Hypothyroidism could be the only manifestation of mitochondrial T8993C mutation in Leigh syndrome

Mitochondrial DNA-associated Leigh syndrome is a part of a continuum of progressive neurodegenerative disorders caused by abnormalities of mitochondrial energy generation. Mitochondrial T8993C and T8993G mutations account for 10-20% of these cases. T8993C is generally associated with milder phenotype than T8993G mutation. Here we report an Egyptian family with T8993C mutation with unusual early onset of severe phenotype in three sisters [consisting of regression of previously acquired motor and mental milestones after an attack of viral infection] and hypothyroidism as the only presenting symptom in their brother. The mother [like her son] carried the T8993C mutation and was asymptomatic. This unusual lack of manifestation could be attributed to different percentages of mutated mitochondrial DNA in the brain or muscle or perhaps to some unknown protective factor. The hypothyroidism could be a simple association, but to the best of our knowledge, no previous reports have described hypothyroidism in carriers of this mutation

Hepatocerebral form of mitochondrial DNA depletion syndrome due to mutation in MPV17 gene

Mitochondrial DNA depletion syndromes [MDSs] are autosomal recessive diseases characterized by a severe decrease in mitochondrial DNA content leading to dysfunction of the affected organ. Autosomal recessive mutations in MPV17 have been identified in the hepatocerebral form of MDS. We describe the clinical features, biochemical and molecular results of a Saudi infant with a new mutation of MPV17 and compared the features to those of previously reported cases. We stress the importance of such rare cases particularly in countries with high consanguineous marriage rate

High plasma levels of adrenomedullin in collagen diseases

Background: Adrenomedullin [ADM], a potent vasorelaxant/hypotensive peptide, was shown recently to be over-expressed in inflammatory rheumatic diseasesaaaaa

Objectives: The aim of this study was to investigate the value of ADM as a laboratory marker of disease activity in juvenile rheumatoid arthritis [JRA] and pediatric onset- systemic lupus erythematosus [SLE] and its relation to other markers of disease activity such as clinical scores, the ESR and tumor necrosis factor-alpha [TNF- alpha]

Methods: The study included 24 patients with JRA, 17 with childhood onset- SLE, as well as, 19 with rheumatic arthritis and twenty clinically healthy age- and sex- matched subjects. Clinical evaluation for disease activity was performed using the clinical activity score index in JRA, and SLE-DAI in SLE. Subjects were investigated to verify the diagnosis and disease activity. Plasma ADM and serum of TNF- alpha levels were then assayed

Results: Serum TNF- alpha and plasma ADM levels were significantly higher in JRA and SLE patients than in rheumatic arthritis patients and healthy controls. Though serum TNF- alpha and plasma ADM levels were both higher in JRA [73.88+11.6 pg/ml and 156.5+22.4 pg/ml, respectively] compared to SLE [48.82+7.5 pg/ml and 85.12+15.7 pg/ml, respectively], the difference was of statistical significance only in ADM. Both serum TNF- alpha and plasma ADM levels were significantly higher in systemic onset-JRA [139.75+18.5 and 260.25+28.6 pg/ml, respectively] compared to the pauciarticular-onset type [33.8+3.04 and 93.4+9.35 pg/ml, respectively], but comparable to the polyarticular onset cases [69.97+8.45 and 149.87+21.15 pg/ml, respectively]. Positive correlations were noticed between plasma ADM and activity score index [r=0.72], ESR [r=0.59] and serum TNF-alpha [r=0.64] in JRA. The serum TNF- alpha was not influenced by the site of lupus activity unlike plasma ADM that was higher in subjects suffering from lupus arthritis or cardiovascular manifestations. The afore-mentioned markers correlated positively to the ESR in SLE but not to the SLE-DAI. With a cut-off value of TNF-alpha = 31 pg/ml and that for ADM = 80 pg/ml calculated from the results of the included rheumatic arthritis patients, ADM appeared to be a more sensitive marker of activity in JRA and SLE compared to TNF- alpha

Conclusion: Plasma ADM was over-expressed in JRA and SLE. It correlated with the clinical and biochemical activity markers in JRA suggesting that it can be used as an indicator of disease activity. In SLE, ADM levels correlated with ESR and TNF- alpha levels and it could be of value in identifying patients with arthritis and cardiac involvement

Osteoprotegerin in juvenile rheumatoid arthritis: cross talk between the immune and the skeletal systems

Background: Previous studies have linked the decreased local production of osteoprotegerin [OPG], an osteoclastogenesis blocking agent, in the inflamed joints of rheumatoid arthritis patients to the development of bone erosion

