In-depth exploration of differences of sex development: 5-year experience in a tertiary center.

BACKGROUND: Differences/disorders of sex development (DSD) encompass a wide range of conditions. Their clinical spectrum and etiological diagnosis have not been reported in Moroccan patients. AIMS: The study aims to highlight the clinical spectrum, etiological diagnosis, and management of patients with DSD. PATIENTS AND METHODS: This is a retrospective study of all patients diagnosed with DSD under the age of 18 years, who were referred to the Pediatric Endocrinology Department and the Medical Genetics Laboratory at HASSAN II University Hospital of Fez between June 2018 and June 2023. RESULTS: Out of 57 patients, 54.4% (n=31) were diagnosed with 46,XX DSD, the most common type, while 45.6% (n=26) had 46,XY DSD. Patients with 46,XX DSD presented earlier than those with 46,XY DSD, at a median age of 0.08 years and 0.96 years, respectively. The most commonly reported complaint was atypical genitalia. At the first presentation, the sex of rearing was already assigned to 26 males and 27 females. All patients with 46,XX DSD were diagnosed with congenital adrenal hyperplasia (CAH) at a median age of diagnosis of 0.92 years. Of these, 11 patients were raised as males. Disorders of androgen action or synthesis were more common in XY patients (69.2%). The consanguinity rate was 46.5%, and there were 19 cases with a positive family history, with 10 siblings having died. CONCLUSION: DSDs are not rare in Morocco. Overall, CAH remains the most frequent DSD etiology. Molecular genetic analyses are needed to determine accurate etiological distribution of DSDs, especially in XY patients.

Rapunzel syndrome complicated with pancreatitis, intussusception and intestinal perforation.

We report a case of a 4-year-old girl with limited financial resources, a background history marked by chronic abdominal discomfort and a positive Helicobacter pylori stool antigen test. The child presented with pallor, striking epigastric pain, nausea and vomiting. Blood tests reported high serum lipase levels. Investigations showed proof of nodular gastritis, intussusception and mild acute pancreatitis. The surgical procedure revealed Rapunzel syndrome complicated with intussusception and intestinal perforation, successfully treated. The postoperative course went uncomplicated.

Molecular and clinical assessment of maturity-onset diabetes of the young revealed low mutational rate in Moroccan families.

Background: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance. To offer an adequate patient management and therapeutic treatment for MODY patients, in addition to an early efficient diagnosis of their asymptomatic relatives, it is crucial to set an accurate molecular diagnosis. Hence, our aim was to determine the frequency of HNF1A and GCK genes among Moroccan-suspected MODY patients. Methods: Twenty suspected MODY patients were screened for HNF1A and GCK mutations using Sanger sequencing and MLPA methods. Segregation analysis of identified mutations was performed among family members. The pathogenic nature of missense variants was predicted using bioinformatic tools. Results: A total of two mutations were revealed among all patients raising the diagnostic rate to 10%. We identified a large novel GCK deletion (c.209-?_1398+?del) by MLPA in one patient and a previously reported missense substitution (c.92G > A) in HNF1A gene. Conclusion: This is the first investigation to perform the molecular diagnosis of MODY suspected patients. Our findings constitute a primary contribution towards unraveling the genetic landscape involved in the pathogenesis of MODY disease in Morocco.

[Biological variation of glycation and mean blood glucose have greater influence on Hba1c levels in type 1 young diabetic patients than glucose instability]. / La variation biologique de la glycation et la moyenne glycémique ont une plus grande influence sur l'HbA1c des jeunes diabétiques de type 1 que l'instabilité glycémique.

The aim of the study was to assess the relative influence of mean blood glucose (MBG), glucose instability (GI) and biological variation of glycohemoglobin (BVG) on HbA1c. The study included 378 unselected young type 1 diabetic patients with a diabetes duration > 1 year. There were 1,409 visits with simultaneous HbA1c determinations and self-monitoring of BG meter downloads. GI was quantified by measuring the standard deviation (SD) of the recorded BG values. A statistical model was developed to predict HbA1c from MBG. Hemoglobin glycation index (HGI) was calculated (HGI = observed HbA1c--predicted HbA1c) for each visit to assess BVG based on the directional deviation of observed HbA1c from that predicted by MBG in the model. Afterwards, the population was divided by thirds into high-, moderate-, and low-HGI groups, i.e. high-, moderate-, and low-glycators, reflecting BVG. A total of 246,000 preprandial BG measurements were analysed, with a mean of 177 per visit. Grand MBG +/- SD was 171 +/- 40 mg/dl. Predicted HbA1c was calculated from the equation: 3.8399 + 0.0242 x MBG (r = 0.66; p < 0.0001). A MBG change of 40 mg/dl corresponded to 1% change in HbA1c, within the range 6-12%. Multiple regression analysis showed no significant relationship between SD and HbA1c, after adjustment for MBG. MBG was 10 times more important than SD to predict HbA1c. MBG was not statistically different between the high- and low glycators, but HbA1c was significantly different. Multiple linear regression was used to predict HbA1c from MBG, SD and BVG (measured by HGI), adjusted for age, duration, gender and ethnic origin. BVG and MBG had large influences on HbA1c, the impact of BVG being 84% of the impact of MBG. On the other hand, GI had only 17% of the impact of MBG. In conclusion the effect of BVG on HbA1c is independent and much greater that the influence attributable to GI. Hemoglobin glycation phenotype, responsible for BVG, may be important for the clinical assessment of diabetic patients in order to avoid complications.

