Stroke due to mitochondrial disorders in Saudi children

To report on the clinical and biochemical features of patients who presented with stroke due to mitochondrial disorders amongst a prospective and retrospective cohort of Saudi children. Children, who presented with stroke, were evaluated at the Division of Pediatric Neurology, or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia, during the periods July 1992 to February 2001 [retrospective study] and February 2001 to March 2003 [prospective study]. Open muscle biopsies were obtained from patients suspected to have mitochondrial disorders, and examined using conventional histological and histochemical techniques. Biochemical, molecular pathological investigations, or both, of muscle could be arranged for only some of the patients. Mitochondrial disorders were the underlying risk factor for stroke in 4 [3.8%] of 104 children [aged one month to 12 years]. Three patients [one male and 2 females] had Leigh syndrome [LS] and one had mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes [MELAS]. At the time of stroke, the 3 children with LS were 11 months, 15 months, and 7 years old. They presented with psychomotor regression and seizures. Muscle histology and histochemistry showed mild non-specific changes but no ragged red fibers. Biochemical analysis of muscle [in one patient] revealed deficiency of pyruvate dehydrogenase complex. Analysis of mitochondrial DNA [mtDNA], [the other 2 patients] was negative for the 2 point mutations [T-G and T-C] at nucleotide position 8993, and for two T-C point mutations [at positions 8851 and 9176 of the ATPase 6 gene] that have been described in patients with LS. The girl with MELAS syndrome presented with a stroke-like episode at the age of 29 months and had focal brain lesions in the medial aspect of the left occipital and temporal lobes, and in the posteromedial aspect of the left thalamus, which resolved within 7 weeks. She had raised cerebrospinal fluid lactate but no ragged red fibers on muscle histochemistry. Biochemical assay of muscle homogenate showed reduction in respiratory chain complexes I, III and IV. Mutation screening of mtDNA at nucleotides 3243 [tRNA Leu[UUR] and 8344 [tRNA Lys] was negative. Mitochondrial disorders constitute a risk factor for stroke in Saudi children. However, demanding and highly specialized investigations are needed to confirm the diagnosis. These are better performed at supraregional centers where facilities for clinical, biochemical and molecular work-up are available

Morphologic patterns of male infertility in Saudi Arabia

To determine the predominant histopathological patterns seen in the testicular biopsies taken during the investigation of male infertility and to compare the obtained histopathological findings with those seen in other similar studies. This is a retrospective study performed on 230 testicular biopsies which were examined in the Department of Pathology at King Khalid University Hospital in Riyadh over a period of 10 years. The histopathological findings were grouped into 8 different morphologic categories. We have utilized a classification that is principally morphologic but that uses known or suspected clinical associations in the case of karyotypic abnormalities and excurrent duct obstruction. Of the total of 230 testicular biopsies studied, 72 cases showed normal spermatogenesis, of which 50 cases were suspected to be associated with excurrent duct obstruction. Germinal cell aplasia with and without focal spermatogenesis was found in about 90 cases. Thirty cases showed hypospermatogenesis, 25 cases showed maturation arrest and 12 cases showed end stage tubular sclerosis with interstitial fibrosis. Only one case was noted to show features associated with karyotypic abnormalities. A higher percentage of germinal cell aplasia was noted in this study when compared with other similar investigations including one previous local study. Possible causes of these discrepancies may be related to several factors including environmental effects. The design of the different studies and the criteria used for patient selection or both could also explain the cause of these observed differences

Prevalence of intratubular germ cell neoplasia of the testis

Intratubular germ cell neoplasia has been described as a premalignant state with the potential to progress to invasive carcinoma of the testis. We determined the prevalence of intratubular germ cell neoplasia in relation to the associated pathology in testicular biopsies from infertile men and in orchidectomies performed for both neoplastic and non-neoplastic conditions. We reviewed all testicular biopsies performed for the investigation of infertility and orchidectomy specimens of non-neoplastic conditions and testicular tumors seen during a period of 10 years at King Khalid University Hospital. Histopathological examination of all specimens to determine the presence of intratubular germ cell neoplasia was carried out. Immunohistochemistry for placenta alkaline phosphatase was performed on formalin-fixed and Bouin's-fixed specimens with intratubular germ cell neoplasia, positive and negative controls were also stained for comparison. The review included a total of 548 male patients. The incidence of intratubular germ cell neoplasia in 244 testicular biopsies from infertile men was 0.82%. The percentage of intratubular germ cell neoplasia seen in 17 orchidectomies performed for invasive germ cell tumors was, however, 47%. Intratubular germ cell neoplasia was not detected in 109 of the orchidectomies performed for maldescended testes and in 2 cases of the androgen insensitivity syndrome. All cases of intratubular germ cell neoplasia identified in this review were not described at the time of primary pathological examination of the biopsies and orchidectomy specimens. Awareness of this clinicopathological entity is essential to describe and detect this form of testicular cancer at the preinvasive state. The prevalence of intratubular germ cell neoplasia is low in Saudi patients particularly in the high risk group of patients with cryptorchidism. Furthermore, our results do not support the need for routine biopsy of the testis of infertile or cryptorchid patients unless sampling is indicated in preparation of assisted fertilization technique or orchidopexy