Nephrotic Syndrome in a Child With NPHS2 Mutation.

Steroid resistant nephrotic syndrome (SRNS) accounts for 30% of all cases of nephrotic syndrome (NS) in children and frequently leads to end stage kidney disease (ESKD). About 30% of children with SRNS demonstrate causative mutations in podocyte- associated genes. Early identification of genetic forms of SRNS is critical to avoid potentially harmful immunosuppressive therapy. A 2-year-old male patient with NS and no family history of renal disease did not respond to 4-week steroid treatment. Kidney biopsy demonstrated mesangial proliferative glomerulopathy with basement membrane dysmorphism. Tacrolimus and Lisinopril were added to therapy pending results of genetic testing. Kidney Gene panel showed a NPHS2 c.413G>A (p.Arg138Gln) homozygous pathogenic variant. This missense variant is considered a common pathogenic founder mutation in European populations. A diagnosis of autosomal-recessive form of nonsyndromic SRNS due to NPHS2 causative variant was made. Immunosuppresive therapy was stopped, Lizinopril dose was increased and weekly infusions of Albumin/furosemide were initiated to manage edema. This case demonstrates that early genetic testing in children with SRNS avoids prolonged potentially harmful immunosuppressive therapy, allows for timely genetic family counseling, and allows earlier consideration for future living related donor kidney transplantation.

Current Utilization of Electron Microscopy in the Pediatric Pathology Setting: A Survey by the SPP Practice Committee.

BACKGROUND: Electron microscopy (EM), once an important component in diagnosing pediatric diseases, has experienced a decline in its use. To assess the impact of this, pediatric pathology practices were surveyed regarding EM services. METHODS: The Society of Pediatric Pathology Practice Committee surveyed 113 society members from 74 hospitals. Settings included 36 academic tertiary, 32 free-standing children's, and 6 community hospitals. RESULTS: Over 60% maintained in-house EM services and had more than 2 pathologists interpreting EM while reporting a shortage of EM technologists. Freestanding children's hospitals had the most specimens (100-200 per year) and more diverse specimen types. Hospitals with fewer than 50 yearly specimens often used reference laboratories. Seventeen had terminated all in-house EM services. Challenges included decreasing caseloads due to alternative diagnostic methods, high operating costs, and shortages of EM technologists and EM-proficient pathologists. Kidney, liver, cilia, heart, and muscle biopsies most often required EM. Lung/bronchoalveolar lavage, tumor, skin, gastrointestinal, nerve, platelet, and autopsy samples less commonly needed EM. CONCLUSIONS: The survey revealed challenges in maintaining EM services but demonstrated its sustained value in pediatric pathology. Pediatric pathologists may need to address the centralization of services and training to preserve EM diagnostic proficiency among pathologists who perform ultrastructural interpretations.

Early identification of transplant glomerulopathy in pediatric kidney transplant biopsies: A single-center experience with electron microscopy analysis.

Banff 2013 criteria recommend performing ultrastructural studies with electron microscopy (EM) in kidney transplant biopsies if the technology is available. We sought to determine the impact of EM on enhancing diagnostic findings in pediatric kidney transplant biopsies and the prognostic information gained from the additional findings. All kidney transplant biopsies since routine EM use started on June 1, 2014, until October 31, 2016, were reviewed. Primary outcome measures included the positive yield frequency of EM use defined as an upgraded diagnosis based on EM findings relative to light microscopy, and 12-month kidney allograft outcome of progression to ESRD or doubling of serum creatinine stratified by transplant glomerulopathy (TG) status on EM. Eighty unique kidney transplant biopsies were reviewed. EM studies were completed for 61 biopsies (76%). Complication rate was low (3.7%). In 61 biopsies where EM was completed, EM findings included foot process fusion (62%), endothelial cell swelling (38%), subendothelial lucencies (31%), and glomerular basement membrane duplication (41%). EM confirmed FSGS recurrence in three cases. In the remaining 58 cases, there was a positive yield of 31% where 18 biopsies were upgraded to a worse category after TG identification on EM. Kidney allograft outcome was poor regardless whether TG was detected early on EM or advanced on LM. Routine EM use in analyzing pediatric kidney transplant biopsies proved safe and provided valuable additional diagnostic information in almost one-third of cases. Additional studies are needed to determine if clinical interventions for early TG identified on EM can improve long-term outcomes.

Segmental Absence of Intestinal Musculature in a Child with Type IV Ehlers-Danlos Syndrome.

Patients with vascular Ehlers-Danlos syndrome (vEDS) have a defect in the formation of type III collagen. This defect puts patients at risk of vascular rupture, uterine rupture, and bowel perforations. The segmental absence of intestinal musculature is a rare histopathologic finding, wherein there is a lack of a muscularis propria layer in the intestinal wall. Although typically documented in the literature in neonates or adults, it can be seen in children of other ages. This is a case report of a patient who exhibits both rare entities, which has not been described in the literature to date.

