Association of congenital hepatic fibrosis with autosomal dominant polycystic kidney disease

The association of autosomal recessive polycystic kidney disease (ARPKD) with congential hepatic fibrosis (CHF) is well known; a rare occurrence is that of congenital hepatic fibrosis with autosomal dominant polycystic kidney disease (ADPKD). We report a family with ADPKD in which congenital hepatic fibrosis with severe portal hypertension (PHT) presented in a 4-year-old girl; the kidneys were initially normal. Typical changes of autosomal dominant polycystic kidney disease developed in the next decade and were also found in the mother and sister (neither of whom had any evidence of portal hypertension). Severe variceal bleeding was treated by sclerotherapy and beta receptor blocade.     

Unilateral abdominal mass: an unusual presentation of autosomal dominant polycystic kidney disease in children

Autosomal dominant polycystic kidney disease is rarely diagnosed in infancy or childhood. The renal involvement is typically bilateral. We describe two children with ADPKD (autosomal dominant polycystic kidney disease) presenting with a unilateral renal mass. The value of a careful genetic history and the role of sonography will be discussed.     

Renal cystic disease: new insights for the clinician

This article cannot comprehensively cover the enormous strides made in defining the molecular and cellular basis of renal cystic diseases over the last decade. Therefore, it provides a brief overview and categorization of inherited, developmental, and acquired renal cystic diseases, providing a relevant, up-to-date bibliography as well as a useful list of informative Internet Web sites. Its major focus is the translational biology of polycystic kidney disease. It demonstrates how emerging molecular and cellular knowledge of the pathophysiology of particular diseases such as autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ADPKD) can translate into innovative therapeutic insights.     

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.     

Novel association of familial testicular germ cell tumor and autosomal dominant polycystic kidney disease with PKD1 mutation

Adolescent brothers were diagnosed with testicular germ cell tumors within the same month. Both were found to have multiple renal cysts on pretreatment imaging done for staging. The proband, his brother, and their mother, were all found to have a novel splice variant in intron 8 of the PKD1 gene by clinical exome sequencing. This is the second family reported with both familial testicular germ cell tumor (FTGCT) and autosomal dominant polycystic kidney disease (ADPKD), and the first described association of FTGCT with a splice variant in PKD1. We suggest that this novel variant in PKD1 may convey increased risk for FTGCT in addition to causing ADPKD.     

Nephrocalcinosis in a child with autosomal dominant polycystic kidney disease and a prolapsing ectopic ureterocele

Although autosomal dominant polycystic kidney disease commonly presents in adults, it can occur in children. Usually, renal calcification in patients with autosomal dominant polycystic kidney disease is manifested as calculi or as hemorrhage into a renal cyst. An ectopic ureterocele is a well-known finding in patients with renal duplication. To our knowledge, this is the first case report of a child who had combined findings of autosomal dominant polycystic kidney disease, nephrocalcinosis, and an obstructing ectopic ureterocele.     

Syndrome d'Angelman et anévrisme intracrânien : association fortuite ou prédisposition génétique commune ?

Although the pathogenesis of cerebral aneurysms has been studied intensively, it is yet poorly understood. However, a genetic predisposition to this pathology has been often suspected. We describe a patient with both intracranial aneurysm and Angelman syndrome. Angelman syndrome is characterized by severe mental retardation, inappropriate laughter, absent speech, dysmorphic facial features and seizures. It is due to genetic abnormalities of chromosome 15. Cerebral aneurysms are sometimes associated with inherited diseases like autosomal dominant polycystic kidney disease. Moreover several candidate genes have been analysed, to search for genetic variants which might be associated with the occurence of intracranial aneurysms. Our question is: is the association described in our observation fortuitous or do these diseases share a same genetic predisposition? Our observation also supports the hypothesis of a genetic participation in the genesis of cerebral aneurysms.     

Does the tuberous sclerosis complex include intracranial aneurysms?

Background. Tuberous sclerosis is a protean, genetically determined disease that may involve any organ or tissue and lead to a great number of symptoms and clinical features. Objective. Diagnosis can be very difficult in cases with incomplete manifestations (formes fruste) lacking the classic signs of the disease. Materials and methods. We report a case fulfilling the diagnostic criteria for tuberous sclerosis (shagreen patches, hypomelanotic macules, renal cysts and angiomyolipomas, and “migration tracts” in the cerebral white matter) in association with a giant intracranial aneurysm, but lacking mental retardation, epilepsy and facial angiofibroma. Results. Fourteen other cases of tuberous sclerosis and intracranial aneurysms, all but one without any clear sign of polycystic kidney disease, were found in the literature. Conclusion. We suggest that vascular dysplasias in general and aneurysms (mainly intracranial) in particular can be added to the other non-primary diagnostic features for the clinical diagnosis of tuberous sclerosis. Received: 18 August 1997 Accepted: 15 June 1998     

