Novel NLRC4 Mutation Causes a Syndrome of Perinatal Autoinflammation With Hemophagocytic Lymphohistiocytosis, Hepatosplenomegaly, Fetal Thrombotic Vasculopathy, and Congenital Anemia and Ascites.

Autoinflammatory diseases are caused by pathologic activation of the innate immune system. Primary hemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome of excessive immune activation caused by monogenic mutations resulting in cytotoxic cell defects and subsequent failure to eliminate activated macrophages. Secondary HLH is often diagnosed in cases without a known Mendelian inheritance. However, some cases of "secondary" HLH have been shown to harbor mutations with partial dysfunction of the cytotoxic system. Recently, macrophage intrinsic abnormalities caused by NLRC4 inflammasome mutations have been linked to autoinflammation and recurrent macrophage activation syndromes resembling a primary HLH. We report a case of a former 28-week preterm infant with congenital anemia, ascites, and a heavy edematous placenta with fetal thrombotic vasculopathy, who developed hepatosplenomegaly and unexplained systemic inflammation with laboratory features of HLH in the early postnatal course and died at 2 months of age. Postmortem examination confirmed the hepatosplenomegaly with marked sinusoidal hemophagocytosis, along with striking hemophagocytosis in the bone marrow and lymph nodes. There was extensive acute and chronic ischemic bowel disease with matted bowel loops, fibrous adhesions, and patchy necrotizing enterocolitis features. Whole exome sequencing analysis demonstrated a novel mosaic heterozygous NLRC4 512 C> T (p.Ser171Phe) de novo mutation predicated to cause a dominant, gain-of-function mutation resulting in a constitutively active protein. The assembly of NLRC4-containing inflammasomes via an induced self-propagation mechanism likely enables a perpetuating process of systemic macrophage activation, presumed to be initiated in utero in this patient.

Fetal ascites and hydrometrocolpos due to persistent urogenital sinus and cloaca: a rare congenital anomaly and review of literature.

Fetal ascites can occur due to many heterogeneous disorders. Its association with hydrometrocolpos because of persistent urogenital sinus and cloaca is extremely rare. A 29-year-old primigravida presented at 32 weeks of gestation with ultrasonographic evidence of fetal ascites, a cystic pelvic mass, hydronephrosis and oligohydramnios. Fetal ascites in this case was due to fetal urine draining through fallopian tubes into the abdomen as a result of vesicovaginal fistula and distal vaginal atresia. The antenatal ultrasound results along with autopsy findings are discussed. Though rare, a persistent urogenital sinus is to be suspected in isolated fetal ascites cases where the viral tests are negative and there is no evidence of cardiac anomalies as this is a treatable anomaly if diagnosed at early gestational age.

Congenital ascites due to hepatoblastoma with extensive peritoneal implantation metastases in a premature equine fetus.

A premature dead equine fetus with excessive fluctuating distension of the abdomen was delivered by extraction. Post-mortem examination revealed ascites and a solitary, irregular, bulging, multinodular, firm, yellow mass of 25 cm in diameter in the right liver lobe. Extensive peritoneal implantation metastases were present. The masses were composed of polygonal embryonal cells arranged in sheets and nests. Based on the immunohistochemical expression of Ki67, low molecular weight cytokeratin and alpha-1 fetoprotein, a diagnosis of hepatoblastoma with peritoneal implantation metastases was made.

Ruptured remnant of urachal diverticulum: an unusual cause of congenital urinary ascites.

Urachal diverticulum is an infrequent finding and its perforation as a cause of fetal urinary ascites has not been reported before. This is a case report on an infant with antenatal diagnosis of fetal ascites. This infant was delivered via cesarean section and needed mechanical ventilation owing to a massive ascites that required paracentesis. She did not void for 20 h until a urethral catheter was placed. The biochemical analysis of the ascitic fluid compared with the serum and urine was suggestive of urine ascites. The voiding cystourethrogram (VCUG) showed a leakage at the remnant of urachal diverticulum. The urethral catheter was maintained for 3 weeks until the repeated VCUG confirmed a sealed-off urachal diverticulum. With removal of the catheter, the infant was able to void spontaneously and was discharged home on continued prophylactic antibiotics. As symptomatic urachal remnants have an increased potential for malignant transformation, a close follow-up by a urologist was recommended.