Recurrence of granulomatous interstitial nephritis in transplanted kidney.

Sarcoidosis is a multisystemic disease of unknown etiology. Minor renal involvement is not rare but kidney failure is uncommon and only rare cases of recurrent disease in a kidney transplant have been published. We report a patient who at age 10 yr developed ESRD secondary to renal sarcoidosis with GIN. Her disease subsequently recurred in the transplanted kidney despite standard immunosuppression with prednisone, tacrolimus, and mycophenolate mofetil. The recurrent disease appeared to respond to increased immunosuppression, which included infliximab. However, the patient died of disseminated histoplasmosis three yr post-transplant.

Role of postnatal dietary sodium in prenatally programmed hypertension.

In this study we examined the short- and long-term impact of early life dietary sodium (Na) on prenatally programmed hypertension. Hypertension was induced in rat offspring by a maternal low protein (LP) diet. Control and LP offspring were randomized to a high (HS), standard (SS), or low (LS) Na diet after weaning. On the SS diet, the LP pups developed hypertension by 6 weeks of age. The development of hypertension was prevented by the LS diet and exacerbated by the HS diet. Kidney nitrotyrosine content, a measure of oxidative stress, was reduced by the LS diet compared with the HS diet. The modified diets had no effect on control pups. A group of animals on the SS diet was followed up to 51 weeks of age after an early life 3-week exposure to the HS or LS diet. This brief early exposure of LP animals to the LS diet prevented the later development of hypertension and ameliorated the nephrosclerosis observed after early exposure to the HS diet. The LP offspring with early exposure to LS diet had lost their salt-sensitivity when challenged with the HS diet at the age of 43-49 weeks. No effect of early life dietary Na was observed in control animals. These results show that hypertension in this model is salt sensitive and may, in part, be mediated by salt-induced renal oxidative stress and that there may exist a developmental window which allows postnatal "reprogramming" of the hypertension.

Infant acute lymphoblastic leukemia: a 20-year children's hospital experience.

We reviewed our 20-year experience with infant acute lymphoblastic leukemia (ALL). Nine infants (4.2% of all ALL) were identified; all were < 6 months of age. White blood cell counts ranged from 42,000-1.6 million/microL, 6 of 8 had hepatosplenomegaly, and 6 of 9 (66.6%) had central nervous system disease. Of 7 with cytogenetic information, 6 (85.7%) had diploidy; the remaining child was 47, XY,+8,del(21)(q22). Four had the MLL-11q23 abnormality. All received chemotherapy. Four underwent stem cell transplantation. Survival was 67%, (15 months-21 years). Deaths occurred at 9 months, 15 months (graft vs. host), and 7 years (complications of small bowel transplantation). Only 1 undergoing stem cell transplantation died. There were no late recurrences or second malignancies. Despite extensive disease and age < 6 months at diagnosis (a poor prognostic feature), for ALL patients our 67% survival is at least as good as reported, although it is less favorable than childhood ALL.

Right Ring Finger Volar Mass in a 14-Year-Old Boy.

A trigger digit is relatively uncommon in adolescents and often has a different etiology in that age group vs adults. In the pediatric population, trigger digits frequently arise from a variety of underlying anatomic situations, including thickening of the flexor digitorum superficialis or flexor digitorum profundus tendons, an abnormal relationship between the flexor digitorum superficialis and flexor digitorum profundus tendons, a proximal flexor digitorum superficialis decussation, or constriction of the pulleys. In addition, underlying conditions such as mucopolysaccharidosis, juvenile rheumatoid arthritis, Ehlers-Danlos syndrome, and central nervous system disorders such as delayed motor development have been associated with triggering. Less commonly, triggering secondary to intratendinous or peritendinous calcifications or granulations has been described, which is what occurred in the current case. This report describes a case of tenosynovitis with psammomatous calcification treated with excision of the mass from the flexor digitorum superficialis tendon and release of both the A1 and palmar aponeurosis pulleys in an adolescent patient. [Orthopedics. 2017; 40(5):e918-e920.].

Fibrous lipoblastoma with 8q11.2 abnormality.

A 3-month-old African American female infant had a rapidly growing lipoblastoma with a prominent fibrous component in the soft tissue of the left lateral knee, which recurred at 10 months. Cytogenetic analysis revealed deletion of 8(q11.2q13) with a 19(q12q13.3) insertion at that site, confirming that this is closely related to the conventional lipoblastoma. The presence of multivacuolated lipoblasts and the staining characteristics (no staining for CD99, CD34, or smooth muscle actin) distinguish this from the recently described lipofibromatosis.

