X-linked hypophosphatemic rickets: case report.

INTRODUCTION: X-linked hypophosphatemic rickets (XLHR) is a dominant inherited disease caused by isolated renal phosphate wasting and impairment of vitamin D activation. We present a girl with X-linked hypophosphatemic rickets (XLHR) as a consequence of de novo mutation in the PHEX gene. CASE OUTLINE: A 2.2-year-old girl presented with prominent lower limb rachitic deformity, waddling gait and disproportionate short stature (79 cm, < P5; -1,85 SD). On the basis of hypophosphatemia, hyperphosphaturia, high serum level of alkaline phosphatase, normal calcemia, 25(OH)D and PTH, as well as characteristic clinical and X-ray findings, diagnosis of hypophosphatemic rickets (HR) was made. Normal calciuria and absence of other renal tubular disorders indicated HR as a consequence of isolated hyperphosphaturia. The treatment (phosphate 55 mg/kg and calcitriol 35 ng/kg per day), introduced 15 month ago, resulted in a stable normalization of alkaline phosphatase and phosphorus serum levels (with intact calcemia and calciuria), disappearance of X-ray signs of the active rickets and improvement of the child's longitudinal growth (0.6 cm per month). Subsequently, by detection of already known mutation in the PHEX gene: c.1735G>A (p.G579R) (exon 17), XLHR was diagnosed. Analysis of the parental PHEX gene did not show the abnormality, which indicated that the child's XLHR was caused by de novo mutation of this gene. CONCLUSION: Identification of genetic defects is exceptionally significant for diagnosis and differential diagnosis of hereditary HR.

Pseudoachondroplasia: a case report.

INTRODUCTION: Pseudoachondroplasia (PSACH) is an autosomal dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein. It is characterized by rhizomelic dwarfism, limb and vertebral deformity, joint laxity and early onset osteoarthrosis. We present the girl with the early expressed and severe PSACH born to clinically and radiographically unaffected parents. CASE OUTLINE: A 6.5-year-old girl presented with short-limbed dwarfism (body height 79.5 cm, < P5;-32%) and normal craniofacial appearance and intelligence. The girl was normal until 3 months of age when she expressed growth retardation with apparently shorter extremities in relation to the torso. With age, her rhizomelic dwarfism became increasingly visible, and since completed 15 months of age, when she started to walk, the disease was complicated with genu varum, lumbar lordosis and abnormal gait. Beside visibly short forearms, short, broad and ulnar deviation of the hands, brachydactyly and joint hyperlaxity, the radiographic picture showed markedly flared metaphyses, small and irregular epiphyses and poorly formed acetabulum. CONCLUSION: PSACH is an achondroplasia-like rhizomelic dwarfism recognized by the absence of abnormality at birth, normal craniofacial appearance, characteristic epiphyseal and metaphyseal radiographic finding and joint hyperlaxity.

Indications and results of renal biopsy in children: a 10-year review from a single center in Serbia.

BACKGROUND: This study was conducted to retrospectively investigate the indications for renal biopsy in native kidneys and to analyze pathological findings in the last 10 years in a single tertiary pediatric hospital in Serbia. METHODS: All patients who underwent renal biopsy at our hospital between 2001 and 2010 were included in the present study. Renal biopsy was performed under fluoroscopy with a biopsy gun. All renal biopsies were studied under light and immunofluorescent microscopy, while electron microscopy was rarely performed. RESULTS: The study group included 150 patients (56% female) who underwent 158 percutaneous native kidney biopsies. Median age was 11.5 years (range 0.2-20 years). The most frequent indications for renal biopsy were nephrotic syndrome (32.9%), asymptomatic hematuria (23.4%), urinary abnormalities in systemic diseases (15.8%) and proteinuria (11.4%). Primary glomerulonephritis (GN) was the most common finding (57.4%), followed by secondary GN (15.5%) and tubulointerstitial diseases (4.5%). According to histopathological diagnosis, the most common causes of primary GN were focal segmental glomerulosclerosis (20.9%), mesangioproliferative GN (14.6%), IgA nephropathy (8.9%) and minimal change disease (13%). Lupus nephritis (6%) and Henoch-Schönlein nephritis (4%) were the most common secondary glomerular diseases. CONCLUSIONS: The epidemiology of glomerular disease in our single-center report is similar to that in data from adjacent Croatia and Greece. Focal segmental glomerulosclerosis was the dominant histopathological finding, followed by mesangioproliferative GN and IgA nephropathy.

