Primary hemochromatosis in children: report of three newly diagnosed cases and review of the pediatric literature.

Hereditary hemochromatosis was diagnosed in three asymptomatic siblings following the unexpected finding of elevated serum iron concentrations. This diagnosis was confirmed by hepatic biopsy. Repeated phlebotomies resulted in a significant decline of serum iron and ferritin concentrations and a decrease of hepatic iron content. This report and a review of the literature indicate that the diagnosis of hereditary hemochromatosis must be considered more frequently in childhood. Organ dysfunction from iron overload may be minimized in children by the early commencement of regular phlebotomy.

Neuroblastoma in a child with Wiedemann-Beckwith syndrome.

We report on a patient with Wiedemann-Beckwith syndrome (WBS) who developed abdominal neuroblastoma. Although WBS patients are known to have a higher incidence of embryonal tumors, this is only the 4th known case of neuroblastoma associated with this syndrome. Chromosomes on peripheral lymphocytes and tumor cells were normal. Children with WBS should be screened for a variety of embryonal neoplasms, not only Wilms tumor.

Hepatocellular carcinoma in a child with familial Russell-Silver syndrome.

We describe a 4-year-old boy with Russell-Silver syndrome (RSS) found to have hepatocellular carcinoma. The brother of this child also had manifestations of RSS. This is the third malignancy and the first hepatocellular carcinoma described in a patient with RSS. The coexistence of hepatocellular carcinoma and RSS may be completely fortuitous; however, the known association of liver cancer with growth abnormality and hemihypertrophy, findings also present in RSS, suggest that these disorders may be related.

Juvenile galactosialidosis in a white male: a new variant.

We describe a 19-year-old white male with juvenile galactosialidosis. He presented with hip arthralgia and was found to have facial "coarseness," corneal clouding, mitral and aortic insufficiency, and hepatosplenomegaly. Ultrastructural studies of skin biopsy and peripheral blood lymphocytes showed membrane-bound inclusions containing sparse fibrillogranular material. Biochemical analysis showed elevated urinary sialyloligosaccharides and no free sialic acid. Fibroblast enzyme analysis showed low activities of both alpha-neuraminidase and beta-galactosidase. To date, most patients with juvenile galactosialidosis have been Japanese. However, unlike those patients, our patient did not have macular cherry-red spots, neurologic abnormalities, or mental retardation. We speculate that this young man represents a new subtype of juvenile galactosialidosis with a potentially different molecular defect from that of the Japanese variant.

Hepatic dysfunction in Alström disease.

Alström disease is a rare disorder; less than 20 cases have been reported. An 11-year-old girl is described with this condition. She has pigmentary retinopathy, sensory neural deafness, obesity, Type II diabetes mellitus, hyperlipidemia, and acanthosis nigricans. However, in addition she developed hepatic dysfunction, pathologically similar to chronic active hepatitis. This may be a further, previously undescribed systemic manifestation of Alström disease.

Neural differentiation in Wilms' tumor.

Immunoperoxidase studies using antibodies to neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), and S100 were used to confirm the presence of neural differentiation identified histologically in five cases of Wilms' Tumor. These observations invite reappraisal of Masson's proposed neuroectodermal histogenesis of Wilms' tumor because they are difficult to reconcile with the currently accepted metanephrogenic blastematous origin. They also provide a stimulus to examine the expression of neural markers during normal renal development and differentiation.

Severe perinatal liver disease and Down syndrome: an apparent relationship.

Down syndrome (DS) is not usually thought of in association with significant infantile liver disease. We present clinical and histopathologic data from 10 patients with DS who presented with severe liver disease at birth or within the first few weeks of life, and summarize the findings of eight previously reported cases. The liver disease was fatal in all but one case. Diffuse lobular fibrosis surrounding proliferating ductular elements and residual hepatocytes characterized the pathologic findings in the liver in all patients. A large number of megakaryocytes were present in the liver in nine of 12 patients. The phenotype of "perinatal hemochromatosis" was documented in eight of nine cases in which the presence of iron was investigated. Since only a fraction of the patients with this phenotype have DS, the patients we describe seem to represent a relatively well-defined subset of the perinatal hemochromatosis phenotype. The existence of such a subset suggests that the perinatal hemochromatosis phenotype does not represent a single etiopathogenetic disorder. The association between DS, megakaryocytic infiltrates in the liver, and fatal subacute/chronic liver disease gives rise to the speculation that fibrosis-promoting factors and/or metabolic abnormalities, such as those resulting from a gene dosage effect, may play a role in the genesis of the liver disease, perhaps due to a particular susceptibility of fetal liver.

Acute aluminum toxicity after continuous intravesical alum irrigation for hemorrhagic cystitis.

An encephalopathy and cardiomyopathy developed in a seventeen-year-old girl with chemotherapy-induced renal failure while receiving an intravesical aluminum infusion for hemorrhagic cystitis. Premortem serum and postmortem tissue aluminum levels were markedly elevated. It is likely that her inability to excrete absorbed aluminum contributed to her death. Aluminum infusions should be used with caution in patients with renal failure.

Congenital fibrosarcoma metastatic to the choroid.

A 2 1/2-year-old boy developed a choroidal metastasis from a congenital fibrosarcoma of the lower left limb that had been amputated shortly after birth. To our knowledge this is the first reported case of a congenital fibrosarcoma that metastasized to the choroid.

The high incidence of valproate hepatotoxicity in infants may relate to familial metabolic defects.

