Alagille's syndrome associated with cystic renal disease.

Although renal abnormalities have been described in children with Alagille''s syndrome, cystic kidney disease has not often been documented, and then usually only at necropsy. Three children with Alagille''s syndrome are described, in two of whom a unilateral multicystic dysplastic kidney was detected by prenatal ultrasound; in the other, a solitary cortical cyst was found later in childhood. All have normal renal function, growth, and liver synthetic function but continue to have clinical and biochemical signs of cholestasis. These cases show that unilateral cystic kidney disease with or without renal dysplasia may be associated with Alagille''s syndrome, that the clinical course is not necessarily unfavourable, and that Alagille''s syndrome should be included in the differential diagnosis of cystic kidney disorders associated with cholestatic liver disease. Patients with Alagille''s syndrome should be evaluated by renal ultrasound.     

Multiple unilateral renal cysts in two children

We report two children who presented with multiple renal cysts involving only one kidney and in whom there was no family history of renal disease and who did not have syndromes known to be associated with renal cystic disease. This unilateral involvement may represent a distinct entity, which has only been previously described in three cases; however, long-term follow-up will be needed to confirm this hypothesis. We illustrate the sonographic and computed tomographic findings, and the differential diagnosis is discussed. Received: 24 May 1999 Accepted: 22 December 1999     

Neonatal hepatitis syndrome with paucity of interlobular bile ducts in cystic fibrosis.

A male infant presenting with neonatal hepatitis syndrome, characterized by conjugated hyperbilirubinemia and very mild liver function test abnormalities, at 2 weeks of age was found to have no excretion of radioisotope into the intestinal tract on hepatobiliary scan. Liver biopsy revealed severe interlobular bile duct paucity. Other features of Alagille's syndrome were not present; other conditions frequently associated with interlobular bile duct paucity were also excluded. Subsequently, the infant was found to have cystic fibrosis. Cystic fibrosis is thus another disease that may be associated with paucity of interlobular bile ducts presenting as neonatal hepatitis syndrome, and this represents a different pathogenesis of cholestatic jaundice in neonates with cystic fibrosis besides those previously recognized.     

Renal histopathology in Alagille's syndrome

Various renal abnormalities have been reported in Alagille's syndrome (arteriohepatic dysplasia), usually as single case reports. The renal findings at autopsy of four patients with Alagille's syndrome, ranging in age from 4 1/2 months to 7 years, 2 of whom had evidence of renal dysfunction, are described and are compared with kidneys from patients with other cholestatic liver diseases of childhood. Two of the Alagille's patients had histologic findings suggestive of membranous nephropathy and special stains revealed accumulation of lipid in the glomerular and tubular basement membranes. Immunofluorescence of 1 revealed extensive accumulation of IgG and IgM. One patient had medullary cysts and mild interstitial fibrosis, and the fourth had a large subcapsular cyst and mild tubulointerstitial nephritis. All 4 cases, when examined with the electron microscope, revealed varying degrees of basement membrane thickening, splitting, and vacuolation with dense osmiophilic particles, most prominent in the patients with membranous nephropathy. These ultrastructural findings did not correlate with the degree of hyperlipidemia, but rather with the patient's age, and were also observed in other cholestatic diseases. The findings suggest that Alagille's syndrome is frequently associated with renal abnormalities, including lipid deposition, which may in some instances, lead to clinically significant renal impairment.     

Isolated unilateral tuberous sclerosis-associated renal cystic disease in a neonate

We present a male infant with antenatally detected, focal, unilateral apparently isolated renal cystic disease with morphological features of renal involvement in tuberous sclerosis. Only one previous case with similar presentation has been described. Most affected children present with either diffuse bilateral renal cystic disease or extrarenal manifestations. The major genes involved in tuberous sclerosis are now well described, and early onset of severe renal cystic disease in affected children often is related to the presence of a contiguous gene deletion syndrome involving TSC2 and PKD1 on chromosome 16.     

