Neuroimaging findings in infantile GM1 gangliosidosis

GM1 gangliosidosis is an autosomal recessive glycosphingolipid storage disease caused by defects in the enzyme beta-galactosidase. Three clinical forms (infantile-, juvenile-, and adult-onset) of the disease are recognized. Patients with infantile GM1 gangliosidosis present at birth or shortly thereafter with somatic and bony changes, followed by severe neurological deterioration ultimately leading to death within the first 2 years of life. We present the brain CT, MRI and MR spectroscopy (MRS) findings in a 17-month-old Turkish girl with infantile GM1 gangliosidosis. Neuroimaging findings in patients with infantile GM1 gangliosidosis have been reported only in a few cases. In this study, MRS of the thalamus was performed to study the metabolic changes in GM1 gangliosidosis. We showed a a decreased NAA/Cr ration and an increased Cho/Cr ratio. To our knowledge, this is the first report of magnetic resonance spectroscopy findings in type-1 GM1 gangliosidosis.     

Increased levels of soluble adhesion molecules E-selectin and P-selectin in patients with cardiac syndrome X

The role of endothelial dysfunction and platelet activation in patients with cardiac syndrome X is controversial. The aim of this study was to investigate the plasma levels of circulating E- and P-selectin molecules in patients with syndrome X. The study included 21 patients with cardiac syndrome X (11 men and 10 women, mean age = 56 +/- 5 years) and 20 patients with significant coronary artery disease who had stable angina pectoris (11 men and 9 women, mean age = 60 +/- 8 years). Twenty-two age- and sex-matched subjects (12 men and 10 women, mean age = 58 +/- 8 years) undergoing diagnosis of atypical chest pain in whom coronary arteries were found normal and exercise test had no signs of ischemia served as the control group. Syndrome X was defined as presence of typical chest pain on exertion or at rest with positive exercise test and angiographically normal epicardial coronary arteries with no evidence of coronary spasm after intracoronary infusion of ergonovine maleate. The mean plasma concentrations of P-selectin were significantly elevated both in patients with coronary artery disease and syndrome X as compared with control subjects (49.15 +/-7.47 and 42.80 +/- 8.93 vs 22.63 +/-6.47 ng/mL, p < 0.001). Similarly, both patients with coronary artery disease and syndrome X had higher plasma concentrations of E-selectin than the control group (78.85 +/- 16.69 and 68.38 +/- 15.30 vs 36.43 +/- 4.72 ng/mL, p < 0.001). In conclusion, patients with syndrome X had increased plasma concentrations of soluble adhesion molecules, E-selectin and P-selectin, reflecting an ongoing chronic inflammation involved with endothelial dysfunction and enhanced platelet activation/damage in this setting.     

Ceruloplasmin levels in antineutrophil cytoplasmic antibody-positive patients

Anti-myeloperoxidase (MPO) antibodies are associated with the development of anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. The imbalance between the protease-antiprotease activity in the neutrophils has been implicated in the pathogenesis of ANCA-related vasculitis. Ceruloplasmin is an acute-phase protein that has antiproteinase and antioxidant properties and inhibits MPO activity. We attempted to study the association between serum ceruloplasmin and ANCA in childhood vasculitis. Forty-five ANCA-related diseases were included in the study. The age range was 4-16 years. Patients were divided into two groups based on indirect immunofluorescence and/or ELISA specificity (MPO). Twenty-six patients had p-ANCA- and 19 patients had c-ANCA-positive disease. Nine patients with Henoch-Sch?nlein purpura were studied as an ANCA-negative control group. Serum ceruloplasmin levels in p-ANCA-, c-ANCA-positive patients, and controls were 125.85+/-93.48 mg/dl, 59.79+/-17.60 mg/dl, and 64.34+/-18.77 mg/dl, respectively, and were significantly higher in patients with p-ANCA ( P<0.05). Ceruloplasmin levels were significantly decreased in remission ( P<0.05). Median MPO level in p-ANCA-positive patients was 15.2 (5-250) and was negative in all c-ANCA-positive patients. There was a significant positive correlation between MPO and ceruloplasmin levels ( r=0.70, P<0.05). Of 26 patients (53.8%) in the p-ANCA-positive group, 14 had renal involvement. The patients with renal disease had significantly higher ceruloplasmin levels than others (151.17+/-92.14 and 134.64+/-95.16 mg/dl respectively, P<0.05). In conclusion, the increase in ceruloplasmin levels during the acute phase suggests that this might be an activation criterion or a response to neutrophil-mediated tissue injury. Increased ceruloplasmin levels together with p-ANCA positivity may be predictive for renal involvement and a serious clinical course. The correlation between ceruloplasmin and MPO levels supports their association. Further studies are necessary to elucidate whether genetic and/or functional alterations in ceruloplasmin are effective in the pathogenesis of vasculitis.     

