Clinical and molecular findings in eight Egyptian patients with suspected mitochondrial disorders and optic atrophy

Mitochondrial respiratory chain disorders [RCD] are a group of genetically and clinically heterogeneous diseases, caused due to defects of the respiratory chain. This study aimed to investigate the presence of common mtDNA point mutations in tRNALeu [UUR], tRNALys, MT-ATPase 6, MT-ND4, MT-ND1, MT-ND6 genes in eight Egyptian patients suspected to have mtDNA disease and optic atrophy. PCR-RFLP analysis was done for the detection of 3243A > G, 327IT > C, 8344A > G, and 8993T > G/C mtDNA point mutations. DNA direct sequencing was pursued for the detection of 11778G > A, 3460G > A and 14484T > C mtDNA point mutations. No point mutation of 3243A > G, 327IT > C, 8344A > G, and 8993T > G/C was detected in our group of patients. Four mtDNA polymorphisms in MT-ND1 and MT-ND4 genes [11467A > G, 11719G > A, 3348A > G and 3357G > A] were detected in three patients. Mitochondrial disorders are caused by a variety of genetic and racial factors, which differ among populations. The negative results of this study indicate that the chosen mutations might not be specific in Egyptians. Another explanation might be due to the low heteroplasmic levels of the mtDNA mutation. A registry for the different mtDNA mutations in Egyptian patients is highly recommended

Sexual dysfunction in males with hepatitis C virus: relevance to histopathologic changes and peginterferon treatment

The frequency of sexual dysfunction [SD] is not well known in patients with chronic hepatitis C virus [HCV]. In spite of the fact that histological benefits of peginterferon [Peg-IFN]/ribavirin therapy are well established, the effects on sexual health are less certain. To assess the prevalence of the SD and explore its relevance to histopathologic changes and Peg-IFN treatment. The study included 100 HCV males; all the patients completed questionnaires to assess their sexual function before and during the treatment. Before treatment, SD was reported only by 12 [19.4%] and 10 [29.4%] patients of early and advanced liver fibrosis, respectively. SD during HCV treatment [with Peg-IFN and ribavirin] for liver fibrosis was significant, as 24 [70.6%] out of 34 [100%] of HCV patients had advanced fibrosis but only 20 [32.3%] out of 62 [100%] patients had early fibrosis and were sexually affected [P = 0.01]. SD before treatment was found in 22 [22%] patients; 16 [16%] were >40 years old and 6 [6%] patients were

Hepatitis C virus infection and gene expression of hepatocellular carcinoma in Egyptian patients

Gene expression profiling of hepatocellular carcinoma [HCC] is promising for refining the diagnosis and prognosis as well as identifying potential therapeutic targets. Our study aimed to study the gene expression in 40 HCC patients infected with hepatitis C virus [HCV] using RT-PCR technique on surgical liver sample. Gene expression changes in HCV-positive group were compared with gene expression in HCV-negative group. Four genes were included in this study, AFP gene, CD10 gene, HGF gene and GRB2 gene. The expression of the four genes were slightly higher in HCV positive group than in HCV negative group, however, the difference between the two groups was non-significant. HGF gene was expressed in only 20% of HCC patients and GRB2 gene was expressed in 95% of HCC patients. AFP gene and CD10 gene were expressed in all patients. AFP gene, CD10 gene and GRB2 gene play an important role as diagnostic markers of HCC

Predictive value of biochemical markers in pregnancy induced hypertension

Hypertensive disorders of pregnancy complicate 10% of all pregnancies. They include gestational hypertension, preeclampsia, eclampsia, and chronic hypertension. The aim of this study was to identify predictive markers for early diagnosis of women who are at risk of gestational hypertension or preeclampsia. This study was conducted on a total of 64 cases. Twenty nine were pregnant females who developed pregnancy induced hypertension and 35 females were normotensive throughout pregnancy with normal pregnancy outcome taken as controls. Subjects were recruited from the Prenatal Diagnosis Clinic, at the National Research Center. Maternal blood samples were taken as part of the department's routine second trimester biochemical screening program at 14- 20 weeks gestation. All cases were subjected to the estimation of human chorionic gonadotropin [hCG], tumor necrosis factor alpha [TNF- alpha], C-reactive protein [CRP], nitric oxide [NO] and the lipid peroxidation product malondialdehyde [MDA], in addition to the estimation of lipid profiles [cholesterol [Ch], high density lipoprotein cholesterol [HDLc], low density lipoprotein cholesterol [LDLc] and triglycerides [TG]], urea and creatinine. The study showed significant increase of [beta-hCG, TNF-alpha, CRP, MDA, urea, creatinine, TG, Ch and LDLc in women who developed PIH compared with normotensive pregnant women, while NO was significantly decreased in women who developed PIH compared with normotensive pregnant women. It could be concluded that the elevated levels of TNF-alpha, beta-hCG, CRP and MDA, in addition to decreased levels of NO and abnormal lipid profiles were implicated in subsequent risk for PIH. Furthermore TNF-alpha and MDA may be considered as important predictive markers for early detection of PIH