Objective: We sought to assess OPG expression in juvenile rheumatoid arthritis [JRA] and to determine its relation to clinical and laboratory markers of disease activity, and radiologic evidence of bone resorption, as well as its relation to the type of onset, duration of illness and different therapeutic modalities

Methods: The study included 40 children and adolescents with JRA, as well as, 20 clinically healthy age- and sex- matched subjects for comparison. The patients underwent clinical evaluation for disease activity by the summed joint index and investigations including assessment of ESR, CRP, antinuclear antibodies and rheumatoid factor were Serum levels of osteoprotegerin were assayed by ELISA in the patient and control groups. Joints were evaluated radiologically using the modified Larsen index [LI]

Results: The serum levels of OPG in the patients [median [interquartile range]: 0.474 [0.4] ng/ml] were comparable to those of the control group [0.495 [0.41] ng/ml] [p=0.29]. However, patients with pauciarticular onset JRA had significantly lower OPG levels [0.3 [0.23] ng/ml] than the control group [p= 0.007]. The OPG levels were below the 5th percentile of the control value in 60% of pauciarticular and 16.7% of polyarticular JRA cases. Patients with polyarticular JRA had significantly higher values of ESR, activity score and Larsen indices as well as serum OPG levels [p= 0.001, 0.001, 0.002 and 0.02, respectively]. OPG levels did not correlate to the ESR or the activity score index values. On the other hand, the duration of illness showed a tendency to be negatively correlated to serum OPG [r=-0.309, p=0.05]. LI correlated positively to the activity score index and to the ESR in the JRA patients, whether compiled in one group or classified into subgroups according to disease onset. However, OPG was not significantly correlated to the LI [r= 0.023]. The different modalities of therapy did not seem to influence the serum levels of OPG [X2 = 4.21]

Conclusion: Serum OPG expression was low in JRA, especially in the pauciarticular variety. OPG levels were higher in polyarticular JRA, but this does not necessarily have a protective effect since the proinflammatory process is known to promote also the expression of RANKL, an osteoclastogenesis enhancer. While clinical and biochemical parameters of activity, and LI did not correlate to OPG, the latter seemed to be adversely affected by increased disease duration

Antiphospholipid antibodies in children and adolescents with epilepsy

Background: Some immunologic mechanisms of epilepsy are cited in literature. The possibility that epilepsy might be associated with the production of autoantibodies has not been sufficiently addressed

Objective: This study investigates the prevalence of some antiphospholipid antibodies in pediatric primary epilepsy in relation to the type of seizures, the duration of the disease and the antiepileptic drugs received

Methods: The study included 37 patients in the pediatric age groups with epilepsy [30 with idiopathic epilepsy and 7 with cryptogenic epilepsy]; 10 of them were newly diagnosed in comparison to ten healthy children. The patients were subjected to clinical, laboratory and radiologic evaluation to verify the diagnosis and to exclude thrombotic or autoimmune collagen disorders. Anticardiolipin IgG and IgM and anti-beta2-glycoprotein I IgG and IgM antibodies were measured in all subjects using the ELISA technique

Results: Forty percent of the patients were positive for at least one of the antiphospholipid antibodies and 16% displayed more than one antibody in their serum. The mean values of anti CL IgG and anti beta2GP I IgM were significantly higher in the patients [mean 11.32 +/- 6.3 GPL and 4.43 +/- 2.8 U/ml, respectively] as compared to the control group [mean 5.25 +/- 1.9 and 1.6 +/- 0.6, respectively] [P<0.001]. The concentrations of the tested antibodies were comparable among patients with focal compared to those with generalized seizure, or in patients with idiopathic compared to cryptogenic epilepsy. Patients with newly diagnosed untreated epileptic seizures showed a substantial prevalence of antiphospholipid antibodies. They even demonstrated significantly higher mean values of a beta2GP I IgG [10.7 +/- 11 GPL] and a?2GP I IgM [5.8 +/- 3.0 U/ml] when compared to the rest of the patients [mean 5.9 +/- 3.5 and 3.9 +/- 2.6 respectively].There seem to be no effect of the different antiepileptic drugs or the degree of seizure control on the development of antiphospholipid antibodies

Conclusions: The antiphospholipid antibodies seem to be present at a higher rate in pediatric patients with epilepsy. The increased prevalence of those autoantibodies is associated with epilepsy regardless of the type of seizures, the antiepileptic drugs used or the degree of seizure control, suggesting that immune dysregulation may be linked to the pathogenesis of primary epilepsy