Role of plasma amino acids and urinary organic acids in diagnosis of mitochondrial diseases in children.

BACKGROUND: Diagnostic difficulty in mitochondrial diseases (MD) results not only from the wide spectrum of symptoms and signs but also from the absence of a reliable screening or diagnostic biomarker. AIM: To investigate the likelihood of MD in patients with symptoms and signs impressive of MD through quantitative measurement of plasma amino acids, and urinary organic acids. METHODS: Twenty patients with symptoms and signs suggestive of MD were further evaluated by quantitative plasma amino acids and urinary organic acids assay and neuroimaging. RESULTS: Plasma amino acid results revealed elevation of alanine in 11, glycine in five, and proline in two patients. Abnormal urinary organic acid analysis was present in six patients; increased urinary lactate (20%), dicarboxylicaciduria (15%), and urinary ketone bodies (10%). Upon enrollment our patients scored as possible MD according to the MD scoring system. At the end of the study, five patients still scored as possible MD, eight patients as probable MD, and seven patients as definite MD. All patients with definite MD had elevated serum lactate. In three patients, elevated urinary lactate was the only abnormality. Alanine was elevated in all patients with definite MD, whereas proline was elevated in only one. Magnetic resonance imaging of the brain showed atrophic changes in one patient and bilateral basal ganglia hyperintensity in another. CONCLUSION: Urinary organic acids and quantitative plasma amino acids can help in the diagnosis of MD, especially when the economic burden and absence of specialized centers limits the diagnosis.

Inherited thrombophilia in pediatric ischemic stroke: an Egyptian study.

Pediatric stroke is relatively uncommon, with often subtle clinical presentations. Numerous predisposing risk factors can be both inherited and acquired, including cardiac disease, vascular abnormalities, infectious diseases, collagen tissue diseases, inborn errors of metabolism, anticardiolipin antibody, lupus anticoagulant, deficiencies of protein C, protein S, antithrombin, or plasminogen, and prothrombotic mutations. We explored risk factors, clinical features, and neuroimaging among Egyptian children with ischemic stroke, and estimated the prevalence of inherited thrombophilia. We included 20 children with ischemic stroke, recruited from the Pediatric Neurology Outpatient Clinic (Ain Shams University). Basic clinical evaluations for stroke and genotyping for factor V 1691 G-A (factor V Leiden), prothrombin 20210 G-A mutations, and methylenetetrahydrofolate reductase 677 C-T polymorphisms were performed using real-time polymerase chain reaction, with fluorescent melting curve detection analysis. Ten patients (50%) manifested methylenetetrahydrofolate reductase polymorphisms (six homozygotes and four heterozygotes). Heterozygous factor V Leiden was present in five (25%), whereas prothrombin mutation was present in only one (5%). Five patients (25%) manifested combined prothrombotic abnormalities. Thirteen demonstrated evidence of inherited thrombophilic disorder; 25% manifested more than one mutation. For appropriate risk assessment, even in the presence of overt acquired thrombotic risk factors, physicians should request complete thrombophilia screening for patients with stroke.

Growth hormone levels in children and adolescents with epilepsy.

BACKGROUND: Patients with epilepsy often complain of symptoms that may be caused by disturbances in their hormonal balance. Disturbances in physical growth has been previously described. The aim of this study was to evaluate the effect of epilepsy and/or anti-epileptic drugs on the physical growth of patients with idiopathic epilepsy, as well as on the growth hormone (GH) and insulin growth factor-1 (IGF-1) status in those patients. METHODS: The study comprised 40 children and adolescents with idiopathic epilepsy on either valproate or carbamazepine. Anthropometric measurements [occipitofrontal circumference, weight, height, body mass index, span, and midarm circumference] were taken. Serum levels of GH before and after provocation with L-dopa and of IGF-1 were assessed. Results were compared to a matched control group. RESULTS: The height measurements were reduced in patients with epilepsy compared to the controls group. Though weight values were not significantly different, the body mass indices of the patients were significantly higher than controls, especially in patients on valproate therapy. Basal GH levels showed no significantly variation between patients and controls. However, post provocation GH and IGF-1 levels were significantly lower in patients. The type of epilepsy, disease duration, and the degree of seizure control had no significant effect on the studied parameters. In conclusion, physical growth seems to be affected in patients with epilepsy. This may be due to hormonal imbalance as evident by reduced post provocation GH levels and IGF-1 levels in the included group of patients.