therapeutic role of vitamin E and C on non syndromic sensorineural hearing loss

Antioxidants help in preventing further degeneration or possibly even reverse degenerative processes after they have been activated. Free radical scavengers, such as vitamin E and vitamin C, protect inner ear from oxidative damage. To evaluate the efficacy of two classes of agents found effective in preventing sensorineural hearing loss [antioxidants and low fat diet] and determine if it can improve the degree of hearing loss by preventing oxidative damage. fifty four patients were divided into two groups, twenty four patients were given vitamin E and C for two months and thirty patients were given low fat diet [without animal fats] for two months. Auditory function was monitored along with plasma concentrations of Beta carotene, vitamins A, E and C and lipid peroxidation. Also, zinc, copper, calcium, phosphorus and magnesium together with immunoglobulin G, M and A levels were estimated before and after treatment. Significant increase in antioxidants and decrease in lipid peroxidation was observed in the group which was given vitamin E and C. The addition of antioxidants significantly enhanced the evoked responsiveness over that observed with the low fat diet group indicating a putative role of antioxidants in the pathogenesis of sensorineural hearing loss. The findings showed that supplemental dietary antioxidant may have a beneficial role in the prevention of deafness. It also proved a relationship between low fat diet and improvement of hearing loss

Oxidative stress in nonsyndromic sensorineural hearing loss

Ototoxicity seems to result from the inhibition of cochlear antioxidant defenses, causing an increase in the amount of reactive oxygen species. These findings suggest a causal relationship between the formation of reactive oxygen species, oxidative stress and functional/morphological ear damage. auditory function was monitored along with plasma concentrations of copper, zinc, calcium, phosphorus, magnesium and iron. Further more, lipid peroxidation, beta carotene, vitamin A, E and C activities and immunoglobulin G, M and A levels were estimated. A significant decrease in calcium, phosphorus, beta carotene, and vitamin E activities as well as low levels of immunoglobulin G and M were found. The observed increase in lipid peroxidation is indicative for oxidative stress which suggests a putative role of antioxidants in the pathogenesis of sensorineural hearing loss. Conclusion: The results support the hypothesis that dietary and immune factors influence individual susceptibility to hearing loss. Further studies are needed to verify whether antioxidants, correction of deficient nutrients and/or immune modulation would improve sensorineural hearing loss

effect of diet on antioxidant status in patients with galactosemia

Galactosemia is an autosomal recessively inherited disorder of galactose metabolism. It has good prognosis, if detected in neonatal period or early infancy. Treatment consists of life long dietary restriction of galactose. Present study included eight patients with galactosemia on dietary treatment, five of them had galactose-1-phosphate uridyltransferase deficiency known as classical galactosemia and three had uridine-diphosphate galactose-4' epimerase deficiency. Clinical evaluation of patients under galactose restricted diet and assessment of the antioxidant status in response to dietary therapy was done. Delayed milestones were present in all patients, jaundice at birth was present in 4 and low birth weight was present in 3 patients. Craniofacial dysmorphism was present in 5 patients. Hepatomegaly was present in 6 patients. MRI of the brain showed brain atrophy in 3 patients and demyelination in 2 patients. There was cataract in 7 patients. The levels of zinc, copper, iron, calcium, phosphate, magnesium, selenium, manganese, beta-carotene and vitamin A were evaluated in the blood of galactosemic patients on galactose restricted diet and a comparison between trace elements, beta-carotene and vitamin A in studied patients with galactosemia and controls was done. Copper, calcium, phosphate, manganese and beta-carotene levels in blood were significantly decreased in our patients [p<0.001] than in controls. These findings suggest that patients on galactose restricted diet are at risk of oxidative stress. The data emphasize the importance of dietary supplementation with an antioxidant containing beta-carotene, calcium, copper, selenium and manganese to inhibit oxidative stress in these patients. Consequently this will minimize the neurological deficits improve bone mineralization, reduce the development of retinopathy and damage to liver cells in patients with galactosemia

