Clinical and molecular report of c.1331 + 1G > A mutation of the AAAS gene in a Moroccan family with Allgrove syndrome: a case report.

BACKGROUND: Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of achalasia, alacrimia and adrenal insufficiency. It is caused by the mutations of the AAAS gene located on chromosome 12q13. The c.1331 + 1G > A mutation is one of the most common described in North Africa including Tunisia, Algeria and Libya. We report here the clinical and genetic profile of a Moroccan family with Allgrove syndrome. CASE PRESENTATION: A Moroccan sister and brother born to consanguineous parents were found, at the ages of twelve and fifteen months old respectively, to have alacrimia and isolated glucocorticoid deficiency. Later, they developed achalasia whereupon Allgrove syndrome was diagnosed clinically and confirmed by DNA sequencing which revealed a c.1331 + 1G > A mutation in the AAAS gene. CONCLUSION: This finding reinforces previous studies in demonstrating the geographic expansion of the ancestral mutation c.1331 + 1G > A in North African patients and thus enabling targeted genetic counseling. To the best of our knowledge, this is the first report of the AAAS gene mutation in Moroccan patients.

[Vascular calcification in pseudoxanthoma elasticum in children]. / Calcifications vasculaires dans le pseudoxanthome élastique chez l'enfant.

INTRODUCTION: Vascular calcifications are associated with several diseases that affect vascular connective tissue and skin and cause considerable morbidity and mortality. The prototype of these conditions is pseudoxanthoma elasticum. We report, in this study, 4 pediatric cases of vascular calcifications diagnosed as elastic pseudoxanthoma. OBSERVATIONS: These 4 children were 2-11 years old and presented variable clinical features. Vascular involvement and arterial hypertension was observed in all patients, skin involvement in 2 cases, gastrointestinal involvement in 2 cases, neurological impairment in one case, and cardiac involvement in one case. Demonstration of ABCC6 gene mutations provided diagnostic confirmation in all cases. CONCLUSION: Pseudoxanthoma elasticum is a rare genetic disease, which can lead to many complications. Appropriate knowledge and early diagnosis are essential.

[Pseudoxanthoma elasticum: A rare cause of gastrointestinal bleeding in children]. / Pseudo-xanthome élastique : une cause rare d'hémorragies digestives chez l'enfant.

INTRODUCTION: Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive connective tissue disorder, characterized by calcification and progressive fragmentation of elastic fibers. Gastrointestinal lesions are rare in children and may be responsible for serious complications. This article reports two pediatric cases of PXE revealed by gastrointestinal bleeding. CASE REPORTS: An 11-year-old boy and a 12-year-old girl were hospitalized for gastrointestinal bleeding. Digestive endoscopy showed hemorrhagic gastroenteritis bulbitis in the first case and it was normal in the second. Abdominal ultrasound showed diffuse linear calcifications in both cases. The diagnosis of PXE was retained based on the presence of vascular disease in both patients, a skin lesion in the girl, and an ocular lesion in the boy. The genetic study confirmed the diagnosis of PXE identifying two ABCC6 mutations in the composite state in the boy: the c.2263G> A (p.G755R) mutation on exon 18 and the c.3421C> T (pR1141X) mutation on exon 24 and the 4021G> A (R1164Q) mutation in the homozygous state of ABCC6 exon 24 in the girl. CONCLUSION: Digestive manifestations are unusual ; however, pseudoxanthoma elasticum should be considered in all cases of gastrointestinal bleeding for no apparent reason. Early diagnosis allows prevention and measures to control the risk factors and limit the progression of complications.

[Rotary C1-C2 dislocation: a case report]. / La luxation rotatoire C1-C2 : à propos d'une observation.

The atloid-axoid rotatory slipped disc is a rare pathology with still uncertain etiology. Many situations can be factors of this disease. We report a case in a child who was admitted to the hospital for a stiff neck that had been evolving for 1 month. The clinical examination found an irreducible angular deformity of the neck and multiple cervical adenopathies. The ORL examination was normal, the biological tests showed no disorders, and the X-ray examinations were also normal. Unexpected admission features were also disconcerting. The child suddenly presented a stiff neck on waking 2 days after a traditional circumcision at home, which might have been traumatizing. The mother also reported fever a few days before, attributed to rhinopharyngitis. Before his referral to the Rabat Children's Hospital, the child had received an anti-inflammatory treatment without any improvement. He had also been considered to have an opisthotonos on admission and was treated for suspected tetanus. Finally, the rotatory dislocation of C1-C2 was suggested, and a cervico-occipital junction scanner with three-dimensional reconstructions confirmed the diagnosis. The child was treated with cranial traction with good progression. This case opens the discussion of this rare disease, often unrecognized, which requires a multidisciplinary approach.