Association of hereditary elliptocytosis and Gilbert's syndrome as the cause of biliary calculosis: case report.

INTRODUCTION: Biliary calculosis is rare in children. It occurs associated with different haemolytic and non-haemolytic disorders, which are sometimes also combined. CASE OUTLINE: A 15-year-old male was hospitalized due to biliary calculosis and non-conjugated hyperbilirubinemia. A mild non-conjugated hyperbilirubinemia, without anaemia and other symptoms of liver dysfunction, was registered at age 8 years, and 7 years later cholelithiasis with transitory choledocholithiasis. The finding of ellyptocytes in blood smear, which was also verified in mother, normal haemoglobin count and the absence of diseases followed by secondary dysmorphic erythrocytes of this type, indicated a clinically milder (compensated) hereditary ellyptocytosis, while more than a double increase of non-conjugated serum bilirubin fracture after a three-day hypocaloric diet (400 kcal per day) showed the concurrent presence of Gilbert's syndrome. In the laparascopically removed gallbladder a larger number of small pigmented calculi were disclosed. CONCLUSION: Gilbert's syndrome is an essential precipitating factor of biliary calculosis in patients with chronic haemolytic condition. Thus, in all cases of biliary calculosis and non-conjugated hyperbilirubinemia with absent clinical and laboratory parameters of liver disorders and anaemia, except in compensated haemolytic disease and Gilbert's syndrome as isolated disorders, a possibility of their association should be taken into consideration.

Minimally invasive inguinal technique for the management of duplex ureteric anomaly.

OBJECTIVE: To present outcomes of a minimally invasive inguinal technique for the separation of the distal part of ureters in duplex systems and for the extravesical ureteroneocystostomy of only the pathologically involved ureter. MATERIALS AND METHODS: From November 2001 to February 2007, we performed extravesical reimplantation of only the involved ureter in 21 duplex systems, of which 14 were refluxing (megaureters) and seven had obstruction of the ureterovesical junction. The mean (range) age of the patients was 39 (17-59) months. In seven patients, ureterocutaneostomy (of the involved ureter only) was performed first, with reimplantation 3-6 months later, after the diameter of the ureter had decreased, to ensure safe reimplantation. The mean (range) postoperative follow-up was 28 (12-47) months. RESULTS: Postoperative voiding cysto-urethrograms (VCUGs) and magnetic resonance imaging (MRI), showed an absence of vesico-ureteric reflux (VUR) or obstruction in the ureters of the first 10 patients. In the remaining 11 patients, there was no ultrasound detectable dilatation, but symptomatic urinary tract infection developed in two of these patients. Subsequent VCUG and MRI results showed no obstructions or VURs. CONCLUSION: Our results showed that the minimally invasive inguinal approach to separation of ureters in duplex systems and single ureteroneocystostomy of only the pathologically involved ureter represents a viable treatment option.

Ruptured intramural intestinal hematoma in an adolescent patient with severe hemophilia A.

We report on a 17-year-old patient with severe hemophilia A without inhibitors who developed abdominal bleeding after an episode of severe cough. Abdominal ultrasound showed intramural intestinal hematoma as well as large amount of peritoneal fluid appearing as blood and right hematocele. Abdominal CT revealed markedly thickened intestinal wall in sigmoidal region. Patient was managed with replacement therapy as well as peritoneal drainage with favorable outcome. This is the first report on a hematoperitoneum in a hemophiliac due to ruptured intramural sigmoidal hematoma.

[Clinical characteristics and survival of children with hepatoblastoma--single centre experience].