effect of diet on antioxidant status in patients with galactosemia

Galactosemia is an autosomal recessively inherited disorder of galactose metabolism. It has a good prognosis, if detected in neonatal period or early infancy. Treatment consists of life long dietary restriction of galactose. Our study included eight patients with galactosemia on dietary treatment, five of them had galactose-1-phosphate unidyltransferase deficiency known as classical galactosemia and three had uridine-diphosphate galactose-4' epimerase deficiency. Delayed milestones were present in all patients, jaundice at birth was present in 4 and low birth weight was present in 3 patients. Craniofacial dysmorphism was present in 5 patients. Hepatomegaly was present in 6 patients. MRI of the brain showed brain atrophy in 3 patients and demyelination in 2 patients. There was cataract in 7 patients. The aim of this study was to asses the antioxidant status in response to dietary-therapy. The levels of zinc, copper and Iron, calcium, phosphate, magnesium, selenium, manganese, beta-carotene and vitamin A were evaluated in the blood of galactosemic patients on galactose restricted diet. Also, a comparison between trace elements, beta-carotene and vitamin A in studied patients with galactosemia and controls was done. Copper, calcium, phosphate, manganese and beta-carotene levels in blood were significantly decreased in our patients [p<0.001] than in controls. These findings suggest that treated galactosemic patients are at risk of oxidative stress and abnormal bone mineralization. Therefore, therapeutic intervention in these cases should be more appropriately targeted. The data emphasise the importance of antioxidants and trace elements in minimizing the neurological deficits in galactosaemic patients

Clinical and biochemical changes in Egyptian patients with Sjogren Larsson syndrome

The Sjogren-Larsson syndrome [SLS] is an inborn error of lipid metabolism, characterized clinically by congenital ichthyosis, mental retardation and spasticity. It is a rare autosomal recessive condition resulting from fatty aldehyde dehydrogenase deficiency, which is involved in lipid synthesis and catabolism. This study included nine patients with SJL, their ages ranged from 2.6 to 12 years [6.4 +/- 2.2]. All the patients were subjected to full clinical examination and biochemical investigations including the estimation of the level of fatty aldehyde dehydrogenase in leucocytes and total cholesterol, triglycerides, low-density lipoproteins [LDL], high-density lipoproteins [HDL], low-density lipoprotein oxidizability and 5-lipooxygenase in plasma. Neurophysiologic examinations including magnetic resonance image [MRI], electro encephalogram [EEG], and visual evoked potential [VEP] were done. The study aims to outline the clinical signs and symptoms together with the biochemical characteristics of SLS. Our findings provide evidence for defective 5-lipoxygenase degradation, fatty aldehyde dehydrogenase deficiency, while lipid profile and low density lipoproteins oxidizability were significantly increased in SLS patients. These findings suggest that fatty aldehyde dehydrogenase plays a major role in detoxification and in the turn over of fatty aldehydes and lipids and offer non-invasive diagnostic tools. Moreover, they provide a powerful rationale for therapeutic trials aimed at inhibiting 5-lipoxygenase synthesis

Maternal vitamin B12 and the risk of fetal neural tube defects

Folic acid insufficiency is a known risk factor for neural tube defects [NTDs], while the role of vitamin B12 is questionable. Thus, our purpose was to investigate if low maternal serum vitamin B12 is associated with an increased risk of NTDs. Prenatal Diagnosis and Clinical Genetics Clinics, National Research Center, in collaboration with the Radioisotope Department, Nuclear Research Center. The study groups included 36 women who were, or had been, pregnant with a NTD-affected fetus. The control groups comprised 35 healthy women with normal prior or current pregnancy and uncomplicated obstetric histories. Fasting plasma homocysteine, serum folate and cobalamin [vitamin B12] were performed. Odds ratio [OR] and 95% confidence intervals were calculated. The fasting homocysteine was significantly higher in the study groups as compared to the controls. The median serum folate concentrations were similar in cases and controls. While the median vitamin B12 concentrations were significantly lower in the study groups compared to the controls. Low vitamin B12 concentration was associated with an approximately 2 to 3 fold increased risk for NTDs. Low maternal serum of vitamin B12 can be considered an important etiologic factor for the development of neural tube defects in our population. This may help in both genetic counseling for families with history of NTDs malformation, and as a preconceptional prophylactic measure by maternal supplementation of vitamin B12 and folic acid