ISOLATED UNILATERAL TUBEROUS SCLEROSIS-ASSOCIATED RENAL CYSTIC DISEASE IN A NEONATE

We present a male infant with antenatally detected, focal, unilateral apparently isolated renal cystic disease with morphological features of renal involvement in tuberous sclerosis. Only one previous case with similar presentation has been described. Most affected children present with either diffuse bilateral renal cystic disease or extrarenal manifestations. The major genes involved in tuberous sclerosis are now well described, and early onset of severe renal cystic disease in affected children often is related to the presence of a contiguous gene deletion syndrome involving TSC2 and PKD1 on chromosome 16.     

儿童肾囊性疾病的诊治

Potter分型将儿童肾囊性疾病分为4型:常染色体隐性遗传性多囊性肾病、多囊性肾发育不良、常染色体显性遗传性多囊性肾病、梗阻性囊性发育不良肾.此外,单纯性肾囊肿、发生在肾肿瘤及其他伴囊性肾病的综合征也可引起肾脏呈囊性改变.这类病由于其发病机制和病理基础不同,临床诊断及治疗方案选择亦不同,要正确诊断这类疾病,需要仔细分类并查明病因.该文就儿童常见的肾囊性疾病进行综述.     

Fetal and infantile hypertension caused by unilateral renal arterial disease.

Three children who presented with heart failure in infancy caused by severe hypertension as a result of unilateral renal arterial disease are described. One presented at 3 days of age with persistent fetal circulation and heart failure. He had abnormal great vessels that indicated that the hypertension was of long standing and therefore fetal; this has not been described previously. The other two children failed to thrive because of unrecognised hypertension and subsequently presented with heart failure. All three underwent unilateral nephrectomy which cured their hypertension, and all were thriving at the time of writing. The benefits of nephrectomy outweighed the operative risks and loss of renal function. Blood pressure should be measured in children who are failing to thrive as part of routine clinical practice.     

Renal cysts associated with Turner's syndrome

After noting several occurrences of cystic kidney disease in Turner's syndrome we retrospectively reviewed the renal sonograms of 12 patients with this syndrome. Single renal cysts occurred in two patients and a multicystic dysplastic kidney in another. Our experience suggests that single renal cysts are a relatively frequent finding in Turner's syndrome and should be recognized within the scope of renal abnormalities associated with it.     

Cutaneous lesions in the orofaciodigital syndrome]

The term OFD syndrome designates a group of heterogeneous clinical patterns of which seven different types have been described. Type I, or Papillon Léage syndrome, is the most common pattern and the only type in which skin lesions occur. Type I OFD is a sex-linked dominant disorder. Two cases of OFD Type I with cystic lesions of the face are reported herein. The second patient also had polycystic kidneys. This combination has already been reported previously and all children with OFD should be investigated for polycystic kidney disease.     

Hepatocellular carcinoma in Alagille's syndrome: a family study

Alagille's syndrome is a common form of familial intrahepatic cholestasis. In addition to the hepatobiliary system, many other organ systems are affected. Most of the affected patients survive through adulthood. Hepatic involvement is the cause of death in about one-third of patients. Hepatocellular carcinoma complicating the course of this disease is very rare and has been reported previously in only three cases. We report a family in which three of four siblings with this syndrome developed hepatocellular carcinoma and died as a result of it. None of these children had a liver disease, other than Alagille's syndrome, that could account for the development of such a tumor. This experience suggests that Alagille's syndrome, or at least chronic cholestasis, may be a predisposing factor for the development of hepatocellular carcinoma. Annual determination of alpha-fetoprotein and abdominal computed tomography (CT) scan may detect the development of a hepatocellular carcinoma in such cases while they are still resectable.     

LYMPHANGIOMA OF THE RIGHT KIDNEY IN AN INFANT BOY

A 9-month-old boy with a primary cystic lymphangioma of the right kidney is reported. The clinical and radiological features favored a malignant tumor. Histology revealed the lesion to be a lymphangioma; the diagnosis was confirmed by immunohistochemistry and chemical analysis of the intracystic fluid. Lymphangiomas of the kidney are rare in adults; they are even rarer in infants and children. Nevertheless, renal lymphangiomas should be considered in the differential diagnosis of multicystic, unilateral renal masses, independent of the age of the patient.     

