical cancer by introducing human papillomavirus (HPV) vaccination into its national immunization program. However, vaccination rates remain insufficient relative to the importance of the vaccine. Therefore, the objective of the study was to understand better the factors associated with acceptance, hesitance, or refusal of the HPV vaccine. MATERIALS AND METHODS: A descriptive and analytical study was conducted among 450 parents of girls of HPV vaccination age at the Mohammed VI University Hospital Center in Oujda, Morocco, over a period of three months. RESULTS: A total of 450 parents were included in the study, most of them being mothers. Most parents were unaware of HPV infection (66%) or the HPV vaccine (62%). The rate of HPV vaccination among the study population was only 33%. Factors associated with nonvaccination included a lack of information about the HPV vaccine (57%), concern about side effects (33%), and unvaccinated family and friends (10%). Parents' intention to vaccinate their daughters was significantly lower in fathers (95% confidence interval, or 95% CI = 0.34-0.66), those with a low educational level (odds ratio, or OR = 0.53; 95% CI = 0.40-0.80), and those with an unfavorable socioeconomic level (OR = 0.41; 95% CI = 0.30-0.56), whereas it was significantly higher in cases of a vaccinated entourage, including friends and family (OR = 1.52; 95% CI = 1.22-2.12), and when vaccination was recommended by a doctor (OR = 1.92; 95% CI = 1.56-2.39). CONCLUSION: The results of our study highlighted parents' lack of information about HPV infection and the HPV vaccine. They also revealed a clear lack of HPV vaccination coverage and identified the reasons for reluctance to vaccinate against HPV. Much remains to be done to increase the rate of HPV vaccination in Morocco.

A Rare Case Report of Benign Intracranial Hypertension Caused by Hypervitaminosis A.

Benign intracranial hypertension (BIH) in children is recognized as elevated intracranial pressure without hydrocephalus or intracranial mass. It manifests differently in adults, with no apparent predilection for sex or weight. Headache, papilledema, and possibly sixth nerve palsy with visual field defects are the typical symptoms of this syndrome. Vitamin A toxicity is a rare cause of BIH. We report the case of a previously healthy 13-year-old girl presenting with photophobia, a frontal headache, and vomiting. She had bilateral papilledema discovered by fundoscopy. Both magnetic resonance imaging and brain CT were normal. At admission, a lumbar puncture (LP) revealed an opening pressure of 26 cm H2O with normal cerebrospinal fluid (CSF) analysis. The diagnosis of BIH was established, and treatment with acetazolamide was started, with good clinical results. Regular eye evaluations showed a regression of papilledema. Elevated serum vitamin A levels were the only positive findings. Within two weeks, the patient was discharged without any symptoms. This study aims to attract the attention of clinicians to the importance of evaluating vitamin A toxicity in the context of papilledema and oculomotor problems in a child who has undergone normal neuroradiological investigations.

A Case Report of an Uncommon Association of Total Intracardiac Anomalous Pulmonary Venous Return and Tetralogy of Fallot.

Total anomalous pulmonary venous return (TAPVR) represents a group of anomalies consisting of a lack of connection between the pulmonary veins and the left atrium. All oxygenated pulmonary venous return flows directly or indirectly into the right atrium. Survival is only possible with a right-to-left atrial shunt. It remains rare, accounting for less than 1% of all congenital heart diseases. Its association with tetralogy of Fallot is much rarer and has been documented in medical literature as isolated cases. Early prenatal diagnosis, rapid surgical repair, and optimal postoperative resuscitation appear to be the best guarantee of a favorable outcome following total repair of a pulmonary venous connection anomaly. Non-obstructed forms present as high-flow shunts with moderate cyanosis. The symptomatology of blocked forms is dominated by the obstruction to venous return; a clinical picture of respiratory distress with intense cyanosis and severe pulmonary arterial hypertension develops from the first days of life. Echocardiography is fundamental in diagnosing TAPVR. If the results are inconclusive, magnetic resonance imaging and computed tomography are appropriate alternatives for establishing a complete and accurate diagnosis. We report a case of a two-month and 22-day-old infant who is a product of a twin pregnancy, presenting with a non-obstructed TAPVR associated with tetralogy of Fallot, and his twin who died on day 20 of life, likely due to a complex cyanotic congenital heart disease.

A Fatal Case Report of Chenopodium ambrosioides L. (M'khinza) Intoxication.

Chenopodium ambrosioides L. is a plant belonging to the Chenopodiaceae family, known for its use in traditional medicine as a remedy for its antiseptic, analgesic, antipyretic, antispasmodic, and anti-inflammatory properties. It is used for its therapeutic properties internally as an infusion or externally as a vermifuge. Its use can be responsible for serious, even fatal, side effects and intoxications, particularly in infants and children. These may include neurological, digestive, hepatic, or renal complications. We present a case of Chenopodium ambrosioides L. intoxication in a four-year-old girl, resulting from repeated high-dose infusions of this plant for antipyretic purposes. She was admitted to the pediatric emergency department for management of a disorder of consciousness four hours after ingesting Chenopodium ambrosioides L. to treat acute fever.

Beyond the Rib Cage: Unraveling Abernethy Syndrome as a Rare Cause of Cyanosis.

Abernethy syndrome is a rare congenital malformation stemming from a portosystemic shunt. Diagnosis proves challenging due to nonspecific clinical symptoms, with presentation varying based on age and disease severity. Consequences include hepatic, cardiovascular, renal, gastrointestinal, and neurological complications, and growth retardation. We report the case of a child presenting with perioral and digital cyanosis, observed in early childhood. Clinical examination revealed low saturation, telangiectasias, digital clubbing, and collateral venous circulation in the thorax. Imaging confirmed the diagnosis of Abernethy syndrome.

When Salmonella Manifests Through the Skin: Erythema Nodosum in a Pediatric Case.

Erythema nodosum (EN) is a non-specific nodular dermo-hypodermic rash characterized by the sudden occurrence of painful lumps located especially in the legs following a non-specific reaction to different internal and external antigens. Clinical and histological manifestations are stereotyped, regardless of the etiology. Erythema nodosum is most frequently associated with infections, particularly bacterial and less commonly viral, fungal, and parasitic. Other conditions can be discussed, including systemic diseases, malignant tumors, medicines, and vaccines. In almost half of cases, erythema nodosum is idiopathic if no cause is found. We report a case of erythema nodosum secondary to a Salmonella infection in a seven-year-old male. The peculiarity of our observation is the initial presentation of systemic signs that preceded the gastrointestinal symptoms.

Lupus Hepatitis: A Rare Manifestation Revealing Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a rare disease in children but is more severe than in adults. SLE may be associated with various non-specific hepatic manifestations, but subacute lupus hepatitis remains unusual and is rarely a mode of revelation. Diagnosis is based on a combination of clinical, laboratory, and histological findings after ruling out other causes of hepatitis, notably autoimmune hepatitis (AIH). We report the case of a young girl with undiagnosed SLE, which first revealed itself as liver involvement and progressed well on corticosteroid therapy. During the course of her illness, she presented with other manifestations that led us to think of SLE with lupus hepatitis.