Diffuse and multifocal nephrogenic adenoma with Familial Mediterranean Fever: a case report with molecular study.

Nephrogenic adenoma, also referred to nephrogenic metaplasia, is a benign proliferative lesion of urothelium, usually associated with chronic physical stimuli or inflammation. Familial Mediterranean fever is an inherited autosomal recessive disease characterized by recurrent short episodes of fever. The site of mutation is found in MEFV gene which controls inflammatory responses. We have experienced a case of nephrogenic adenoma in a 16-year-old girl with Familial Mediterranean Fever, showing proliferative lesions diffusely in the urinary bladder and multifocally in the other parts of urinary tract. These lesions disappeared after colchicine treatment. We searched for MEFV gene mutation using the specimen from the resected urinary bladder and detected heterozygous mutation of E148Q. There is a possibility that control of inflammation caused by the surgery for vesicoureteral reflux in the local site didn't work well on the background of heterozygous mutation of MEFV gene, and as a result, nephrogenic adenoma appeared. This is the first report of a combination of two rare diseases. We have to be aware that nephrogenic adenoma can occur in association with Familial Mediterranean Fever, and the former condition should be taken into consideration when rendering a correct pathological diagnosis.

Disappearance of frontal N30 component of median nerve stimulated SSEPs in two young children with abnormal striatal lesions.

Median nerve stimulated short-latency somatosensory evoked potentials (MN-SSEPs) were performed in two young children with extrapyramidal symptoms. Brain MRI showed bilaterally symmetric striatal lesions in both cases. The subcortical components (N9, N11, N13, N18, P11, and P13) and the parietal component (N20) were normally detected, whereas the frontal component (N30) was not detected bilaterally in either case. In conclusion, our findings suggest that frontal N30 disappearance could be observed since as early as young childhood and it may pathophysiologically reflect severe dysfunction in the extrapyramidal system.

A case of juvenile myelomonocytic leukemia with concomitant cytomegalovirus infection.

Infantile cytomegalovirus (CMV)-associated disease and juvenile myelomonocytic leukemia (JMML) frequently present with similar clinical features, and thus the differential diagnosis is often difficult. An early and definite diagnosis of these disorders is required because their therapeutic approaches are very different. The authors describe a 2-month-old Japanese girl with JMML and CMV infection. The CMV antigen was detected by immunologic staining of leukocytes using the peroxidase-labeled monoclonal antibody HRP-C7. To assess clonality, the X-chromosome inactivation pattern was evaluated using polymerase chain reaction analysis of the human androgen receptor gene with or without predigestion of chromosomal DNA with HhaI or HpaII. The patient showed evidence of monoclonal origin of mononuclear cells at diagnosis. Although CMV infection mimicking JMML has previously been reported in two patients, to the authors' knowledge this is the first report describing a firm and definitive diagnosis of JMML based on the study of X-chromosome inactivation patterns.

The molecular basis of glycogen storage disease type 1a: structure and function analysis of mutations in glucose-6-phosphatase.

Glycogen storage disease type 1a is caused by a deficiency in glucose-6-phosphatase (G6Pase), a nine-helical endoplasmic reticulum transmembrane protein required for maintenance of glucose homeostasis. To date, 75 G6Pase mutations have been identified, including 48 mutations resulting in single-amino acid substitutions. However, only 19 missense mutations have been functionally characterized. Here, we report the results of structure and function studies of the 48 missense mutations and the DeltaF327 codon deletion mutation, grouped as active site, helical, and nonhelical mutations. The 5 active site mutations and 22 of the 31 helical mutations completely abolished G6Pase activity, but only 5 of the 13 nonhelical mutants were devoid of activity. Whereas the active site and nonhelical mutants supported the synthesis of G6Pase protein in a manner similar to that of the wild-type enzyme, immunoblot analysis showed that the majority (64.5%) of helical mutations destabilized G6Pase. Furthermore, we show that degradation of both wild-type and mutant G6Pase is inhibited by lactacystin, a potent proteasome inhibitor. Taken together, we have generated a data base of residual G6Pase activity retained by G6Pase mutants, established the critical roles of transmembrane helices in the stability and activity of this phosphatase, and shown that G6Pase is a substrate for proteasome-mediated degradation.