Prolidase deficiency

A 32‐year‐old mentally retarded woman was admitted to hospital with recurrent ulcers on her legs, which appeared for the first time at 8 years of age. Apart from recurrent lower respiratory tract infections and chronic otitis media, her personal history was unremarkable. Her parents were second‐degree relatives. The family history showed no similar disease or mental retardation. Physical examination revealed that the patient had an unusual facial appearance, with a high‐arched palate; she had multiple tooth caries ( Fig. 1 ).

Figure Figure 1  Open in figure viewer PowerPoint Facial appearance of the patient     

Most reliable indices in differentiation between thalassemia trait and iron deficiency anemia

BACKGROUND: Iron deficiency anemia (IDA) and thalassemia trait (TT) are the most common forms of microcytic anemia. Some discrimination indices calculated from red blood cell indices are defined and used for rapid discrimination between TT and IDA. However, there has been no study carried out in which the validity of all of the defined indices are compared in the same patient groups. Youden's index is the most reliable method by which to measure the validity of a particular technique, because it takes into account both sensitivity and specificity. METHODS: We calculated eight discrimination indices (Mentzer Index, England and Fraser Index, Srivastava Index, Green and King Index, Shine and Lal Index, red blood cell (RBC) count, red blood cell distribution width and red blood cell blood distribution width index (RDWI)) in 26 patients with IDA and in 37 patients with beta TT (betaTT). We determined the number of correctly identified patients by using each discrimination index. We also calculated sensitivity, specificity, positive and negative predictive value and Youden's index of each discrimination index. RESULTS: None of the discrimination indices showed a sensitivity and specificity of 100%. Youden's indices of RBC count and RDWI were the highest with the value of 82 and 80%, respectively. Ninety percent and 92% of the patients were correctly identified with RBC and RDWI, respectively. CONCLUSIONS: Red blood cell count and RDWI are the most reliable discrimination indices in differentiation between betaTT and IDA.     

Scintigraphic findings in osteoarticular brucellosis

AIMS: To describe the distribution of bone and joint involvement in 197 patients with brucellosis, and to detail a spectrum of findings on bone scintigraphy in 38 patients with brucellar spondylitis. METHODS: One hundred and ninety-seven patients (141 females, 56 males; age range, 5-77 years) with osteoarticular brucellosis were studied. Patients were classified into acute (62%) and chronic (38%) stages of the disease, and into age groups of less than 16 (1%), 16-30 (17%), 31-45 (29%), 46-60 (37%) and over 60 (16%) years. All patients were evaluated with Tc-methylene diphosphonate bone scanning. Quantification of sacroiliac joint uptake was performed to improve the sensitivity for the detection of sacroiliitis. Plain radiography and computed tomography (CT) or magnetic resonance imaging (MRI) were performed, when required, to evaluate the areas of the skeleton that showed abnormal uptake on the bone scan. MRI and single photon emission computed tomography (SPECT) were performed in all patients who had spinal lesions. RESULTS: The sites most commonly affected were the sacroiliac joints (53%) and spine (19%), followed by the shoulders (16%). Osteoarticular involvement was more common in females (72%) than in males (28%), and the acute stage (62%) was observed more than the chronic stage (38%). Bone and joint involvement occurred at any age, but the most common age group was 46-60 years. Eight scintigraphic patterns were identified in spinal involvement. CONCLUSION: Brucellosis may affect the musculoskeletal system at any site. Bone scan is a useful method to detect osteoarticular involvement in cases of relapse and progression. Spine involvement has the widest range of scintigraphic findings. A knowledge of the location and distribution of osteoarticular involvement as revealed on the bone scan of patients with brucellosis may be valuable in patient treatment and management.     