Hereditary non-syndromic hearing loss: influence of different variables

Non-syndromic hearing loss [NSHL] was studied in twenty-five patients using a clinical, audiological, cytogenetic and neurobiochemical evaluation. The study group was divided into five subgroups according to severity of hearing loss. Positive parental consanguinity was present in 84% of cases and similarly affected family members were present in 76%. All patients had no congenital malformations and were not dysmorphic. Patients possibly exposed to environmental factors were excluded from the study. Abnormal karyotyping was present in three cases, one case showed chromosome 15p 4, another case showed chromosomal del 11q22.1 and in the third case [47,XY] there was marker chromosome 15. Fluorescence in situ Hybridization [FISH] technique was performed on the case which showed marker. The study group showed significant lowering of five plasma amino acid levels [glutamic acid, aspartic acid, histidine, 3-methylhistidine and carnosine]. There was significant correlation between severity of hearing loss and each of the following: patient's age, glutamic acid, aspartic acid, 3-methylhistidine and carnosine. Identification of NSHL early after birth, as well as, amino acid screening is essential, to allow for faster therapeutic intervention and proper genetic counseling

Peroxisomal disorders in Egyptian children estimation of very long chain fatty acids by GC/MS

In this study, the biochemical quantification of very long chain fatty acids [VLCFAs] verified the diagnosis of peroxisomal disorders in 25 out of 30 clinically suspected patients, their ages ranged from 3 months to 18 years. The control group consisted of ten healthy children matched for age and sex. All patients were subjected to full clinical examination, biochemical investigations including VLCFAs, liver and kidney function tests, neurophysiological examination including magnetic resonance image [MRI], electroencephalogram [EEG], auditory brain response [ABR] and visual evoked potential [VEP]. A neuropsychological evaluation was done to assess five psychological abilities [language, visual perception, memory, attention and psychomotor] and a global neuropsychological impairment score was developed. The subjects were subclassified into five groups according to the clinical and biochemical findings [neonatal ALD group [60%], adult ALD group [16%], adult Refsum's group [12%], Zellweger syndrome [87%] and rhizomelic chondrodysplasia punctata [4%]]. The main clinical, biochemical, neurophysiological and neuropsychological results were described among patients and control groups. In conclusion, the quantification of VLCFAs can be used as a highly reliable screening test for peroxisomal disorders, which also correlates with the severity of the disease and with the neurophysiological and neuropsychological impairment

Clinical and biochemical variability of the classical smith-lemli-opitz syndrome in Egyptians

Smith-Lemli-Opitz syndrome [SLO] is the first true metabolic malformation syndrome. The underlying defect is absent or deficient activity of 7-dehydrocholesterol reductase, which is the enzyme catalyzing the last step of cholesterol synthesis. We report on the first Egyptian cases [seven males] with SLO. We studied the clinical and biochemical variability of the syndrome and its relation to patients' age. Mental retardation, 2/3 toe syndactyly and genital anomalies were present in all patients. The distinct facial appearance became less obvious with age. All patients had marked elevation of plasma 7-dehydrocholesterol, which were measured by use of ultraviolet spectrometry. Plasma cholesterol measured by calorimetric method, were within the low normal range in most patients. Dietary cholesterol supplementation in two patients resulted in improvement of behaviour, better tolerance of infection, diminution of photosensitivity, pubertal progression and improvement in plasma sterol levels. The clinical phenotype of SLO is widely variable and plasma cholesterol levels are not reliable for detection of the syndrome. Therefore, diagnosis of SLO by demonstrating increased plasma concentrations of 7-dehydrocholesterol using ultraviolet spectrometry is a rapid and reliable method. Increased awareness of SLO is required for early diagnosis and dietary treatment of affected individuals