Ultrasonographic features of glomerulocystic disease in infancy: similarity to infantile polycystic kidney disease

Glomerulocystic kidney disease (GCD) is an unusual condition characterized pathologically by cystic dilatation of Bowman's space and the first portion of the proximal convoluted tubule. We report the serial ultrasound findings in an asymptomatic infant with GCD which were initially confused with infantile polycystic kidney disease. We emphasize the nonspecificity of ultrasonographic findings in cystic renal disease in early infancy and suggest a protocol for the diagnostic work-up of bilateral renal cystic disease in children.     

Polycystic kidney disease and other genetic kidney disorders

Cystic kidney diseases encompass a range of genetic disorders in which the primary cilia of the cells are affected and thereby cysts form as a result. There are an increasing range of cystic renal diseases recognized due to the advances in genomics. The most common genetic kidney condition is autosomal dominant polycystic kidney disease (ADPKD). ADPKD leads to renal failure in adulthood. In children, hypertension is common and if treated, may slow down renal decline. The most common cystic kidney disease causing renal failure in children is autosomal recessive polycystic kidney disease (ARPKD). ARPKD also affects the liver. These conditions often have extra-renal features which also need to be addressed. Until recently, treatments were mainly supportive but now it is possible to slow down development of cyst formation and renal decline in ADPKD. This raises hope for treatment for other cystic renal conditions as more genes are identified and underlying mechanisms defined.     

A spectrum of segmental multicystic renal dysplasia

Background. Multicystic renal dysplasia (MCDK) is a common anomaly well described in the literature, but less well described when involving only a portion of a kidney. Objective. To present the imaging spectrum, natural history and associated anomalies of six kidneys with segmental MCDK. Materials and methods. Five children with segmental MCDK (one with bilateral segmental MCDK) referred to our hospital between 1989 and 1996 were reviewed. All had at least one ultrasound examination. Four had a voiding cystogram and three had renal scintigraphy. Results. Four children had antenatal diagnosis of cystic renal abnormality. In two, with obvious duplex kidneys and associated ureteroceles, the diagnosis of upper moiety MCDK was obvious either antenatally or immediately postnatally. In the other three there were diagnostic difficulties. One patient had bilateral widespread cysts obscuring the functioning renal portions. Another presented in utero with a large ureterocele and a cystic upper pole that had involuted by birth. The fifth had a nephrectomy at 3 years for a multiloculated cystic mass. Varying degrees of involution occurred in the five kidneys seen early. Reflux was demonstrated into the ipsilateral functioning lower moiety and midpole. Conclusion. In these children as in other studies, the commonest presentation of segmental MCDK is in the upper pole of a duplex kidney associated with a ureterocele at the end of the atretic ureter. Atypical segmental MCDK may present a diagnostic dilemma and should be included in the differential diagnosis of multiloculated cystic masses and cystic kidneys. Received: 16 June 1998 Accepted: 16 November 1998     

Cystic renal involvement in tuberous sclerosis

We describe two cases of unusual presentation of tuberous sclerosis with cystic renal involvement. A 19-month-old white male who was initially misdiagnosed as having polycystic kidney disease of "adult-type" developed petit mal seizures and small "ash-leaf" depigmented areas, raising a suspicion of tuberous sclerosis. Computerized tomography (CT) of the brain revealed periventricular calcifications, confirming the diagnosis of tuberous sclerosis. A 15 3/4-year-old black female with tuberous sclerosis showed acceleration of renal failure. Computerized tomography scan of the abdomen showed cystic lesions of the kidneys. In young children with cystic renal involvement but a negative family history of tuberous sclerosis or polycystic kidney disease, a CT scan of the brain should assist in the diagnosis. A CT scan or ultrasound examination of the abdomen will differentiate cystic renal lesions from angiomyolipoma of the kidneys.     