Melatonin and sleep-related problems in children with intractable epilepsy.

Children with epilepsy have high rates of sleep problems. Melatonin has been advocated in treatment of sleep disorders, and its beneficial effect has been confirmed in insomnia. The aim of this study was to assess melatonin levels in children with intractable epilepsy and its relation to pattern of sleep and characteristics of seizure disorder, as well as the effect of melatonin therapy on those parameters. The study was conducted on 23 children with intractable epilepsy and 14 children with controlled seizures. Patients were evaluated by psychometric sleep assessment and assay of diurnal and nocturnal melatonin levels. Children with intractable epilepsy received oral melatonin before bedtime. They were reassessed after 3 months. Children with intractable epilepsy had higher scores for each category of sleep walking, forcible teeth grinding, and sleep apnea. At the end of therapeutic trial, patients with intractable epilepsy exhibited significant improvement in bedtime resistance, sleep duration, sleep latency, frequent nocturnal arousals, sleep walking, excessive daytime sleepiness, nocturnal enuresis, forcible teeth grinding, sleep apnea, and Epworth sleepiness scores. There was also significant reduction in seizure severity. Thus, use of melatonin in patients with intractable seizures was associated with improvement of both many sleep-related phenomena and the severity of seizures.

Anthropometry and body composition analysis in children with cerebral palsy.

BACKGROUND & AIMS: This study was undertaken to describe anthropometry, body composition parameters and assess serum levels of leptin and other biochemical markers of the nutritional status in a sample of Egyptian children with cerebral palsy(CP). METHODS: Anthropometric measurements (body weight, knee height, head, mid-upper arm, waist and hip circumferences, triceps and subscapular skin-fold thickness) were taken. Using the bioelectrical impedance technique, total body water(TBW), fat-free mass, fat mass, fat percentage and basal metabolic rate(BMR) were calculated. Serum levels of total proteins, albumin, ferritin and leptin were measured. Results were compared to that of healthy controls. RESULTS: Patients had significantly lower anthropometric measurements than controls, except for mid-upper arm and hip circumferences, and subscapular skin-fold thickness which were not different in both groups. Fat mass, fat free mass, fat percentage, TBW and BMR were lower in the patients. Serum protein and leptin levels were not different in patients and controls, though other biochemical markers were reduced in the patients. Patients with more severe motor handicap had lower skin-fold thickness, fat percentage and serum ferritin than those with milder affection. CONCLUSION: Parameters of growth, body composition analysis and nutritional status are significantly altered in CP patients especially those with severe motor handicap and oromotor dysfunction.

Autoantibody to heterogeneous nuclear ribonucleoprotein-A2 (RA33) in juvenile idiopathic arthritis: clinical significance.

BACKGROUND: Objective biomarkers are needed for early diagnosis of juvenile idiopathic arthritis (JIA). Anti-A33 antibodies are considered good markers for adult rheumatoid arthritis (RA), but little information is available on their occurrence in JIA. The aim of the present study was therefore to investigate the value of anti-RA33 for diagnosis of JIA (both early and established disease), and its relation to markers of disease activity, and bone resorption. SUBJECTS: This case-control study was conducted on 34 children with JIA. Ten patients with arthritis of short duration (<6 weeks) were included, as undifferentiated arthritis. Forty-four age- and sex- matched healthy children served as controls. Beside evaluation and assessment of disease activity, urinary calcium, serum parathyroid hormone and serum anti-RA33 were measured in included subjects. Joints were examined radiologically and modified Larsen index (LI) was estimated. RESULTS: During follow up, eight of the patients with undifferentiated arthritis were diagnosed as having early JIA. Patients with JIA (early and established cases) had higher anti-RA33 levels than the control group (z = 6.04, 3.95, respectively). A total of 66.7% of the patients were positive for anti-RA33, results were comparable in early and established cases. Anti-RA33 values were correlated to disease activity (clinical and laboratory), to laboratory markers (urinary calcium, parathyroid hormone levels) and radiological evidence (LI) of bone resorption (r = 0.95, 0.63, 0.94, respectively). CONCLUSION: Anti-RA33 is detected in two-thirds of JIA patients and occurs with comparable frequency early in the disease. Its levels are correlated to disease activity and markers of bone resorption and it seems to convey diagnostic and prognostic insights for appropriate management.

Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy.

PURPOSE: We aimed to evaluate the effect of epilepsy on the reproductive hormones levels among female patients, and to investigate the frequency of catamenial pattern of seizures. METHODS: A total of 42 female patients with epilepsy and 21 healthy females (control group) were included. Subjects were at least 2 years postmenarche with regular cycles. Symptoms of premenstrual syndrome (PMS) were assessed using calendar of premenstrual experience scoring. Patients were evaluated for catamenial pattern of seizures. Levels of FSH, LH, estradiol (E), and progesterone (P) were assessed for all subjects in the three phases of the cycles. Pelvi-abdominal ultrasound was performed near time of ovulation, to follow up size of mature follicle. RESULTS: Symptoms of PMS were not different in patients and controls, or in patients with and those without catamenial tendency. In both perimenstrual (M) and midluteal phases, FSH and P levels were lower and E/P ratio higher in patients group. There was a catamenial pattern of seizures in 31% of patients (53.8% M C(1); 46.15% inadequate luteal phase C(3)pattern). Patients with C(3)pattern showed lower P levels in the midluteal phase compared to patients with noncatamenial pattern, to those with C(1)pattern or to controls. Patients with C(1)pattern had lower P levels than controls in the M phase. CONCLUSION: There was evident disruption in the reproductive hormones in female patients with epilepsy with lower FSH and P levels and higher E/P ratio. A total of 31% of patients showed catamenial pattern of seizures (C(1)and C(3)patterns) that was significantly related to P withdrawal.

Plasma interleukin-1beta levels in children with febrile seizures.

Proinflammatory and anti-inflammatory cytokines regulate the febrile response during infection. In this study, the role of cytokines in the pathogenesis of febrile seizures was investigated, through comparing levels of interleukin-1beta in the peripheral blood of children with febrile seizures and in a matched control group of children with febrile illnesses without seizures. The study included 33 children with febrile seizures (mean +/- SD, 29.94 +/- 14.9 months) and 38 controls with comparable age, sex, and type of infection. A laboratory workup for the diagnosis of infection was performed, and interleukin-1beta levels were assessed by enzyme-linked immunosorbent assay for the patients and the control groups immediately on arrival at the hospital. The plasma levels of interleukin-1beta were comparable in the patients and the control group (mean +/- SD, 7.321 +/- 3.123 and 8.087 +/- 4.8 pg/mL, respectively). Furthermore, there was no significant difference when comparing the plasma levels of interleukin-1beta in patients with simple and complex types of febrile seizures. Plasma interleukin-1beta levels did not show a significant correlation to either the duration of the last seizure, the number of the previous attacks of febrile convulsion, or the degree of temperature. However, interleukin-1beta levels were negatively correlated to the duration from the last seizure attack (r = -.8). Thus, the results of the present study do not support the hypothesis that increased production of interleukin-1beta is involved in the pathogenesis of febrile seizures in children.

Rectal bleeding in Egyptian children.

AIM: In a prospective study to outline the aetiology of bleeding per rectum (BPR) in Egyptian infants and children, a subsidiary aim was to define some of the clinical characteristics of the different aetiologies. SUBJECTS AND METHODS: 194 children with BPR are described. The diagnostic work-up included laboratory investigations, radiological and endoscopic assessment, radio-isotope scanning, angiography and histopathological examination of mucosal biopsies, as appropriate. RESULTS: Ages ranged from 3 to 192 months with a mean (SD) of 49.8 (43.5). Infectious enterocolitis was the most common cause (37.1%). Others included colorectal polyps (21.1%), chronic colitis (16%) including inflammatory bowel diseases (5.2%), allergic colitis (2.6%), solitary rectal ulcer syndrome (1.5%) and non-specific colitis (6.7%). Intussusception and Meckel's diverticulae were the cause in 7.3% and 2.6%, respectively, while other aetiologies included vascular (6.2%), systemic (3.6%), local anal (3.1%) and upper gastro-intestinal causes (1.5%). In 1.5% of cases, the cause remained 'obscure'. CONCLUSION: In Egyptian children, infectious enterocolitis followed by colorectal polyps and chronic colitis are major causes of BPR.

