Comprehensive genetic testing in children with a clinical diagnosis of ARPKD identifies phenocopies.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is genetically one of the least heterogeneous ciliopathies, resulting primarily from mutations of PKHD1. Nevertheless, 13-20% of patients diagnosed with ARPKD are found not to carry PKHD1 mutations by sequencing. Here, we assess whether PKHD1 copy number variations or second locus mutations explain these cases. METHODS: Thirty-six unrelated patients with the clinical diagnosis of ARPKD were screened for PKHD1 point mutations and copy number variations. Patients without biallelic mutations were re-evaluated and screened for second locus mutations targeted by the phenotype, followed, if negative, by clinical exome sequencing. RESULTS: Twenty-eight patients (78%) carried PKHD1 point mutations, three of whom on only one allele. Two of the three patients harbored in trans either a duplication of exons 33-35 or a large deletion involving exons 1-55. All eight patients without PKHD1 mutations (22%) harbored mutations in other genes (PKD1 (n = 2), HNF1B (n = 3), NPHP1, TMEM67, PKD1/TSC2). Perinatal respiratory failure, a kidney length > +4SD and early-onset hypertension increase the likelihood of PKHD1-associated ARPKD. A patient compound heterozygous for a second and a last exon truncating PKHD1 mutation (p.Gly4013Alafs*25) presented with a moderate phenotype, indicating that fibrocystin is partially functional in the absence of its C-terminal 62 amino acids. CONCLUSIONS: We found all ARPKD cases without PKHD1 point mutations to be phenocopies, and none to be explained by biallelic PKHD1 copy number variations. Screening for copy number variations is recommended in patients with a heterozygous point mutation.

Voiding urosonography with second-generation contrast agent versus voiding cystourethrography.

Contrast-enhanced voiding urosonography (VUS) is becoming more widely used for the diagnosis of vesicoureteric reflux (VUR). The purpose of this study was to evaluate the sensitivity of VUS using a second-generation ultrasound (US) contrast agent and compare it with standard fluoroscopic voiding cystourethrography (VCUG). A total of 183 children with 366 kidney-ureter units (KUUs) underwent VUS and VCUG in the same session with the same catheterization. VUS was performed after intravesical administration of 1 ml of a second-generation ultrasound contrast agent (UCA; SonoVue, Bracco, Italy). VUR was detected in 140 out of 366 cases (38%); in 89 (24.3%) by both methods, in 37 (10.1%) by VUS only, and in 14 (3.8%) by VCUG only. Although there was considerable agreement in the diagnosis of VUR by VUS and VCUG (κ=0.68, standard error [κ]=0.04), the difference in the detection rate of reflux between VUS and VCUG was significant (p<0.00001). The grade of VUR detected with VUS showed moderate agreement with grading by VCUG. Our findings suggest that contrast-enhanced harmonic VUS using a second-generation contrast agent is superior to VCUG in the detection and grading of VUR, and it should be the method of choice for this clinical indication.

[Application of enteral and "individual" parenteral nutrition therapies in pediatric patients]. / Enterális és "egyedi" parenterális táplálási terápia alkalmazása a gyermekgyógyászatban.

In long-standing stress situation, in malabsorption syndromes we cannot provide the adequate protein and energy intake with enteral nutrition, so we often have to add complementary parenteral feeding. Using combined enteral and "individualised" parenteral nutrition the quality of life improves, the time of hospital stay decreases. The parenteral nutrition of neonates and infants implies a great challenge for health care supplier; there is no available "All-in-One" mixture infusion below 2 years of age. We developed a new chart for parenteral nutrition, which can be modified easily according to the patient's age, body weight, need. This chart was introduced to the "Guidelines of the Infant and Pediatric Board" in 2003 and accepted by the Health Ministry in 2006. The Central Pharmacy of the Semmelweis University prepares the "individualised" parenteral mixture in laminar air-flow box, in aseptic condition. Further advantage of the Infusion Mixture, that 4-day portion can be prepared. We review the usefulness and the development of combined enteral and "individualised" parenteral nutrition. Altogether we had 30 patients needing total parenteral nutrition (TPN) in the last 5 years: 46% short bowel syndrome, 18% oesophageal disorders, 15% oncology patients, 21 % septicaemia and other disorders. Beside the "individualised" parenteral nutrition the use of enteral formulas increased, too. Our goal is the optimal combination of parenteral and enteral nutrition in order to diminish the hospital stay and to improve the quality of life of our patients.

[Vena portae obstruction as a cause of portal hypertension in a child with Turner syndrome]. / A vena portae elzáródása miatt kialakult portalis hypertensio Turner-szindrómás gyermekben.