Multimodal management of a pediatric cervical yolk sac tumor.

Even though vaginal bleeding is an unusual clinical presentation in infants and young children, thorough evaluation by the pediatric urologist requires the recognition and knowledge of less-common conditions, including malignancy. Extragonadal germ cell tumors are rare in children aged <15 years, representing approximately 1% of all cancers. Because of the close collaboration between pediatric oncologists and pediatric urologists, a multidisciplinary approach to the management and treatment of these tumors includes chemotherapy and surgical resection, aiming for fertility preservation when possible. We present a 10-month-old infant with a cervical or uterine germ cell tumor and the challenges found during her treatment.

Association of the T allele of an intronic single nucleotide polymorphism in the colony stimulating factor 1 receptor with Crohn's disease: a case-control study.

BACKGROUND: Polymorphisms in several genes (NOD2, MDR1, SLC22A4) have been associated with susceptibility to Crohn's disease. Identification of the remaining Crohn's susceptibility genes is essential for the development of disease-specific targets for immunotherapy. Using gene expression analysis, we identified a differentially expressed gene on 5q33, the colony stimulating factor 1 receptor (CSF1R) gene, and hypothesized that it is a Crohn's susceptibility gene. The CSF1R gene is involved in monocyte to macrophage differentiation and in innate immunity. METHODS: Patients provided informed consent prior to entry into the study as approved by the Institutional Review Board at LSU Health Sciences Center. We performed forward and reverse sequencing of genomic DNA from 111 unrelated patients with Crohn's disease and 108 controls. We also stained paraffin-embedded, ileal and colonic tissue sections from patients with Crohn's disease and controls with a polyclonal antibody raised against the human CSF1R protein. RESULTS: A single nucleotide polymorphism (A2033T) near a Runx1 binding site in the eleventh intron of the colony stimulating factor 1 receptor was identified. The T allele of this single nucleotide polymorphism occurred in 27% of patients with Crohn's disease but in only 13% of controls (X2 = 6.74, p < 0.01, odds ratio (O.R.) = 2.49, 1.23 < O.R. < 5.01). Using immunohistochemistry, positive staining with a polyclonal antibody to CSF1R was observed in the superficial epithelium of ileal and colonic tissue sections. CONCLUSIONS: We conclude that the colony stimulating factor receptor 1 gene may be a susceptibility gene for Crohn's disease.

Histologic differences in placentas of preeclamptic/eclamptic gestations by birthweight, placental weight, and time of onset.

With preeclampsia/eclampsia (PE/E), infants more often are either large or small for gestational age. We explored whether the differences in infant birthweight (BW), placental weights (PW), or time of onset are associated with histologic features of maternal vascular underperfusion. A retrospective chart identified 243 PE/E gestations between 2007 and 2010. Gestational age only was known at slide review. Investigated features included increased syncytial knots, villous agglutination, increased intervillous fibrin, distal villous hypoplasia, acute atherosis, mural hypertrophy of membrane arterioles, muscularized basal plate arteries, increased placental site giant cells, increased immature intermediate trophoblasts, infarcts, and villitis. The results were correlated with BW, PW, and onset time PE/E. One hundred thirty-eight PE/E gestations were identified with adequate slides and history. Increased BW placentas had decreased syncytial knots and increased mural hypertrophy of membrane arterioles. Decreased BW had increased placenta site giant cells. Increased PW had decreased distal villous hypoplasia. Decreased PW had increased syncytial knots, increased intervillous fibrin, and increased acute atherosis. Early-onset disease had increased syncytial knots, distal villous hypoplasia, villous agglutination, and infarcts. This suggests PE/E is not a single process resulting in a uniform distribution of lesions but, rather, is composed of several different processes manifesting a single clinical presentation.

Human Rabies with Initial Manifestations that Mimic Acute Brachial Neuritis and Guillain-Barré Syndrome.

INTRODUCTION: Human rabies can be overlooked in places where this disease is now rare. Its diagnosis is further confused by a negative history of exposure (cryptogenic rabies), by a Guillain-Barré syndrome (GBS) type of presentation, or by symptoms indicating another diagnosis, eg, acute brachial neuritis (ABN). CASE PRESENTATION: A 19-year-old Mexican, with no past health problems, presented with a two-day history of left shoulder, arm, and chest pain. He arrived in Louisiana from Mexico five days prior to admission. Of particular importance is the absence of a history of rabies exposure and immunization. On admission, the patient had quadriparesis, areflexia, and elevated protein in the cerebrospinal fluid, prompting a diagnosis of GBS. However, emerging neurological deficits pointed towards acute encephalitis. Rabies was suspected on hospital day 11 after common causes of encephalitis (eg, arboviruses) have been excluded. The patient tested positive for rabies IgM and IgG. He died 17 days after admission. Negri bodies were detected in the patient's brain and rabies virus antigen typing identified the vampire bat as the source of infection. CONCLUSION: Rabies should be suspected in every patient with a rapidly evolving GBS-like illness-even if there is no history of exposure and no evidence of encephalitis on presentation. The patient's ABN-like symptoms may be equivalent to the pain experienced by rabies victims near the inoculation site.

