T. Kamoun

A Novel Nonsense Mutation in HSD17B3 Gene in a Tunisian Patient with Sexual Ambiguity

INTRODUCTION 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) isoenzyme is present almost exclusively in the testes and converts delta 4 androstenedione to testosterone. Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46,XY Disorders of Sex Development (46,XY DSD). AIM This study aimed to present the clinical and biochemical features of a Tunisian patient who presented a sexual ambiguity orienting to HSD17B3 deficiency and to search for a mutation in the HSD17B3 gene by DNA sequencing. METHODS Polymerase chain reaction (PCR) amplification and subsequent sequencing of all the coding exons of HSD17B3 gene were performed on genomic DNA from the patient, her family, and 50 controls. RESULTS Genetic mutation analysis of the HSD17B3 gene revealed the presence of a novel homozygous nonsense mutation in the exon 9 (c.618 C>A) leading to the substitution p.C206X. The mutation p.C206X in the coding exons supports the hypothesis of HSD17B3 deficiency in our patient. CONCLUSION The patient described in this study represented a new case of a rare form of 46,XY DSD, associated to a novel gene mutation of HSD17B3 gene. The screening of this mutation is useful for confirming the diagnosis of HSD17B3 deficiency and for prenatal diagnosis.

Ganglioneuroma of adrenal gland in a patient with Turner syndrome

A 15-year-old girl with Turner syndrome was unexpectedly found to have a left suprarenal mass. Extensive investigations showed a clinically and biochemically inapparent mass. Computed tomography disclosed a well-defined solid lesion in the left adrenal measuring 6.5 x 5 cm with minimal contrast enhancement. Laparoscopic adrenalectomy was done. Histologic examination revealed an encapsulated mass originated from the left adrenal medulla. Tumor tissue comprised abundant collagen fibers and spindloid cells admixed with mature ganglion cells. The tumor was diagnosed as left adrenal ganglioneuroma. According to literature, we report the eighth case of ganglioneuroma complicating Turner syndrome. Patients with this syndrome are predisposed to the development of neuroblastoma and related tumors. Reasons for this predisposition might relate to genetic and hormonal factors. Given that these tumors are often limited stage and of good prognosis, we recommend their screening in all patients with Turner syndrome.

Hemolytic Anemia and Metabolic Acidosis: Think about Glutathione Synthetase Deficiency

Glutathione synthetase deficiency (GSSD) is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with hemolytic anemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low glutathione synthetase activity in erythrocytes or cultured skin fibroblasts. The prognosis seems to depend on early diagnosis and treatment. We report a 4 months old Tunisian male infant who presented with severe metabolic acidosis with high anion gap and hemolytic anemia. High level of 5-oxoproline was detected in her urine and diagnosis of GSSD was made. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. He died of severe metabolic acidosis and sepsis at the age of 15 months.

Hemolytic Anemia and Progressive Neurologic Impairment: Think About Triosephosphate Isomerase Deficiency

We have reported the first Tunisian case of triosephosphate isomerase (TPI) deficiency in a 2-year-old girl. She was the first child of a nonconsanguineous couple. The disease included a neonatal onset of chronic hemolytic anemia, recurrent low-respiratory infections then progressive neurological involvement. The diagnosis was made after her death from the TPI values of her parents who exhibited intermediate enzyme deficiency. Molecular study of TPI genes showed that the father and the mother are heterozygous for Glu105Asp mutation. Pediatricians must be alert to the differential diagnosis in patients having hemolytic anemia and other concomitant manifestations.

Arterial ischemic stroke in children: 22 cases from southern Tunisia

The aim of this study is to review the cases of arterial ischemic stroke (AIS) in children in our department to evaluate the clinical and neuroimaging features, the etiologies and the treatment. This study retrospectively reviewed the records of all children aged between 1 month and 16 years who were admitted from 2000 to 2010 for AIS in the pediatrics department of Hedi Chaker University hospital in Sfax, Tunisia. Twenty-two children were enrolled. The average age at stroke was 3 years and 2 months. Cardiac disease (27%) and moyamoya disease (18%) were the most common etiologies. Adverse outcome after childhood stroke includes death in 9%, recurrence in 18% and neurologic deficits in 45%.