Neonatal ascites and oligohydramnios: the role of kidney.

Posterior urethral valve pathologies are the most frequent childhood obstructive uropathy reported, and we infer their presence on diagnosing foetal ascites and oligohydramnios. Early action is vital to determine the long-term development and the degree of impairment of renal function. We report a newborn male 34 weeks of gestation with a prenatal diagnosis of foetal ascites, fluid on the loose in renal fossa and oligohydramnios. Subsequent studies have shown the presence of posterior urethral valves with associated significant vesicoureteral reflux. There was no secondary renal damage. Intrauterine decompression of the urinary tract seems to have exerted a protective role against kidney damage. This finding supports the role of foetal decompression surgery in early and severely obstructive forms to improve the prognosis of renal function in the long term.

Congenital monoblastic leukemia presenting as jaundice, pleural effusion, and ascites: case report and literature review.

Congenital leukemias are a rare group of hematologic neoplasms with a wide range of clinical signs and symptoms. Here we reported a neonate presenting with jaundice, pleural effusion and ascites. The total protein and serum albumin were markedly low at 48 and 12 g/L. Computerized tomography showed the density of liver was asymmetry with several hypoechoic regions. Initial blood routine examination revealed only thrombocytopenia while blood white cells increased to 30.0×10(9)/L with 17% blast cells several days later. Bone marrow biopsy showed the proportion of blasts and promonocytes increased and she was diagnosed as acute monoblastic leukemia.

Prenatal ultrasonographic features of persistent urogenital sinus with hydrometrocolpos and ascites.

OBJECTIVE: Hydrometrocolpos is a rare congenital disorder very rarely reported on prenatal sonography. In this study we report a persistent urogenital sinus with hydrometrocolpos and ascites at 24 weeks of gestation. CASE: Detailed ultrasonographic examination revealed female fetus with pelvic mass measured as 60 x 70 x 80 mm, anterior to sacral bone and inferior to bladder, and ascites, ureterocele, hydroureter, hydronephrosis but normal amniotic fluid. Further examination showed that cervical canal and uterine cavity was in continuation with the pelvic mass and dilatation of uterine tubes implicated hydrometrocolpos. Physical examination of the neonate revealed a single anterior opening at perineum and a patent anus but no visible urethral orifice. A voiding cystourethrogram demonstrated a urethrovaginal fistula. The neonate underwent ureteroneoostomy and was discharged on day 10 for follow-up and final repair. CONCLUSION: Prenatal ultrasonographic diagnosis of hydrometrocolpos in our case prevented unnecessary interventions and allowed early neonatal treatment.

In utero diagnosis of bladder perforation with urinary ascites. A case report.

Prenatal sonographic diagnosis of fetal obstructive uropathy is relatively common. However, the complication of spontaneous rupture of the obstructed bladder in utero causing fetal urinary ascites is extremely rare. This case report describes an unusual case of congenital bladder perforation and urinary ascites diagnosed in utero. The pertinent literature is reviewed.

Management of urinary extravasation in 18 boys with posterior urethral valves.