Cardiovascular and renal malformations are well-known in Turner syndrome. However, gastrointestinal bleeding is less frequent. The possible etiologies of gastrointestinal bleeding in Turner syndrome are intestinal teleangiectasia, inflammatory bowel disease and portal hypertension. The authors report a 3-year-old girl with Turner syndrome who presented with severe gastrointestinal bleeding requiring transfusion. The radiological examination indicated prehepatic portal hypertension as a reason for haematochezia. The liver biopsy demonstrated the anomaly of intrahepatic arteries and veins. In this report we describe a case of congenital portal vein obstruction and we reviewed liver abnormalities associated with Turner syndrome and causes of obstruction of vena portae in childhood.

[Multicystic dysplastic kidney: natural history of the affected and the contralateral kidney compared to the normal and solitary kidney]. / Multicystás dysplasiás vese: kórlefolyás, az ellenoldali vese növekedésének összehasonlítása a solitaer és a normális vese növekedésével.

INTRODUCTION: Complications of multicystic dysplastic kidney are rare, but hypertension and malignant transformation represent real danger. PATIENTS/METHODS: In a 10-year period, 94 infants (60 boys, 34 girls) with multicystic dysplastic kidney were diagnosed. The data obtained from these patients were compared to 70 children with solitary kidney of which 36 were newborns. In 80 cases (85%) the diagnosis of multicystic dysplastic kidney was already suspected by prenatal sonography. RESULTS: Abnormalities of the contralateral kidney were found in 15 of the 94 patients (16%). Complete involution of the multicystic dysplastic kidney was observed in 19, and a decrease in size in 42%. In 37 children (39%) the dysplastic kidney has been removed at the age of about 1 year because of no involution. The length of the contralateral kidney, compared to the normal standard was already significantly larger at birth. In newborn babies with unilateral renal agenesia the solitary kidney was also significantly longer. CONCLUSIONS: Compensatory hypertrophy of single functioning kidneys occurs in utero both in patients with multicystic dysplastic kidney and in those with unilateral renal agenesia. Based on the results of these and previous studies, early nephrectomy cannot be recommended in the newborn period. Surgery remains an option for patients who have no involution at the time of about 1 year of age.

[Infantile acute lobar nephritis]. / Csecsemókori akut lobaris nephronia.

INTRODUCTION: Acute lobar nephronia is a focal interstitial inflammation of the kidney healing well on conservative therapy. OBJECTIVE: Authors call attention on this rare pathological entity and emphasize the role of the imaging modalities in making the diagnosis. Short literature review is also given. PATIENT AND METHODS: An 11 months old babyboy presented with febrile seizure and palpable right flank mass. Abdominal sonography and CT were done. RESULTS: Urine analysis gave evidence of upper urinary tract infection. Hyperechogenic solid mass in the right kidney was seen on sonography. Diagnosis of infection suspected on sonography has been confirmed by abdominal CT scan and possibility of tumor has been ruled out. Acute lobar nephronia was diagnosed and the patient has been treated successfully with antibiotics. CONCLUSION: Acute lobar nephronia may mimic both abscess and tumor. Differential diagnosis is very important because treatment of acute lobar nephronia is nonsurgical.

[Malignant rhabdoid tumour in the liver]. / Malignus rhabdoid tumor a májban.

The authors describe the case of a 6-months-old child with liver tumour. The newborn was healthy until 6 months of age. Prior to hospitalization meteorism and remarkably enlarged liver were observed. A tumour occupying the right lobe of the liver was found with ultrasound and computer tomography, which proved to be inoperable. Intraoperative liver biopsy and few days later the autopsy histology showed a malignant rhabdoid tumour. Authors describe the clinical and morphological features of a rare case of primary hepatic rhabdoid tumour.

[Urinary enzyme excretion in childhood uropathy]. / Obstruktív uropathiás gyermekek enzimürítése.

INTRODUCTION: Renal tissue, and tubules are rich in enzymes but enzyme measurement in the urine as diagnostic parameters in renal diseases have not yet been generally accepted as routine procedures. AIMS: To study urinary enzyme excretion in childhood obstructive uropathy and compares the diagnostic efficiency of them. METHODS: Excretion of the enzymes alkaline phosphatase (ALP), gamma-glutamyltransferase (gamma-GT), N-acetyl-beta-D-glucosaminidase (NAG) and leucine aminopeptidase (LAP) has been investigated in urine of 34 children suffering from obstructive uropathy and in 31 healthy controls by photometric kinetic analysis using synthetic substrates. RESULTS: Urinary excretion of both enzymes significantly increase--2-10 times higher than normal controls--indicates tubular damage. In this study the following relations were found in specificity and in sensitivity: ALP < LAP < gamma-GT < NAG. CONCLUSIONS: Elevated urinary enzyme excretion may be helpful in identifying upper tract obstruction, which if left untreated may cause progressive renal deterioration. It has a role in helping to determine the surgical correction or can be safely followed without fear of parenchymal damage.