INTRODUCTION: Hepatoblastoma is the most frequent malignant liver tumour of childhood and it accounts for 1% of all paediatric cancers. The outcome is significantly improved by introducing intensive chemotherapy regimens followed by complete surgical tumour resection. The long-term survival is 75-95% at present. OBJECTIVE: To summarize clinical characteristics and treatment results in children with hepatoblastoma. METHOD: The patients diagnosed with hepatoblastoma and treated at the Department of Haematology of the University Children's Hospital in Belgrade, between January 1995 and December 2007 were retrospectively analysed. We analysed mode of therapy, surgical management and patients' survival according to Kaplan Mayer statistical test. RESULTS: Eleven patients were treated (ten boys and one girl), aged from 6 months to 13 years, mean 32 months, median 12 months. The most frequent presenting sign was abdominal distension. Routine laboratory examination showed elevated alpha-fetoprotein (AFP), range 147 to 44880 ng/ml, mean 8667 ng/ml.Ten patients (91%) had elevated platelet count, range 450 to 909 x 10(9)/l. Initial lung metastasis developed in 3 patients (27%).The diagnosis was established by an open surgical biopsy in 6 patients and after complete tumour resection in 4 patients, namely 2 patients after preoperative chemotherapy and in 2 patients with no previous chemotherapy. Histopathology verified hepatoblastoma in 10 patients: in 7 patients with epithelial type and in 3 patients with mixed epithelial-mesenchyme type. Six patients were in continuous remission with mean follow up of 58 months. One patient was lost to follow up. Four patients died; three patients due to disease progression and one patient due to sepsis after the first cycle of chemotherapy. CONCLUSION: Combined preoperative chemotherapy with complete tumour resection followed by postoperative chemotherapy results in a high percentage of definitive cures.

[Gigantic ovarian and suprarenal cysts ten years after enucleation of unilateral retinoblastoma].

INTRODUCTION: Retinoblastoma (RB) is the most common eye tumour in children and is curable. Patients with hereditary RB have increased risk of developing additional tumours, predominantly sarcomas. The published results on the treatment of bilateral RB have shown that 10-15% of patients develop second primary tumours (SPT). Average latent period, e.g. the period from the diagnosis of bilateral RB to the appearance of SPT is 10.4 years. In the literature, the appearance of second benign tumours in patients suffering from unilateral and bilateral RB has not been analyzed separately. However, the size and the location of benign tumours can cause serious complications. CASE OUTLINE: We present a 14-year-old female patient. At age 4 years, her left eye was enucleated owing to unilateral RB. In the postoperative period, she did not undergo irradiation, nor did she receive chemotherapy. On her regular ophthalmologic check-up, the patient informed us that her belly was "swelling" over the past four months. She had no pains or other complaints. The abdomen was significantly above the level of the chest, tense, painless on palpation, with obvious fluctuations. Abdominal echosonography confirmed the presence of a huge multilocular cystic formation, 19 x 18 cm in diameter, spreading from the pelvis to the epigastrium, and pressing the liver and spleen. A cyst of 4.7 cm in diameter was observed in the upper pole of the left kidney. Both the gigantic cyst of the left ovary (weighing 10300 g) and the left suprarenal cyst (weighing 30 g) were removed. CONCLUSION: We report a patient who developed second non-ocular tumours (ovarian and suprarenal cysts) after successful treatment of unilateral RB. Patients treated for RB (hereditary and non-hereditary) should be checked regularly and meticulously. Early recognition of tumours, treatment can prevent possible complications.

[Treatment of psoas haematoma in a patient with haemophilia and inhibitors].

INTRODUCTION: Particular problem in treating haemophiliacs with serious muscle bleeding such as iliopsoas haematoma, are patients with inhibitor. CASE OUTLINE: Our study describes three episodes of psoas haematoma in a patient with haemophilia and inhibitor successfully treated with recombinant activated factor VII (rFVIIa). CONCLUSION: Based on our experience, initiating therapy within two hours in our patient, contributed to successful treatment, although small cumulative doses of rFVIIa were used. Therefore, introducing home treatment along with adequate patient and family education similar to developed countries becomes imperative in our environment, not only for providing better quality of life, but also from pharamaco-economic point of view.