[Sclerosing cholangitis revealing Langerhans cell histiocytosis in a 15-month-old child]. / Cholangite sclérosante révélatrice d'une histiocytose langerhansienne chez un nourrisson de 15 mois.

INTRODUCTION: Langerhans cell histiocytosis (LCH) is a rare disease that mainly affects young children. Sclerosing cholangitis may occur in 10-15% of patients with the multivisceral form. We report the case of a 15-month-old child who presented sclerosing cholangitis revealing LCH. OBSERVATION: A 15-month-old child was hospitalized for cholestatic jaundice. He was the son of consanguineous parents and had repeated ear infections. One month before his hospitalization, he developed febrile jaundice. Initial clinical examination showed hepatosplenomegaly, with cholestasis, bicytopenia, and biological inflammatory syndrome. The digestive radiological studies revealed hepatomegaly and a regular thickening of the intestinal wall with an extension to the biliary tree. During his hospitalization, the infant developed stubborn ascites, lymphadenopathy, and skin lesions. Skull radiographs revealed punched-out lesions. The skin biopsy confirmed the diagnosis of histiocytosis X. Chemotherapy was started. The child died after the first course of treatment as a consequence of liver failure. CONCLUSION: Sclerosing cholangitis may complicate LCH, mainly in its multivisceral form. On average, sclerosing cholangitis develops 2 years after diagnosis in children. It is rarely indicative of the diagnosis, which is mainly based on radiological examinations. Liver involvement is a factor of poor prognosis. It precipitates the occurrence of biliary cirrhosis. Usually, sclerosing cholangitis responds poorly to Langerhans histiocytosis treatment and liver transplantation must be considered.

Cornstarch thickened formula reduces oesophageal acid exposure time in infants.

BACKGROUND: Infant regurgitation is a phenomenon causing worldwide parental distress and anxiety. Parental reassurance and dietary advices regarding feeding techniques and volumes are helpful in the management. Guidelines also recommend the use of thickened formula. However, the impact of thickened feeding on the frequency of acid reflux is still a matter of debate. Therefore, we evaluated the effect of a casein predominant formula thickened with a specifically selected and treated cornstarch on the frequency and duration of acid reflux episodes. METHODS: Ninety-six formula-fed infants with a mean age of 93 days, presenting with episodes of regurgitation and vomiting occurring more than five times a day and with an abnormal oesophageal pH monitoring, were randomised to a regular infant formula (n = 45) or cornstarch thickened casein predominant formula (n = 51) for 28 days. A second pH monitoring was performed at the end of the study period (26+/-5 days). Symptoms were daily recorded in a diary by the parents for 28 days. RESULTS: At inclusion, the pH-metric parameters did not differ between the control and the intervention group. Results of pH monitoring at baseline and at the end of the study did not differ in the control group on the regular infant formula. However, in the group with the casein dominant cornstarch thickened formula, all pH-metric parameters (reflux index (% of the investigation time with a pH < 4.0), number of reflux episodes >5 min, duration of the longest reflux episode) decreased significantly. The frequency of vomiting and regurgitation did not differ between both groups at baseline, remained unchanged in the control group, but decreased significantly in the intervention group. CONCLUSION: A casein dominant formula thickened with a specifically treated cornstarch reduces oesophageal acid exposure, and reduces the frequency of clinical symptoms.

The effect of fermented milk on interferon production in malnourished children and in anorexia nervosa patients undergoing nutritional care.