Sonographically detectable cysts in polycystic kidney disease in newborn and young infants

Autosomal dominant (adult type) and autosomal recessive (infantile type) polycystic kidney disease are 2 distinct forms of hereditary cystic renal disease with differing pathologic and clinical features. Glomerulocystic kidney disease is probably a separate entity, whose pathologic features may closely resemble those of autosomal dominant polycystic kidney disease, especially in small infants. An example of each of these conditions in a small infant is presented, all of which had sonographically detectable cysts. Pathologic correlation was available in each case. While there are typical sonographic features of autosomal dominant and autosomal recessive polycystic kidney disease in newborn and young infants, there is no specific appearance of either condition, and glomerulocystic kidney disease can apparently resemble either one. Other investigations, particularly family studies and pathologic verification, are important in order to establish the correct diagnosis.     

Cystic kidneys in children

From 1976-1987 a total of 26 infants and children with polycystic kidney disease were treated at the Children's Hospital of the Medical School Hannover. 13 of them suffered from infantile recessive polycystic kidney disease (IRPKD), and 13 from adult dominant polycystic kidney disease (ADPKD). IRPKD was diagnosed at a median age of 0.33 years (range 1 day-13 years), ADPKD at 6.0 years (3 days-14 years). Of those with IRPKD two infants died from bacterial infection and two others developed terminal renal insufficiency at the age of 8 years, while the others are living and 1-20 years old. All those suffer from severe arterial hypertension and have reduced renal function, but only 5 developed signs of liver fibrosis. Of those with ADPKD one infant died from sepsis and renal insufficiency, while the others are well and now 2-17 years old. Only one child needs an antihypertensive treatment. The most important criteria to differentiate IRKPD and ADKPD in children are the genetic transmission, age of first manifestation, hypertension and renal function. The prognosis is much more severe in IRPKD than in ADPKD, but is not as infaust in IRPKD as often assumed.     

Autosomal dominant polycystic kidney disease in infancy

We report on a 6 months old infant with suddenly developed severe arterial hypertension caused by polycystic kidneys. Examinations of the relatives revealed similar changes of the kidneys in 4 adults and 5 children. They were all diagnosed to have autosomal dominant polycystic kidney disease. Excretory kidney function of all patients is normal; however, blood pressure was raised in the adults. We would like to stress the importance of family screening in this disease, in particular with regard to possible early diagnosis and treatment of arterial hypertension. The long-term prognosis of the early manifestation of the dominantly inherited cystic kidney disease is uncertain.     

Rare co-occurrence of osteogenesis imperfecta type I and autosomal dominant polycystic kidney disease

Background

There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease (ADPKD) and connective tissue disorders. A simultaneous occurrence of osteogenesis imperfecta (OI) type I and ADPKD has not been observed so far.

Methods

This report presents the first patient with OI type I and ADPKD.

Results

Mutational analysis of PKD1 and COL1A1 in the index patient revealed a heterozygous mutation in each of the two genes. Mutational analysis of the parents indicated the mother as a carrier of the PKD1 mutation and the father as a carrier of the COL1A1 mutation. The simultaneous occurrence of both disorders has an estimated frequency of 3.5:100 000 000.

Conclusion

In singular cases, ADPKD can occur in combination with other rare disorders, e.g. connective tissue disorders.

     

Body growth in children with polycystic kidney disease

We analysed the body growth of 121 prepubertal children with polycystic kidney disease participating in a longitudinal multicentre study. The patients were followed from an age of 1 to 9 years in girls and 1 to 10 years in boys over a mean period of 3.6 years. Children with end-stage renal disease were excluded. Fifty-four patients had the autosomal dominant form of the disease and 67 the autosomal recessive form. At last observation, 2% of patients with the dominant form and 28% of those with the recessive form had an estimated glomerular filtration rate of < 60 ml/(min 1.73 m²). At first observation, the mean height SD score (SDS) in patients with the dominant form was almost the same as in controls, whilst in those with the recessive form it was significantly decreased (girls –0.82 SDS, boys -0.68 SDS, p < 0.001). During the follow-up the height SDS decreased slightly in both groups (NS). In patients with autosomal recessive kidney disease the degree of growth retardation appeared to be related to renal function: at last observation the height of girls with an estimated glomerular filtration rate of < 60ml/(min 1.73 m²) was more retarded than that of boys (mean -2.1 SDS versus -1.5 SDS, NS). The height SDS and renal function at last observation correlated in girls ( r = 0.83, p < 0.001) but not in boys ( r = 0.55) with the recessive form. No correlation was found between the height SDS and hypertension. The weight-for-height SDS at onset was significantly reduced in patients with the recessive form with decreased renal function. Our data suggest that the autosomal recessive, but not the dominant, form of polycystic kidney disease is associated with early growth retardation, which seems to be more severe in girls, probably due to the more rapid deterioration of renal function.     