[Macrophage activation syndrome revealing subcutaneous T-cell lymphoma in a 16-year old adolescent]. / Syndrome d'activation macrophagique révélant un lymphome T sous-cutané chez un adolescent de 16 ans.

Macrophage activation syndrome (MAS) is a multisystemic disorder resulting from an over-activation of the immune system leading to a more or less diffuse macrophagic infiltration into the tussues. Clinical signs including fever, hepatosplenomegaly, adenopathy are associated with abnormal values in laboratory test results (bi or pancytopenia, hepatic cytolysis, elevated LDH levels, coagulopathy) and hemophagocytosis. In children, it can be primary or secondary to several disorders. We report the case of a 16-year old patient admitted to the Department of Pediatrics with febrile leukopenia associated with impaired general condition and circular erythematous lesions spread to the lower limbs. The diagnosis of macrophage activation syndrome was retained based on clinical signs, laboratory test results and cytological results. Skin biopsy of these lesions showed subcutaneous panniculitis-like T-cell lymphoma. The purpose of this study is to insists on the peculiarities of this clinical case given the rarity of this type of subcutaneous T-cell lymphoma, much more in this age group. We want to highlight the importance of suspecting subcutaneous T-cell lymphoma in patients with MAS associated with subcutaneous erythematous lesions because this could be life threatening.

Cutis Laxa syndrome: a case report.

Cutis laxa (CL) is a heterogeneous group of inherited and acquired connective tissue disorders characterized by a loose skin and variable systemic involvement (inguinal hernia, cardiopulmonary disease, and emphysema). Autosomal dominant, autosomal recessive and x-linked recessive patterns have been described in the inherited forms. Acquired forms of this disease have been associated with a previous inflammatory skin disorder (urticaria…). The characteristic symptomatological pattern is resulting from paucity of elastic fibers. We report an 18 months old baby boy with a congenital cutis laxa. He was admitted in pediatric unit for respiratory disorders. The diagnosis of CL syndrome is based on clinical assessment of typical skin features and the associated extracutaneous finding.

Hodgkin's Lymphoma Revealed by Hemophagocytic Lymphohistiocytosis in a Child.

Hemophagocytic lymphohistiocytosis (HLH) is a severe life-threatening disorder, responsible for extensive phagocytosis of hematopoietic cells and causing a multisystem organ failure. If lymphomas are common causes of HLH, the association with Hodgkin's lymphoma is rarely described in children. We report a case of a 9-year-old boy presenting with HLH as an initial manifestation of Hodgkin's lymphoma. He has been suffering from persistent high fever, asthenia, weight loss, and hepatosplenomegaly with no lymphadenopathy. The diagnosis of HLH secondary to infectious disease was initially worn. The patient received high-dose intravenous immunoglobulin with broad-spectrum antibiotics. However, his state got worse with the onset of dry cough and pleural effusion. Histopathologic examination of pleural fluid showed the presence of Reed-Sternberg cells. The outcome was favorable after treatment by corticosteroid and chemotherapy. Hodgkin's lymphoma revealed by HLH is a source of delayed diagnosis and should be borne in mind in children.

Severe hypernatremic dehydration associated with cerebral venous and aortic thrombosis in the neonatal period.

Severe neonatal hypernatremia is an important electrolyte disorder that has serious effects. Cerebral venous thrombosis and aortic thrombosis are relatively rare in severe neonatal hypernatremic dehydration. The authors report a case of cerebral venous thrombosis, associated with aortic thrombosis revealed by dehydration in a 9-day-old boy. Diagnostic was performed using Doppler ultrasound and imaging techniques. Thrombosis was resolved after anticoagulation treatment with low-molecular weight heparin for 1 month, and then was substituted by oral anticoagulant. The case report is followed by a review of the literature dealing with clinical, aetiological and therapeutic aspects of neonatal thrombosis.

Juniper tar (cade oil) poisoning in new born after a cutaneous application.

Juniper tar (cade oil) is distilled from the branches and wood of Juniperus oxycedrus. It contains etheric oils, triterpene and phenols, used for many purposes in folk medicine. The authors report a case of a previously healthy new born treated with a topical application of Juniperus oxycedrus for atopic dermatosis The poisoning caused convulsions, collapsus, acute pulmonary oedema, renal failure and hepatotoxicity. The newborn survived after supportive and symptomatic treatment, and discharged in a good condition on the eleventh day of hospitalisation in intensive care unit.