PURPOSE: Urinary extravasation with associated posterior urethral valves is uncommon and published articles are restricted to case reports. We propose a management algorithm on the basis of presentation of 18 boys with this condition. MATERIALS AND METHODS: In this retrospective review we analyze the clinical features, diagnostic radiological imaging (voiding cystourethrogram and (99m)technetium mercaptoacetyltriglycine scan) and measured glomerular filtration rate (GFR) for assessment of renal function in boys presenting with posterior urethral valves and urinary extravasation. Indications for surgical intervention and long-term outcome were evaluated. Results are presented as mean +/- SD. RESULTS: Patient age at presentation was 4 days (range 1 to 28). Salient features at presentation were abdominal distention in 55.5% of cases, flank mass in 55.5%, respiratory distress in 16.6% and septicemia in 22.2%. Patients were categorized into group 1 with ascites (6 boys) and group 2 without ascites (12). Followup was 70.8 +/- 5.6 months. In group 1 the 3 boys with ascites alone had a followup GFR of 29 versus 74 ml. per minute per 1.73 m.2 in 3 with urinoma plus ascites (p = 0.001) at 64 +/- 4.9 months. In group 2 the GFR in 3 boys with bilateral urinoma was 104.7 +/- 30.4 versus 54.3 +/- 29.4 ml. per minute per 1.73 m.2 in the other 9 with unilateral urinoma (p = 0.001) at 36 +/- 4.2 and 81.3 +/- 4.7 months, respectively. The ipsilateral kidney showed reduced function in 6 of 12 boys with unilateral urinoma from both groups. CONCLUSIONS: Renal function on the side of the urinoma is impaired, and the majority of patients have impaired global renal function. A management algorithm is proposed.

Development of renal function after neonatal urinary ascites due to obstructive uropathy.

PURPOSE: Neonatal urinary ascites is a rare complication of obstructive uropathy with possible lethal outcome if not treated adequately. We demonstrate that with adequate therapy the survival rate can be high and long-term survival, kidney function and lower urinary tract function of patients with urinary ascites can be good. MATERIALS AND METHODS: The study included 4 females and 8 males born with urinary ascites. Followup ranged from 3 to 14 years. Blood analysis for renal function, electrolytes and blood gas was performed at hospitalization and during followup. Ultrasound, cystourethrograms or cystoscopy showed the site of obstruction and leakage of urine. All patients were initially treated with drainage of the ascites and decompression of the obstructed urinary tract. All patients underwent surgery to remove the obstruction and reconstruct the urinary tract. Bladder and kidney function was evaluated at long-term followup. RESULTS: All patients had severe abdominal distention at presentation. Severe metabolic acidosis was present in cases that had not been detected prenatally or immediately after birth. Two patients died of causes related to pulmonary hypoplasia. Surprisingly urinary continence and renal function were good in 9 of 10 survivors. CONCLUSIONS: Long-term outcome of bladder and kidney function is surprisingly good in cases of severe obstructive uropathy with ascites. Intrauterine pressure relief of the bladder through urinary extravasation protects renal function and this decompression of the urinary tract prevents severe secondary changes to bladder function. Although not proven we believe that high intrauterine pressures in the abdominal cavity are prevented by peritoneal absorption of the extravasated urine and consequent dialysis through the placenta.

[Neonatal ascites: meconium ileus with perforation in mucoviscidosis]. / Neonataler Aszites: Mekoniumileus mit Perforation bei Mukoviszidose.

Many conditions are known associated with neonatal ascites such as cardiac and vascular malformations, as well as malformations of the brain, kidney, lung and bone, chromosomal abnormalities, infections, fetal anemias, tumors, metabolic and maternal conditions. In 30% no reason can be found. Meconium ileus is a causal gastrointestinal abnormality. We report about a preterm infant 35 weeks of gestation with complicated meconium ileus because of mucoviscidosis.

Presacral teratoma presenting with congenital urinary ascites.

Congenital teratomas occur most frequently in the sacrococcygeal region. Most grown into a large perineo-sacral swelling that is conspicuous externally. Infrequently, the neoplasm is contained almost entirely within the pelvis in the presacral space. Congenital urinary ascites is observed in patients with obstructive uropathy; posterior urethral valves in a newborn is one of the most prominent causes of urinary ascites. We report a case of presacral teratoma leading to rupture of the urinary bladder due to outflow obstruction and causing urinary ascites. The ascites was drained, the bladder was repaired, and the teratoma was successfully excised. A review of the literature did not reveal any similar case.