Nephropathic infantile form of cystinosis about one case.

Cystinosis is the major cause of inherited Fanconi syndrome, and should be suspected in young children with a failure to thrive and with signs of renal proximal tubular damage. This is a study of a case report of cystinosis revealed by a growth failure and chronic dehydration. A 9-month-old boy was referred to our department for evaluation of polyuria and polydipsia. Clinical examination showed dehydration and enlarged wrists and rachitic rosaries. The presence of metabolic acidosis, hypokalemia, hypochloremia with proteinuria, polyuria, and hypercalciuria was suggestive of inherited Fanconi syndrome. The diagnosis of cystinosis was confirmed by an increased leukocyte cystine level.

Érythroblastopénie aiguë secondaire à une infection par le Parvovirus B19 révélant une sphérocytose héréditaire chez 2 enfants de la même famille.

Acute Parvovirus B19 infection is responsible for blocking the erythroblastic line, usually with no consequences on hematopoiesis except in patients with chronic hemolytic anemia in whom it can evolve to potentially serious acute anemia. We report 2 observations of acute erythroblastopenia revealing hereditary spherocytosis in 2 children (1 boy and 1 girl) of non-consanguineous parents.

Le syndrome des antiphospholipides à propos d’une nouvelle observation pédiatrique

UNLABELLED Many conditions can lead to cerebral strokes in children. The antiphospholipid syndrome widely described in adults in association with systemic lupus erythematosus, is rare in childhood. CASE REPORT Two months after recovering from varicella and a few days after an episode of bronchitis, a 17-month-old girl developed left facial paralysis associated with right hemiplegia. Brain MRI and angio-scan showed thrombosis in the internal left carotid associated with ischemia in the superficial posterior territory of the left Sylvian artery. Echocardiography and hemoglobin electrophoresis were normal. Tests were negative for protein S, C and antithrombin III deficiencies and no resistance to activated protein C. IgM anticardiolipin antibodies were detected at high level (greater than 25IU/l) initially and six weeks later. In the absence of an evident etiology, mainly systemic lupus erythematosus (negative antinuclear antibodies), the diagnosis of primary antiphospholipid syndrome was retained. The girl was treated by heparin then by salicylate at antiaggregate doses associated with re-habilitation. Twelve months later, the patient had not developed any other thrombosis, in spite of a high level of anticardiolipin antibodies. CONCLUSION In children with cerebral strokes, antiphospholipid syndrome must be discussed when the usual etiologies have been ruled out.

Van Wyk–Grumbach syndrome: A rare cause of precocious puberty

Introduction Profound primary hypothyroidism in children causes generally delayed pubertal development. Rare association with precocious puberty may occur especially in long standing untreated patients. The cardinal features of hypothyroidism inducing isosexual precocious puberty include thelarche, galactorrhea and/or menarche. Other characteristics features are the absence of sexual hair and retardation of linear growth [1,2]. This condition was described in 1960 by Van Wyk–Grumbach in a report of three cases of long standing hypothyroidism, presented with menarche, premature thelarche and galactorrhea [3]. We report an 8 year-old-girl who presented with vaginal bleeding and short stature. Subsequent investigations led to a diagnosis of autoimmune hypothyroidism.

Fulminant mulch pneumonitis in a previously healthy child

Chronic granulomatous disease (CGD) is associated with multiple and recurrent infections. In patients with CGD, invasive pulmonary infection with aspergillus species remains the greatest cause of mortality. Acute fulminant presentations of fungal pneumonia are catastrophic. It is a medical emergency, and currently the treatment is based on association of corticosteroids and antifungal therapy. We describe the case of an 11-year-old boy, with late initial presentation of CGD, which was revealed by fulminant aspergillus pneumonia. He was successfully treated with an association of high doses of steroids and voriconazole.