Colonic diverticulitis in young patients with chronic renal failure and transplantation

The association of colonic diverticulitis with chronic renal failure is well known. In those patients with adult autosomal dominant polycystic kidney disease, colonic diverticulitis is an especially common complication. We present two young patients (one teenager and one mid-twenties) who developed intra-abdominal abscess several years after renal transplantation. Neither patient had autosomal dominant polycystic disease nor a known history of gastrointestinal problems but both proved to have underlying, previously unsuspected colonic diverticular disease with abscess formation.     

MOLECULAR BIOLOGY OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Among the prevalent human genetic disorders, human autosomal dominant polycystic kidney disease is certainly one of the most challenging, both from a clinical and a fundamental perspective. In the recent years, important progress opened novel research avenues to elucidate the genetic basis, the cellular pathophysiologic mechanisms and the molecular function of genes and proteins involved in autosomal dominant polycystic kidney disease.     

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.     

Reduced methotrexate clearance and renal impairment in a boy with osteosarcoma and earlier undetected autosomal dominant polycystic kidney disease (ADPKD)

We report a 12-year-old boy with osteoblastic osteosarcoma of the right femur. He was started on chemotherapy according to the EURAMOS/COSS 1 protocol. Chemotherapy with doxorubicin/cisplatin resulted in reversible acute renal failure and methotrexate levels were repeatedly elevated. Family history suggested an autosomal dominant polycystic kidney disease. Genetic testing revealed a novel mutation c.10707_10712del (p.Val3569_3570del) in exon 36 of the PKD1 gene. Patients with autosomal dominant polycystic kidney disease may be at risk for acute renal failure during chemotherapy without signs of renal impairment. A careful family history is important to exclude risk factors for renal impairment before introducing high-dose chemotherapy.     

Blister-like supraclinoid internal carotid artery pseudoaneurysm in a 15-year-old male: case report and review of the literature

With an incidence of less than 1-3 per million, pediatric aneurysms are rare clinical entities. A traumatic etiology is implicated in a large proportion of these cases, leading to the formation of both 'false' and 'true' aneurysms. These occur most often in the distal circulation, but have also been described in the supraclinoid distal internal carotid artery (ICA). Blood blister aneurysms are also found in this location; however, they have not been described in the pediatric population. We report the case of a 15-year-old male who presented following cranial trauma with diffuse basal subarachnoid hemorrhage and limited additional intracranial pathology. Computed tomography angiography demonstrated a small, 2-mm blister-like aneurysm arising from the dorsal surface of the left supraclinoid ICA at a non-branching site. Despite early endovascular treatment with Guglielmi detachable coils, the lesion continued to grow over subsequent studies, necessitating open surgical clipping. At the time of surgery, gross pathology of the native ICA was observed, raising the possibility of a preexisting blood-blister aneurysm. We review the epidemiology, pathophysiology and diagnostic considerations of these lesions. The endovascular and surgical management of these complex non-branching supraclinoid ICA aneurysms is also discussed.     

Radiologic features of “adult type” polycystic kidney disease in the neonate

Two cases are reported of adult type polycystic renal disease (autosomal dominant) presenting in the newborn as a unilateral abdominal mass. The radiographic findings in the involved kidney simulated the ectatic tubules of infantile polycystic disease, yet histologic examination was consistent with the adult variety and both infants had other family members with adult type polycystic kidneys. These cases emphasize some of the ambiguities that exist in the definition and classification of polycystic renal disease.     

Choroby wątroby i nerek w przebiegu ciliopatii

Ciliopathies constitute a group of disorders characterized by cilia abnormalities and an extremely heterogeneous clinical presentation. The liver and kidneys are the most commonly affected organs and the term hepatorenal fibrocystic disorders is used to describe ciliopathies with combined liver and kidney involvement. Liver disorders in ciliopathies can be grouped into three categories: congenital hepatic fibrosis, Caroli's disease and polycystic liver disease. Kidney disorders related to primary cilia abnormalities include autosomal dominant and recessive polycystic kidney diseases and nephronophthisis.