Physical growth and endocrinal disorders during pubertal maturation in girls with epilepsy.

PURPOSE: This study investigated the effect of epilepsy and/or antiepileptic drugs (AEDs) on the physical growth, pubertal development, and androgenic status of girls with epilepsy between ages 8 and 18 years. METHODS: Sixty-six female patients with epilepsy, their mean ages 13.47 +/- 3.5 years, were included. Anthropometric measurements, staging of pubertal maturation, and clinical manifestations of hyperandrogenism were assessed, as well as measurement of serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), and free androgen index (FAI). Of the included patients, 44 had transabdominal ultrasonic examination of the ovaries and fasting serum insulin levels were measured. Forty healthy age-matched females served as a control group. RESULTS: Patients showed reduced mean height percentile compared with controls (z = 2.07; p = 0.04), which was negatively correlated with the duration of their epilepsy. Patients showed increased frequency of obesity, especially postpubertal girls taking valproate (VPA; 67%), who also showed higher insulin levels (t = 8.01; p = 0.0003). Patients showed increased frequency of clinical hyperandrogenemia in the different stages of puberty. High levels of testosterone and DHEAS were found in female patients with epilepsy, especially pubertal and postpubertal girls. Hyperandrogenism (clinical and/or laboratory) was most affected by the types of AEDs, with higher incidence in patients taking VPA compared with those taking enzyme-inducing AEDs (chi2= 9.16; p = 0.01). Eighteen percent of the patients were diagnosed as having polycystic ovary syndrome (PCOS). No difference was found in the types of seizures, degree of seizure control, type of AEDs, or insulin levels between patients with and those without PCOS. CONCLUSIONS: Longer duration of the disease has a negative impact on the stature of female patients with epilepsy. Postpubertal girls taking VPA are more liable to obesity, which is associated with increased incidence of hyperinsulinemia. Clinical and/or laboratory evidence of hyperandrogenism is seen at a high frequency in patients, especially with the use of VPA. Furthermore, female patients with epilepsy especially in the postpubertal stage of sexual maturation, have a high prevalence of PCOS, independent of the type of AED or the characteristics of the epilepsy disorder.

Physical and hormonal profile of male sexual development in epilepsy.

PURPOSE: This study was designed to investigate the effect of epilepsy and antiepileptic drugs (AEDs) on both the physical and hormonal aspects of the sexual development of male patients with epilepsy. METHODS: One hundred thirty male subjects with epilepsy, their age ranging between 8 and 18 years (mean, 14 +/- 2.9 years), entered the study; all were taking AEDs. Anthropometric measurements [height, weight, and body mass index (BMI)], testicular volume, penile length, and pubarche were assessed in the studied groups, as well as measurement of the levels of testosterone (T), free testosterone (FT), estradiol (E2), lutenizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL), and the results were compared with those of a control group. RESULTS: In this study, male patients older than 16 years were significantly shorter than their matched controls. The mean values of testicular volume and penile length were significantly lower in the patients in the different age subgroups, and the pubic hair staging (pubarche) was delayed in the patients older than 16 years. The mean values of total testosterone, estradiol, LH, and FSH serum levels were significantly higher, whereas the mean values of free testosterone, total-T/E2, total. T/LH, and FT/E2 ratios were lower in the patient subgroups compared with their age-matched controls. There were no significant changes in the mean basal PRL serum levels in the patients compared with the controls. The present study demonstrated a reduction in the testicular volume and penile length, significantly lower mean values of free testosterone and total-T/E2, and a higher mean value of E2 in the patients receiving polytherapy in the age subgroup older than 16 years compared with those on monotherapy; however, there was no demonstrable effect of seizure control or the duration of illness in any of the studied parameters. CONCLUSIONS: There is a delay in the sexual development of male patients with epilepsy in the different age subgroups, with endocrine changes in the form of increase in the total testosterone, but the free testosterone is lower, and an increase in estradiol, with lower T/LH levels. Patients receiving polytherapy, especially those older than 16 years, were more likely to have delayed gonadarch and disturbances in their hormonal profile.