Myeloid sarcoma presenting with bilateral proptosis and kidney infiltration.

The authors describe a male infant with a history of transient pancytopenia who developed progressive bilateral proptosis associated with diffuse infiltration of the kidney and normal bone marrow. The histopathological examination of the kidney revealed diffuse infiltration of cells of myeloid origin with monocytic differentiation. Although orbital involvement by myeloid sarcoma, with or without concurrent acute myeloid leukemia, is well known, there are distinctive features in this patient that are not reported in the literature, namely bilateral proptosis and simultaneous presence of bilateral kidney infiltration, which enabled diagnosis.

[Renal transplantation again at the University Children's Hospital of Belgrade].

After a 15-year break, pediatric renal transplantation restarted again at the University Children's Hospital of Belgrade. Owing to this, best relationship between the number of new patients with terminal renal failure and those with functioning graft has been recently achieved, and mortality of children with terminal renal failure has been decreased to zero. The aim of this paper was to show the recent results achieved in pediatric renal transplantation at the University Children's Hospital in Belgrade. During the period from June 2001 till June 2003, 10 patients, 6 boys and 4 girls, aged 5 to 15 years (9.5+/-3.8) underwent transplantation of kidney harvested from a live matched donor. Out of these, two patients underwent pre-emptive transplantation. Urine from the graft started immediately after anastomosis was performed, while serum creatinine normalized after 15 to 120 hours. Daclizumab was the most commonly used as immunosuppressive induction agent, but the maintenance immunosuppressive therapy consisted of Imuran or Mycophenolate Mofetil (MMF), Neoral or Tacrolimus (FK 506) and prednisone. At the end of follow up, after 18.7+/-8.4 months, nine patients had normal, and one patient slightly decreased renal graft function. Growth after transplantation and nutritional status were improved in all patients, and all of them achieved complete psychosocial rehabilitation. These results showed that the University Children's Hospital in Belgrade fulfilled all necessary conditions to become a specialized Center for Pediatric Renal Transplantation.

[Surgical management of developmental lung anomalies]. / Hirursko lecenje razvojnih anomalija pluca.

Prenatal diagnosis allows for insight into the evaluation of fetal lung anomalies. Serial ultrasonographic studies of fetuses helped in evaluation and definition of the natural course of these lesions as well as necessity for fetal therapy. It has been found that the overall prognosis depends on the size of the lung mass and the secondary derangement of normal lung tissue and cardiovascular system. Although much is known about the prenatal course of these anomalies, little is known about the postnatal course of asymptomatic patients. Infants who are symptomatic at birth require early surgical treatment. During the period from 1984-2003, 23 patients with congenital lung anomalies were treated, out of whom 19 were diagnosed postnatally and 4 prenatally. All postnatally diagnosed patients (9 congenital lobar emphysema, 5 congenital cystic adenomatoid malformations, 3 pulmonal cysts, 1 bronchopulmonary sequestration and 1 arteriovenous malformation) underwent surgical excision (lobectomy or sequestrectomy) after becoming symptomatic (main symptoms were infection or respiratory distress). Prenatally diagnosed patients (2 bronchopulmonary sequestrations and one enteric mediastinal cyst) underwent elective surgical interventions (sequestrectomy and excision of the cyst) in infancy. Postoperative course was uneventful in all patients. One patient probably had spontaneous involution of the mass. We believe that elective resection is indicated in asymptomatic neonates with congenital lung anomalies, because of the potential risk of infection and occult malignant transformation. Early resection also maximizes compensatory lung growth. This approach eliminates any risk of pulmonary infection, lung abscess formation or malignant transformation. In addition, subsequent exposure to radiation will be avoided.

[Conservative treatment of hypertrophic pyloric stenosis in children]. / Konservativno lecenje hipertroficne stenoze pilorusa kod dece.

