Mapping of the gene for autosomal recessive polycystic kidney disease (ARPKD) to chromosome 6p21-cen.

Autosomal recessive polycystic kidney disease (ARPKD) is one of the major hereditary nephropathies in children predominantly presenting in early childhood. The clinical picture is variable but there is a fatal outcome in many cases. We have performed linkage analysis in 16 ARPKD families and localized the ARPKD gene to chromosomal region 6p21-cen with no evidence for genetic heterogeneity among different clinical phenotypes. Linkage was confirmed using six adjacent microsatellite markers and the highest lod score of 7.42 was obtained with D6S272 at theta = 0.00. Our findings should lead to more accurate forms of prenatal diagnosis than those currently available using ultrasound.

Munchausen by proxy or Polle syndrome: which term is correct?

The terms Munchausen syndrome by proxy and Polle syndrome have both been used to describe the situation in which one person persistently fabricates illness on behalf of another (usually a mother on behalf of her child). However, investigation of the family records of the real life Baron von Munchausen in Germany reveal that Polle syndrome is an inappropriate title originally derived from incorrect information.

The value of conjunctival biopsy in childhood cystinosis.

Cystinosis is frequently presented with cystine storage in the cornea and conjunctiva, and the diagnosis can be established by slit-lamp examination. It can also be confirmed by electron microscopy of a conjunctival biopsy. The present paper reports on a 16-month-old boy with Fanconi's syndrome, in whom the slit-lamp examination did not show crystal deposits of cystine in the conjunctiva. The ultrastructural study of the conjunctival biopsy demonstrated polygonal crystals within double membrane-limited organelles located in fibroblasts. Similar crystals were subsequently found in a kidney biopsy. We therefore think that conjunctival biopsy is a valuable diagnostic tool prior to performing renal biopsy, even in cases with negative findings by ophthalmologic examination.

[Psychosocial care for children with chronic renal failure (author's transl)]. / Psychosoziale Betreuung des chronisch nierenkranken Kindes.

After dialysis and kidney transplantation have become widely accepted methods to ensure the survival of uremic children, adequate psychosocial care for those affected becomes more and more important. Problems like parental overprotection, sibling rivalry, low school attendance rates, non-compliance with medical measures, social and economical stress in the family can only be overcome by the combined efforts of a specialized team. Comprehensive medical information, psychological support for individuals and groups, continuous critical evaluation of all medical measures, parents' groups and organized holiday activities for uremic, dialyzed and transplanted children have proved to be helpful methods.

Kidneys on vacation: the notion of renal work and the introduction of nonpharmacological therapies.

"Wisdoms of today become the follies of tomorrow," remarked none other than Franz Volhard, who first classified renal disease. In earlier times, nephrologists relied less on controlled randomized prospective trials and more on common sense. One such notion was the idea that kidneys could be "rested" by requiring them to make less urine. Particularly in Germany early in this century, patients with chronic renal disease were advised to go to Assuan in Egypt, where the warm sunny weather and low humidity decreased their urinary output. Thus, a "vacation" was prescribed for sick kidneys, and indeed, early in his career Volhard also supported this notion. In a small but excellent study, Loewy, Wohlgemuth, Bickel, and Schweitzer concluded that a decreased urinary output, rather than decreasing renal work, would require a considerable increase in concentration of excreted solutes, a task that patients with renal insufficiency would not be likely able to meet. These findings, as well as the observation that renal patients often failed to return from Egypt, caused Volhard to change his mind.

Prenatal diagnosis of diffuse mesangial glomerulosclerosis by ultrasonography: a longitudinal study of a case in an affected family.

The 4th child of an Arabian consanguineous family with 2 previous infant deaths due to diffuse mesangial glomerulosclerosis (at the ages of 1 and 44 days) and 1 healthy 3-year old child was followed up by ultrasonography from the 9th until the 35th week of gestation. Ultrasound showed enlarged hyperechogenic kidneys from the 14th week onwards, and the amniotic fluid level was increased to the upper normal limit. An amniocentesis at 14+ weeks of gestation showed a normal male karyotype and normal alpha-fetoprotein levels in amniotic fluid and maternal serum. Albumin and alpha 1-microglobulin levels in the amniotic fluid were within the normal range and not useful for diagnostic purposes. The child was born at the 36th week of gestation and died of renal failure 21 days later. A postmortem renal biopsy specimen revealed diffuse mesangial glomerulosclerosis.

[Summer holiday camp for children with chronic renal disease (author's transl)]. / Fortbildung und Praxis Ubersichten

A summer camp was organized for 31 children with chronic renal disease. One third of the patients suffered from renal insufficiency. The medical and paedagogical problems which evolved during the stay could be solved satisfactorily under relatively simple external conditions. The camp offered opportunity for the detection of hidden psychosocial and behavioral problems induced by the disease. These could be treated appropriately. The most important prerequisite for the organization of summer camps of this kind is a well-trained and coordinated team which should include a paediatric nephrologist, psychologists, teachers, dieticians and social workers.

[Intoxication after use of salt as an emetic (author's transl)]. / Intoxikation nach Gabe von Kochsalz als Emetikum

Salt is generally contraindicated as an emetic in toxicological emergency situations. It can only be recommended when its rapid disappearance from the stomach can be guaranteed in the case of lack of vomiting. Less than 1 g salt per kg body weight may be lethal. The danger of sodium chloride becomes apparent from two severe cases of intoxication in children one of which was fatal. One of the two children was given salt as an emetic.