An unusual complication of subcutaneous fat necrosis of the newborn.

Subcutaneous fat necrosis (SCFN) is a well-described cause of subcutaneous calcification occurring in a young infant. Calcification of areas of fat necrosis in the neonate is a rare condition. In this case, the radiographic demonstration of soft-tissue calcification revealed the skin calcification in the absence of clinical signs of SCFN and without hypercalcaemia in the first 48 h of life.

Actuality of juvenile dermatomyositis.

Juvenile dermatomyositis is a rare disorder, but remains the most commonly occurring chronic inflammatory myopathy among children. Other than the proximal muscles and skin, which are routinely affected, vasculopathy may affect other viscera and can be multisystemic. A redefinition of the diagnostic criteria is currently underway and is likely to lead to other clinical signs and to sensitive and non-invasive examinations such as MRI. The impact of juvenile dermatomyositis on health and quality of life remains significant despite systemic corticosteroid therapy and immunosuppressor treatment, which have considerably improved the prognosis. Numerous predictors for favourable and pejorative evolution have been identified. The standardisation and the generalisation of clinical assessment tools will make it possible to carry out the clinical trials required to determine the relevance of the new therapeutic options available for children.

Intracerebellar haematoma simulating congenital medulloblastoma during neonatal period.

The authors report a case of intracerebellar haematoma occurring during the neonatal period. A 5-day-old baby girl was admitted because of poor feeding and the anterior fontanelle was tense. CT scan of the brain revealed a round mass at the cerebellar vermis; the lesion simulated a cerebellar tumour such as a medulloblastoma. The mass was surgically removed and found to be an intracerebellar haematoma. The clinical and radiologic characteristics are discussed.

[Lemierre syndrome]. / Syndrome de Lemierre.

Lemierre's syndrome is a rare and severe condition, with a primary focus in the cervicofacial area and followed by thrombosis of the internal jugular vein and metastatic infections, most often pulmonary. The principal pathogen is Fusobacterium necrophorum. Less rare and associated with high mortality before antibiotics, Lemierre syndrome had became exceptional until the increase in the number of cases in recent years. Recovery is usually the rule, but often only after long convalescence and often surgical intervention. The reemergence of this disease calls for a review of the literature to update knowledge about its epidemiologic, clinical, and therapeutic aspects.

Cerebral ischaemic stroke and bilateral pheochromocytoma.

We report a case of a 10-year-old girl who presented with an acute neurological deficit preceded by a 2 month history of headaches. The patient was treated for acute viral encephalitis because of the presence of inflammation. A computed tomography (CT) scan of her brain scan showed a cerebral ischaemic stroke, and paroxysmal arterial hypertension led us to suspect pheochromocytoma. The diagnosis was confirmed by elevated urinary catecholamine and by imaging (abdominal x-ray and abdominal/pelvic CT scan). Bilateral adrenal gland tumours were successfully removed. This report illustrates an uncommon presentation of pheochromocytoma in children and shows the importance of a careful investigation for pheochromocytoma as a cause of hypertension in children with cerebral ischaemic stroke.

Haemolytic disease of the newborn due to anti-c.

Anti-D isoimmunisation remains the most common cause of erythroblastosis fetalis. Whereas most clinically significant blood group sensitisations noted during pregnancy are still secondary to anti-D incompatibility, sensitisation to antigens other than D in the CDE system is not uncommon and can cause severe disease. The widespread use of Rh-D immune globulin has led to a relative increase in the importance of non-Rh-D isoimmunisation as a cause of haemolytic disease of the newborn. We report the case of a baby with severe hyperbilirubinaemia and persistent anaemia due to anti-c isoimmunisation with a high-titre maternal c antibody. The baby required emergency transfusion and intensive phototherapy. The medical literature relating to maternal c isoimmunisation and neonatal outcome is also reviewed. Because of its ability to cause clinically significant haemolytic disease of the newborn, practitioners must manage anti-c isoimmunisation in a manner similar to that for anti-D.

Lemierre syndrome: once seen it can never be mistaken.

Lemierre syndrome is a rare but severe septicaemia due most frequently to Fusobacterium necrophorum, with primary foci in the head, internal jugular vein thrombosis and metastatic infections, mainly in the lungs. We report two cases of Lemierre syndrome admitted to the paediatric unit of our hospital at 2-month intervals. The first was 10 years old and the second one was a 3-month-old infant. They were diagnosed on the 25th hospital day and at the time of admission, respectively. In the first case, diagnosis was delayed due to unfamiliarity with this disease. In the second patient the diagnosis was established on the first day because of the recent experience with patient 1. In both cases, bacteriological investigations were not helpful. Both patients had a favourable outcome after prolonged antibiotic treatment, anticoagulation and surgical drainage.