Ruptured cystic mesenchymal hamartoma: an unusual cause of neonatal ascites.

Cystic mesenchymal hamartoma is an uncommon benign liver neoplasm usually seen in infants with an asymptomatic abdominal mass [1]. We report a neonate who presented with a ruptured cystic mesenchymal hamartoma which produced respiratory distress due to massive ascites. To our knowledge, this complication has never been reported.

Necropsy findings in a fetus with a 46,XY,dic t(X;21)(p11.1;p11.1).

We report the findings in a fetus terminated because of multiple abnormalities diagnosed on ultrasound, including asymmetry of the limbs, a hypoplastic diaphragm, unilateral duplex kidney with a double ureter, unilateral cystic kidney, and congenital heart disease including total pulmonary atresia. Cytogenetic studies showed an unbalanced translocation of the long arm of the X chromosome to chromosome 21, resulting in a 46,XY,dic t(X;21)(p11.1;p11.1) karyotype. The cytogenetics were confirmed by non-isotopic in situ hybridisation using probes specific to pericentric alphoid repeats. Parental chromosomes were normal indicating this to be a de novo translocation. It is suggested that the inactivation of the long arm of the X chromosome has resulted in an effective monosomy for chromosome 21.

[Bilateral kidney dysplasia with ascites in premature newborn infant]. / Displasia renale bilaterale con ascite in neonato prematuro.

The case refers to a premature newborn with anhydramnios and related foot malformations, renal dysplasia (Potter II-IV) and marked ascites. Hypoplasia of one umbilical cord artery was also found. Renal dysplasia according to Potter classification was difficult to be assessed being a borderline case between grade II and IV. The mother underwent methimazole and oestroprogestin treatment in the first period of pregnancy.

[Cystic hygroma of the neck and non-immunologic hydrops fetalis]. / Zystisches Nackenhygrom und nicht-immunologischer Hydrops Fetalis.

Fetal cystic hygromas are a manifestation of early lymphatic obstruction. They are mostly associated with nonimmune hydrops fetalis. They often occur in a number of chromosome abnormalities (Turner syndrome and Down syndrome). We report on a prenatally detected case with nuchal cystic hygroma and nonimmune hydrops fetalis without chromosome aberration and without further major malformations. Postnatally hygroma and hydrops regressed.

Hydrothorax, ascites, and right diaphragmatic hernia.

Hydrothorax and/or ascites may be the most striking finding in children with right diaphragmatic hernia. The clinical, radiographic, and pathologic findings of five children with right diaphragmatic defects through which the liver had herniated are described. Three presented with a right hydrothorax, one with a right hydrothorax and ascites, and another with ascites. All four children with large right hydrothoraxes were found to have an incarcerated peritoneal sac filled with fluid in the right side of the chest at surgery or autopsy. Lymphatic congestion and obstruction was the probable cause for the fluid collection, which tended to enlarge with time. This condition may be life threatening, and two of the four patients died soon after birth because of hypoplasia of the lungs. Fetal ultrasonography in both had disclosed right intrathoracic cystic masses, and in one, intrauterine aspiration to decompress the lungs had been attempted. The other two patients are alive and well following surgical repair at 1 week and 7 months of age. Ascites was present in two patients and was believed to be due to hepatic venous obstruction, a mechanism similar to that responsible for the Budd-Chiari syndrome.

alpha 1-antitrypsin deficiency presenting with ascites and cirrhosis in the neonatal period.

We report a 2-wk-old baby with alpha 1-antitrypsin deficiency of Pizz phenotype, who presented with massive ascites and hepatomegaly. Liver biopsy disclosed active established cirrhosis. Unlike all other reported newborns with Pizz type, the patient had no evidence of neonatal cholestatic jaundice. The presentation of Pizz with established liver cirrhosis at such an early age not only adds another cause of cryptogenic cirrhosis in the neonatal period, but also points to a liver insult in some patients with Pizz, which is already determined in utero.