Juvenile polyarteritis: results of a multicenter survey of 110 children

OBJECTIVE: To characterize pediatric patients who had been diagnosed with polyarteritis nodosa (PAN) through necrotizing vasculitis of the small and mid-size arteries or those with characteristic findings on angiograms data were collected. STUDY DESIGN: Pediatricians were asked to classify their patients into one of the four suggested groups for juvenile PAN. Twenty-one pediatric centers worldwide participated with 110 patients. RESULTS: The girl:boy ratio was 56:54, with a mean age of 9.05 +/- 3.57 years. The cases were classified as: 33 (30%) cutaneous PAN; 5 (4.6%) classic PAN associated with hepatitis B surface antigen (HBs Ag); 9 (8.1%) microscopic polyarteritis of adults associated with antineutrophil cytoplasmic antibodies (ANCA); and 63 (57.2%) systemic PAN. Cutaneous PAN was disease confined to the skin and musculoskeletal system. All patients with HBs Ag-associated classic PAN were diagnosed with renal angiograms. Antiviral treatment was administered in most cases. Microscopic PAN patients had pulmonary-renal disease, in combination or separately. ANCA was present in 87%, and 2 patients progressed to end-stage renal failure. Patients classified with systemic PAN had multiple system involvement, almost all had constitutional symptoms, and all had elevated acute phase reactants. Corticosteroids and cyclophosphamide were the first choices of immunosuppressive treatment. The overall mortality was 1.1%. CONCLUSIONS: There were remarkable differences among pediatric patients with PAN, with different clinical manifestations and overall better survival and lower relapse rates when compared with adults.     

Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome

BACKGROUND: Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant nephrotic syndrome (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes for end-stage renal disease (ESRD) in the first two decades of life. Sporadic mutations in the Wilms' tumor suppressor gene WT1 have been found to be present in patients with SRNS in association with Wilms' tumor (WT) and urinary or genital malformations, as well as in patients with isolated SRNS. METHODS: To further evaluate the incidence of WT1 mutations in patients with NS we performed mutational analysis in 115 sporadic cases of SRNS and in 110 sporadic cases of steroid-sensitive nephrotic syndrome (SSNS) as a control group. Sixty out of 115 (52%) patients with sporadic SRNS were male, 55/115 (48%) were female. Sex genotype was verified by haplotype analysis. Mutational analysis was performed by direct sequencing and by denaturing high-performance liquid chromatography (DHPLC). RESULTS: Mutations in WT1 were found in 3/60 (5%) male (sex genotype) cases and 5/55 (9%) female (sex genotype) cases of sporadic SRNS, and 0/110 (0%) sporadic cases of SSNS. One out of five female patients with mutations in WT1 developed a WT, 2/3 male patients presented with the association of urinary and genital malformations, 1/3 male patients presented with sexual reversal (female phenotype) and bilateral gonadoblastoma, and 4/5 female patients presented with isolated SRNS. CONCLUSION: According to the data acquired in this study, patients presenting with a female phenotype and SRNS and male patients presenting with genital abnormalities should especially be screened to take advantage of the important genetic information on potential Wilms' tumor risk and differential therapy. This will also help to provide more data on the phenotype/genotype correlation in this patient population.     

Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome

Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant NS (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes of ESRD in the first two decades of life. Mutations in the NPHS2 gene represent a frequent cause of SRNS, occurring in approximately 20 to 30% of sporadic cases of SRNS. On the basis of a very small number of patients, it was suspected that children with homozygous or compound heterozygous mutations in NPHS2 might exhibit primary steroid resistance and a decreased risk of FSGS recurrence after kidney transplantation. To test this hypothesis, NPHS2 mutational analysis was performed with direct sequencing for 190 patients with SRNS from 165 different families and, as a control sample, 124 patients with steroid-sensitive NS from 120 families. Homozygous or compound heterozygous mutations in NPHS2 were detected for 43 of 165 SRNS families (26%). Conversely, no homozygous or compound heterozygous mutations in NPHS2 were observed for the 120 steroid-sensitive NS families. Recurrence of FSGS in a renal transplant was noted for seven of 20 patients with SRNS (35%) without NPHS2 mutations, whereas it occurred for only two of 24 patients with SRNS (8%) with homozygous or compound heterozygous mutations in NPHS2. None of 29 patients with homozygous or compound heterozygous mutations in NPHS2 who were treated with cyclosporine A or cyclophosphamide demonstrated complete remission of NS. It was concluded that patients with SRNS with homozygous or compound heterozygous mutations in NPHS2 do not respond to standard steroid treatment and have a reduced risk for recurrence of FSGS in a renal transplant. Because these findings might affect the treatment plan for childhood SRNS, it might be advisable to perform mutational analysis of NPHS2, if the patient consents, in parallel with the start of the first course of standard steroid therapy.