Nephronophthisis (medullary cystic disease of the kidney). A study using electron microscopy, immunofluorescence, and a review of the morphological findings.

Light and electron microscopic as well as immunofluorescent findings in kidney biopsies of 9 patients suffering from nephronophthisis are reported. The lightmicroscopic picture is unspecific except the cysts at the cortico-medullary junction which are present in 70% of cases. The immunofluorescent findings are either negative or unspecifically positive. On electron microscopy, the tubular basement membranes exhibit characteristic but not specific changes, i.e. homogeneous thickening, splitting, reticulation, thinning, complete loss, granular disintegration and collapse. These findings suggest that the "Anlageschwäche" of the nephron especially of the tubular basement membrane may be the primary lesion in nephronophthisis.

Diffuse mesangial sclerosis: association with unreported congenital anomalies and placental enlargement.

A case of diffuse mesangial sclerosis (DMS) associated with a number of undescribed congenital anomalies is reported. The occurrence of additional anomalies, especially ocular anomalies, is a common finding in DMS. However, neither megalocornea, Dandy-Walker malformation, postaxial hexadactyly, rocker-bottom feet, nor atrial septal defect, as observed in our patient, has been reported previously in association with DMS. This case might be considered an atypical manifestation of the Galloway-Mowat syndrome. In contrast to most cases of DMS, the patient revealed intrauterine proteinuria as the placenta was enlarged to 31% of birth weight. This case demonstrates that the large placenta, >25% of birth weight, is not only pathognomonic of the congenital nephrotic syndrome of the Finnish type but can also occur in DMS.

Autosomal recessive and dominant forms of polycystic kidney disease are not allelic.

Linkage analysis has been carried out in 11 kindreds with autosomal recessive polycystic kidney disease (ARPKD) using the genetic marker 3'HVR, closely linked (theta = 0.05) to the gene of the autosomal dominant type. Close linkage (theta less than or equal to 0.20) between the locus of the marker and that of ARPKD can be excluded. These data strongly suggest that the loci for the autosomal recessive and dominant forms of polycystic kidney disease are not allelic.

Fulminant metastatic calcinosis with cutaneous necrosis in a child with end-stage renal disease and tertiary hyperparathyroidism.

Metastatic calcinosis is a common feature of chronic renal failure. Its first manifestations are bone demineralization and non-visceral and/or visceral calcification with mostly mural deposits in arteries and arterioles. It is initially characterized by hyperphosphataemia followed by secondary or tertiary hyperparathyroidism. Cutaneous involvement is a rare complication. Histologically, the lesions show vascular calcification with ischaemic skin necrosis. Extreme cases may produce calcinosis cutis (calciphylaxis), i.e. disseminated calcification of the subcutaneous tissue and dermis in the form of hard painful cutaneous nodules and plaques with subsequent ulceration. Metastatic calcinosis is a disease affecting adults, while the dystrophic or idiopathic type can develop in children. We present the case of a 6-year-old boy with end-stage renal disease, attributed to congenital renal hypoplasia, and accompanied by secondary hyperparathyroidism. He developed fulminant tertiary hyperparathyroidism and metastatic calcinosis of the lungs, as well as cutaneous necrosis of the buttocks and legs, subsequent to calcification of arteries and arterioles. A maternal renal transplant failed to function. The serum parathormone, calcium and phosphate levels could not be controlled by maintenance dialysis, phosphate binders and calcitriol. Total parathyroidectomy without autotransplantation of parathyroid tissue rapidly returned the serum parathormone, calcium and phosphate levels to normal. In addition, topical treatment using merbromine solution and hydrocolloid dressings, healed the ulcers with significant scar formation, within 2.5 months after parathyroidectomy. A renewed increase of the calcium x phosphate product, 2 months after parathyroidectomy, was attributed to mobilization of calcium compounds from the viscera, as confirmed by a chest X-ray.

Bilateral Wilms tumor in a boy with severe hypospadias and cryptochidism due to a heterozygous mutation in the WT1 gene.

Mutations in the WT1 gene causing Wilms tumors were first reported in WAGR syndrome (Wilms tumor, Aniridia, Genitourinary malformation, mental Retardation) and Denys Drash syndrome (pseudohermaphroditism, Wilms tumor, nephropathy), but only in a few patients with hypospadias and cryptorchidism without other signs of Denys Drash (DDS) or WAGR syndrome WT1 mutations were identified. We report a boy, who was born in 1989 with hypospadias and bilateral cryptorchidism. Previous karyotyping and endocrine studies had ruled out any known cause of male pseudohermaphroditism. Subsequently, he developed a bilateral Wilms tumor, which was detected by palpation at the age of 15 months during a routine visit by the general pediatrician. Because of its extensive size, surgery and chemotherapy were needed for treatment. Analysis of the WT1 gene was performed 5 y after diagnosis and revealed a C to T transition in one allele generating a stop codon at codon 362 and subsequently leading to a truncated protein with loss of its ability to bind to DNA. No signs of DDS or WAGR syndrome are present in the boy. The work up of this patient and the so far known few comparable cases from the literature lead to the conclusion that in newborns with severe urogenital malformations not due to known chromosomal or endocrine disorders mutational screening of the WT1 gene should be performed, to evaluate the high risk of developing a Wilms tumor. We favor mutational screening in these patients as an easy tool for investigation, because in the future it will probably decrease the necessity of frequent control visits in patients without a WT1 mutation.