INTRODUCTION: Hypertrophy of the pylorus causing obstruction of the gastric outlet, or infantile hypertrophic pyloric stenosis (IHPS), is the most common indication for abdominal surgery in infancy. The incidence of the condition is 3-4 per 1000 live births, and male infants are affected more often than females, in 4:1 ratio. Vomiting, as the first symptom, most often occurs between the third and fourth week after birth, rarely after second month, but there have been few reports of vomiting as late as 5 months. Etiology of IHPS is still controversial. Two theories have been quoted most: absence of non-adrenergic and non-cholinergic nerve fibers which are mediators of smooth muscle contraction, and absence of nitric oxide inhibitory innervation of pyloric smooth-muscle resulting in unopposed contraction of the sphincter in response to muscarinic stimulation. Atropine sulfate is known to inhibit acetylcholine competitively in neuroreceptors, acting peripherally as a competitive inhibitor of the muscarinic effects of acetylcholine, leading to decreased gastrointestinal peristalsis. This action is believed to be important in IHPS cases. AIM: The aim of this paper is to provide further information on potential role of atropine in the management of patients with IHPS. METHODS: From April 2000 to October 2002, 22 patients (16 boys and 6 girls), aged 21 days to 3 months, with IHPS were treated by oral administration of atropine sulfate in our institution. Diagnosis of IHPS was based on US examination in all cases. A nasogastric tube was inserted and left in situ. Medical treatment involved initial correction of fluid and electrolyte imbalance combined with oral administration of atropine sulfate. Atropin was given in the form of aqueous solution in initial dose of 0.05 mg/kg/d. The total daily dose was divided into 8 equal doses. Each dose was formulated to be given in a volume of 1 ml. Before the administration of each dose of atropine, stomach was decompressed by suction via nasogastric tube. The infant was placed on the right side with the head on the cot elevated 20 degrees to 30 degrees for 15 to 30 minutes after each atropine dose. Oral feeding with 10 ml of 10% glucose was then attempted. If feeding was tolerated, the same dose of atropine was administered 3 hours later, followed by a trial of 20 ml of 10% glucose. If tolerated, 10 ml of conventional formula was then tried after atropine administration 3 hours later. The volume of formula was then increased 10 ml per feed until full feeding (120 ml/kg/d) was tolerated. Dribbling (2-3 times per day) was ignored. If vomiting occurred, the same dose of atropine, volume and type of feed, were tried again 3 hours later, and if still not tolerated, atropine was increased by 1 microg/kg/dose without increasing the volume of feed. This approach was repeated until oral feeding was tolerated at least twice, and only then the volume of oral feed was increased. During night shift (between 11 p.m. and 5 a.m.), atropine concentration and amount of oral feed were not increased. If vomiting recurred, the volume of oral feed was decreased to the last tolerated volume and maintained until the following day. Oral atropine was increased until predetermined maximum oral dose (0.1 mg/kg/d) was reached. If oral administration of atropine was ineffective, a decision to perform pyloromyotomy was made no later than 7 days after commencement of oral atropine. RESULTS: Atropine had effect (vomiting frequency less than twice per day) on average 3.29 days (range 1-7 days) from commencement. Oral atropine was tolerated very well, and was effective in 18 cases. Four cases were referred to pyloromyotomy, on day 4 (2 patients), day 5 (1 patient) and on day 6 (1 patient) of atropine treatment. Therapy was continued until US showed normalization of pyloric muscle thickness, passage of food through wide pyloric channel and until patients started gaining weight. Average duration of therapy was 24.05 days (11-39 days). Neither of patients from our group was treated with intravenous atropine sulfate. DISCUSSION: Although intravenous atropine is more effective (as shown by Nagita et al), there is an increased incidence of side effects such as flushing and tachycardia. Oral atropine has been used successfully by other teams without side effects, and there were no side effects or complications related to the use of atropine in this study. Prospective, randomized study comparing outcomes of medical versus surgical management of IHPS in our hospital has been currently in progress and will provide further information on potential role of atropine in the management of patients with IHPS. CONCLUSION: We believe it is unlikely that oral or intravenous atropine will ever replace surgery for IHPS, but it may be a good alternative to pyloromyotomy, particularly in children with major concurrent primary disease, or when parents are not enthusiastic about surgery in so young children.