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Background. Mitochondrial respiratory chain (RC) disorders are a growing group of disorders with a large variety of clinical presentations ranging from well-defined clinical syndromes to nonspecific manifestations, such as failure to thrive, exercise intolerance and seizures.Objective. To describe the clinical, biochemical, and histochemical spectrum of 38 Egyptian patients clinically suspected of havingmitochondrial RC disorders.Methods. A total of 38 patients (female, n=18 (47.4%); male, n=20 (52.6%)) clinically suspected of having mitochondrial diseases had been referred to the Inherited Metabolic Diseases Laboratory at Cairo University Children’s Hospital. Laboratory investigations and analyses included histochemical staining of cytochrome c oxidase and succinate dehydrogenase in muscle biopsies, as well as spectrophotometric assays of RC complexes in muscle homogenates.Results. Twenty-three patients (60.5%) were diagnosed with different RC enzyme deficiencies. Fifteen patients (65%) had complex Ideficiency and all of them also had lactic acidosis (mean (standard deviation)) plasma lactate concentration of 4 (1.65) mmol/L). Twopatients (9%) with marked complex IV deficiency both showed COX-negative ragged red fibers (RRFs) on histochemical staining.Combined complex I and complex II deficiency with scattered COX-stain deficiency and RRFs was diagnosed in 2 patients (5.25%), whilea further 2 patients (5.26%) had combined (complex I, II+III, complex IV) deficiencies. Isolated complex II deficiency was diagnosed in2 patients (5.26%) and 15 (39.5%) patients had normal RC enzyme activities.Conclusion. Biochemical assay of RC complexes is considered the cornerstone for diagnosis of RC complex mitochondrial disorders.These disorders are common among Egyptian paediatric patients.

Mitochondrial neurogastrointestinal encephalopathy: clinical, biochemical and molecular study in three Egyptian patients:Background: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare autosomal recessive disorder. The disease is caused by mutations in the thymidine phosphorylase gene. This article reports the clinical, biochemical and molecular findings in three Egyptian patients with Mitochondrial Neurogastrointestinal Encephalopathy syndrome from two different pedigrees.Subjects and Methods: The three patients were subjected to thorough neurologic examination, Brain Magnetic Resonance Imaging. Histochemical and biochemical assay of the mitochondrial respiratory chain complexes in muscle homogenate was performed (1/3). Thymidine Phosphorylase enzyme activity was performed in 2/3 patients and Thymidine Phosphorylase gene sequencing was done (2/3) to confirm the diagnosis.Results: All patients presented with symptoms of severe gastrointestinal dysmotility with progressive cachexia, neuropathy, sensory neural hearing loss, asymptomatic leukoencephalopathy. Histochemical analysis of the muscle biopsy revealed deficient Cytochrome C oxidase and mitochondrial respiratory chain enzyme assay revealed isolated complex I deficiency (1/3). Thymidine Phosphorylase enzyme activity revealed complete absence of enzyme activity in 2/3 patients. Direct sequencing of Thymidine Phosphorylase gene revealed c.3371A>C homozygous mutation. Molecular screening of both families revealed heterozygous mutation in both parents and 4 siblings.Conclusions: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare mitochondrial disorder with an important diagnostic delay. In case of pathogenic mutations in Thymidine Phosphorylase gene in the family, carrier testing and prenatal diagnosis of at risk members is recommended for early detection. The possibility of new therapeutic options makes it necessary to diagnose the disease in an early state.