For several years cytokine production has been associated with infections but it was not suspected that some types of food could also induce cytokines, even in a state of non-infection. Lactic bacteria can induce interferon (IFN) production in human healthy subjects, thus, a better protection against infections would be expected. Therefore, we planned to evaluate the effect of two diets including yoghurt or milk on IFN-gamma production during nutritional recovery in two different situations of malnutrition: (1) children with diarrhoea; and (2) patients with anorexia nervosa (AN). Both the diet including yoghurt of that including milk seemed to increase IFN-gamma production at the end of nutritional recovery in the malnourished children with diarrhoea. The significance of interferon production and the lymphocyte subset increase should be explored to know if a better resistance against pathogens is related to them. Regulation of intestinal absorption and moderate stimulation of interferon production make the yoghurt-based diet a good choice in the nutritional care of children. In the same way, an increase in the IFN-gamma production was observed in AN patients consuming yoghurt. This increase of IFN-gamma production could be considered a biological marker to detect the effect of probiotics on the immune response, especially in the improvement of a deficient nutritional status.

[Mucopolysaccharidosis type I in Morocco: clinical features and genetic profile]. / Mucopolysaccharidose de type I au Maroc: manifestations cliniques et profil génétique.

BACKGROUND: Mucopolysaccharidoses (MPS) are inherited metabolic disorders due to lysosomal enzyme deficiencies, leading to glycosaminoglycan accumulation in lysosomes of different tissues. The aim of this study was to characterize MPS types, particularly MPS I, which are difficult to differentiate by clinical features. PATIENTS AND METHODS: Over a period of three years (June 1996-May 1999), 16 Moroccan patients (3-20 years old) with MPS were investigated. Twelve of them came from the Souss region. In subjects with suspected clinical MPS I or II, the diagnosis was confirmed by biochemical investigations, which included the quantification of total glycosaminoglycans (GAGs) released in urine, their identification, and the assay of alpha-L-iduronidase activity in leucocytes. A molecular analysis was performed in parallel, to provide the genetic proof of the diagnosis. RESULTS: These 16 patients belonged to 12 families, nine of which were consanguineous (75%). Twelve patients had Hurler syndrome and three had Hurler/Scheie's syndrome; no case of Scheie's syndrome was observed. Short stature, coarse face, organomegaly, hernia, cardiac disease, mental delay and dysostosis were observed in variable degrees. We report three cases without corneal clouding. Increased total urinary GAGs, identified as dermatan sulfate and heparan sulfate by thin-layer chromatography and total deficiency of alpha-L-iduronidase activity, were noted in studied subjects. At the molecular level the P533R mutation was detected in 24 among 26 alleles studied. CONCLUSION: It is now possible to perform the screening of MPS I and II in Morocco by analysis of clinical, radiologic observations and biological investigation. The predominance of P533R mutation could permit the screening of healthy heterozygotes and genetic counselling for families of Moroccan descent.

[Visceral leishmaniasis and malnutrition: a case report]. / Leishmaniose viscérale et malnutrition: à propos d'une observation.

BACKGROUND: Visceral leishmaniasis occurring in malnourished subjects can have an uncommon course, which explains difficulties in its diagnosis. CASE REPORT: A 22-month-old infant was admitted because of malnutrition and prolonged fever. The bacteriological investigation was negative. When his nutritional status improved, he developed a splenomegaly. The medullogram confirmed the diagnosis of visceral leishmaniasis. The course was then favorable with treatment by pentavalent antimonial. CONCLUSION: Malnutrition constitutes a risk factor of opportunist parasitic disease such as leishmaniasis. Its diagnosis can be very difficult.

[A severe form of urinary tuberculosis in children]. / Forme grave de la tuberculose urinaire chez l'enfant.

Urinary tuberculosis is a rare disease in children. It poses major diagnostic problems because of clinical symptoms, which are often atypical and misleading. It causes serious lesions which are often multifocal and extensive, requiring complex surgical excision and urinary tract reconstruction. Prevention of this disease is based on generalized vaccination with BCG and adequate treatment of pulmonary tuberculosis. The authors report a case of urinary tuberculosis in a fourteen-year-old child who presented episodes of cystitis and hematuria refractory to treatment. The diagnosis, confirmed by the positive test for AFB in the urine was established late, at the stage of silent kidney and scleroatrophic bladder. The patient was treated with antituberculous chemotherapy (Isoniazid; Rifampicin, PZA) and nephro-ureterectomy with augmentation enterocystoplasty.