Pediatric epithelial salivary gland tumors: spectrum of histologies and cytogenetics at a children's hospital.

There are conflicting reports regarding the relative frequency of benign and malignant epithelial salivary gland tumors in children. There are only a few reports of the cytogenetic abnormalities in the pleomorphic adenomas (PA) that arise in children, and even less information regarding the pleomorphic adenoma gene 1 (PLAG1) and high motility group A2 (HMGA2 ) histochemical staining in PAs, or their correlation with histologic types (stromal vs epithelial predominance). A retrospective 14 year review of epithelial salivary gland tumors encountered at a children's hospital identified 13 tumors: 12 PAs and 1 acinic cell carcinoma (ACC). No mucoepidermoid carcinomas were identified. Tumors arose in the parotid (7) and other sites (2 submandibular, 4 minor). Ten PAs in our cohort had cytogenetic studies. Four were normal, 5 involved 8q12, and 1 involved 12q13. Immunohistochemistry identified an additional 2 PAs with PLAG1 staining, and 5 additional PAs with HMGA2 staining. One tumor with ins(18;8)(q21.1;q12q22.2) had no PLAG1 staining, but stained with HMGA2. This ins(18;8) may not have involved the PLAG1 gene. There was no demonstrable correlation of 8q12/PLAG1 staining or 12q13/HMGA2 staining with histologic type. Thus we found abnormalities in either 8q12/PLAG1 staining or 12q13/HMGA2 staining in all PAs. The HMGA2 staining in 50% of PAs suggests that it may be more frequently involved in PAs than previously thought based on cytogenetic studies, at least in children.

Mesangial hypercellularity in children: presenting features and outcomes.

Mesangial hypercellularity (MH), in the absence of sclerosis or immune deposition, was a common finding on renal biopsy in our center. We studied 66 children with predominant MH. Among all patients older than 2.7 years, blood pressure (BP) percentile and glomerular filtration rate (GFR) remained stable. Serum albumin (Alb) trended higher (3.0+/-0.2 start vs. 3.4+/-0.2 end g/dl, p=0.06) and urine protein/creatinine lower (4.2+/-0.9 start vs. 2.3+/-0.9 end mg/mg, p=0.18) at the end of the study period. The proportion with stage 1 CKD remained constant: 94% start vs. 92% end. At end, Alb was lower in patients referred for nephrotic syndrome (NS): 4.4+/-0.3 hematuria vs. 4.2+/-0.2 proteinuria vs. 2.8+/-0.3 NS g/dl, p<0.05 vs. both. Alb was lower (p=0.03) and urine protein/creatinine trended higher in patients with diffuse foot-process fusion (FPF). Twenty-five percent of patients with focal FPF developed NS, all had relapses, and 63% were steroid sensitive (SS). All but one with diffuse FPF presented with NS; 86% had relapses (mean 1 year) and 63% were SS. GFR trended higher at the end in those with matrix thickening (mat) (119.6+/-4.7 no mat vs. 129.1+/-2.6 mat ml/min per 1.73 m2, p=0.1). Those without mat were less SS (59% no mat vs. 80% mat) and were more likely to require alkylating agents (Alk) for NS. Among those with positive immunofluorescence (IF), 82% had immunoglobulin M (IgM) alone; those with positive IF were more SS and needed Alk for NS. MH predicts a favorable prognosis. FPF predicts NS and multiple relapses.

Pulmonary atresia, intact ventricular septum, right ventricle-dependent coronary artery circulation, and systemic collateral arteries supplying the left coronary artery.

We present a 14-day-old with pulmonary artery atresia with intact ventricular septum, right ventricle-dependent coronary circulation, a single aortic root coronary ostia (left), congenital collateral arterial supply to the left coronary artery from the left internal mammary artery, and bilateral paravertebral arteries, with obstructive coronary artery lesions.

Retroarterial colon with right-sided obstructive gangrenous colitis.

Retroarterial colon is a rare entity in which the colon is located behind the superior mesenteric vessels. Transmesenteric internal hernias result in portions of the bowel protruding through a defect in the mesentery and are often acquired but may be congenital. We report a 10-year-old female with trisomy 13 who lacked retroperitoneal fixation of the intestines and had a retroarterial transverse colon possibly resulting from a congenital transmesenteric internal hernia, that eventually lead to obstructive gangrenous colitis.