氯离子通道与肾脏病

氯离子是生物体内一类重要的阴离子,参与多种生理活动的调节。由相关基因突变引起的离子通道蛋白功能缺陷可导致离子通道功能异常,形成离子通道病。在肾脏,位于不同部位的肾小管上皮细胞的基侧质膜和顶质膜上分布有多种氯离子通道。研究发现,肾脏电压门控氯离子通道与Bartter综合征和Dent病有关;囊性纤维化跨膜转运调节体所致囊性纤维化病可累及肾脏。文章综述氯离子通道在维持正常肾脏功能中的作用及其机制,以及相关基因缺陷所致的肾脏疾病。     

Percutaneous nephrostogram in the newborn with bilateral renal cystic disease

Percutaneous antegrade pyelography should be considered in the few, select, critically ill newborns with bilateral renal cystic disease when the diagnosis is critical to management and difficult with the usual imaging procedures. Two extremely ill newborns with severe oliguria and cystic abnormalities in both kidneys by ultrasound underwent sonographic guidance for percutaneous antegrade nephrostograms in the first week of life. With injection of contrast medium, definitive diagnoses were made of a multicystic dysplastic kidney on one side and an obstructed hydronephrotic kidney on the other, thereby directing decompression of the obstructed kidney to preserve native renal function. This procedure can provide a definitive diagnosis in these rare but difficult cases.     

Pediatric patient with end‐stage kidney disease secondary to Eagle‐Barrett syndrome and metastatic unresectable hepatoblastoma treated successfully with chemotherapy and liver‐kidney transplant

HBL is the most common malignant liver neoplasm in children. The etiology of HBL is largely unknown but there are certain syndromes, such as Beckwith‐Wiedemann syndrome, that have been clearly associated with an increased incidence of this malignancy. EBS, also known as prune belly syndrome, is a congenital anomaly characterized by lax abdominal musculature, bilateral cryptorchidism requiring, in some cases, hemodialysis due to significant kidney and urinary tract dysfunctions. Despite an improvement on the survival rates of patients with advanced‐stage HBL, the presence of concomitant end‐stage renal disease that occurs in patients with EBS constitutes a therapeutic challenge for the clinician not only due to the use of nephrotoxic chemotherapy but also due to the potential need for multi‐organ transplant. We report case of a 2‐year‐old male patient with EBS diagnosed with stage IV, metastatic HBL successfully treated with multi‐agent chemotherapy while on dialysis whom then underwent a simultaneous liver‐kidney transplant followed by adjuvant chemotherapy. Ultimately, the patient achieved cancer remission with normalization of his renal function. Our report emphasizes that patients with HBL in the setting of EBS will not only require careful kidney function monitoring while receiving chemotherapy, but they might also need to undergo multi‐organ transplantation in order to achieve adequate cancer control and also normalization of their kidney function. Awareness of this unusual association calls for further investigation to potentially establish a genetic association between these two disease processes.     

Pediatric liver transplantation for fibropolycystic liver disease

Fibropolycystic liver disease includes CHF, Caroli's syndrome, and Caroli's disease. Patients with Caroli's disease and Caroli's syndrome have an increased risk of recurrent cholangitis, intrahepatic calculi, biliary cirrhosis, and cholangiocarcinoma. The aim of this study was to examine the post-transplantation outcomes of children with fibropolycystic liver disease. Of the 158 children transplanted at Seoul National University Hospital, there were four patients with Caroli's syndrome, two patients with CHF, and one patient with Caroli's disease. One patient underwent combined liver/kidney transplantation. Associated renal manifestations included ARPKD in three children and nephronophthisis in one child. The indications for LT were recurrent cholangitis, decompensated cirrhosis, and refractory complications of portal hypertension. Both graft and patient survival rates were 100% at a median follow-up period of two yr after LT. Three children with growth failure achieved catch-up growth after LT. In three patients with ARPKD, mean serum creatinine levels increased from 0.53 mg/dL at the time of LT to 0.91 mg/dL at the last follow-up (p = 0.01). LT is an excellent option for children with complications from fibropolycystic liver disease. Renal function should be monitored cautiously after LT in the patients with ARPKD.