The incidence of fatal hepatic failure associated with valproic acid (VPA) therapy is highest in children under the age of three years, particularly in those with developmental delay. The pathogenesis of VPA hepatotoxicity is unclear but may relate to the accumulation of a toxic metabolite of VPA which impairs fatty-acid oxidation. We describe two unrelated infants with developmental delay who developed hepatic failure while receiving VPA. Siblings of both children subsequently developed hepatic steatosis and intractable seizures without being exposed to VPA. This suggests that the two children who developed liver failure when receiving VPA may have had a familial metabolic disorder. Familial metabolic disorders may account partly for the higher incidence of fatal hepatotoxicity described in infants receiving VPA.

Laboratory detection of metabolic disease.

This article describes the clinical signs, abnormal chemistry, histopathology, and biochemical tests that assist in the diagnosis of many inherited metabolic diseases. Small molecule diseases (for example, amino acid disorders, organic acidurias, and galactosemia) may present with acute illness and lead to unexplained death. Diagnosis of the specific enzyme defect may permit treatment by dietary changes or vitamin supplementation. Large molecule diseases are degenerative disorders due to storage of glycogen, glycoproteins, or mucopolysaccharides. Table 7 presents a compendium of laboratory investigations one should consider using when abnormalities are found in multiple organ systems. The investigation of a child with a mucopolysaccharidosis is used as an example of the use of this table. Investigating pediatricians should realize that many laboratory tests involved in the diagnosis of metabolic disease required special collection and handling by the laboratory.

Angiomyxoma of umbilical cord.

A rare angiomyxoma of umbilica cord occurred in a male infant. The presence of such a tumor with its vascular component arising from a hypoplastic umbilical artery supports the hypothesis that the lesions arose through improper placental vascularization.

Perianal rhabdomyosarcoma: report of a case in an infant.

Rhabdomyosarcoma is the most common childhood sarcoma, whereas, primary pararectal rhabdomyosarcoma is very rare. To date, four pediatric and eight adult cases have been reported. In children, the tumor presents as a perianal polypoid mass, often initially misdiagnosed. Formerly a very lethal sarcoma, rhabdomyosarcoma is now treated with combined surgery, radiation, and chemotherapy, with encouraging results.

Postoperative intussusception in a premature infant.

Intussusception occurs most commonly between the fifth and ninth month of life. Affected infants are usually healthy and born at full gestation age. We describe a case of intussusception occurring in a 10-day-old, 700-g neonate born at 28 weeks' gestation. The diagnosis was made at laparotomy 7 days after colostomy for imperforate anus. There were three associated bowel perforations. This case demonstrates that postoperative intussusception can occur in the premature infant. It also serves to illustrate the difficulty in making the diagnosis preoperatively.

Unique features of Helicobacter pylori disease in children.

In a six-year period, 41 children had endoscopically documented duodenal ulcer disease or primary H. pylori antral gastritis without duodenal ulcer. Of 37 children with H. pylori gastritis, group 1 comprised 23 patients with duodenal ulcer disease and group 2 had 14 patients without ulcers (primary H. pylori gastritis). Group 3 comprised four children with duodenal ulcer disease and H. pylori-negative antral biopsies. During the study period, all primary chronic ulcer disease was duodenal; no primary chronic gastric ulcer was present. Two distinct types of duodenal ulcer disease were identified; the majority (85%) was always associated with significant active H. pylori antral gastritis (group 1). The minority (15%) had virtually absent gastritis and no H. pylori (group 3). Native Indian children were represented in group 1 quite out of proportion to the referral population and had the most severe disease. While it is established that a higher prevalence of asymptomatic H. pylori infection exists in non-Caucasians, this appears to be the first demonstration of a higher prevalence of symptomatic ulcer disease in non-Caucasian children or adults. Caucasian children tended to have primary H. pylori gastritis (group 2) or duodenal ulcer without H. pylori (group 3). Antral nodularity was found to be an important specific endoscopic sign, unique to those children with H. pylori disease. It has not been described in adult H. pylori disease. Non-Caucasian children, especially Native Indians, in British Columbia have more prevalent and more severe H. pylori disease than Caucasians. Endoscopy with gastric antral biopsies is necessary to distinguish different types of duodenal ulcer disease and to diagnose primary H. pylori gastritis.

A model to begin reengineering the laboratory. How do you change an outmoded laboratory structure?

If a traditionally structured laboratory cannot incorporate new technologies efficiently and can no longer meet its changing service demands, it may require reengineering. A model is presented that can be followed by the laboratory director and a small group of planning colleagues to begin the process. The model was effectively used at British Columbia's Children's and Women's Hospitals (BCCH/WH) to review their laboratory structure and redraft it for the future. The model considers the external and internal pressures facing the laboratory. Technological trends, which have significant impact on laboratory service, are also incorporated into the model. The current list of services, staff expertise, and laboratory specialties is used as the base in the model to formulate the opportunities for improvements and identify the future direction of the laboratory. These opportunities are the context for the vision of the future laboratory. With this vision in mind and a creative planning approach, a new optimum laboratory structure can be outlined. This model begins the reengineering process and can be applied to any laboratory where there is the need for dramatic improvements to accommodate the changes in today's rapidly evolving health-care environment.

Strategies for a successful organizational transition. Identifying staff roles and fulfilling their needs during changing times.

For a successful reorganization of the laboratory, there is a role for each staff member to play during the transition. The role of those in laboratory administration is that of leading change agent. Corporate support staff, such as those in a human resources department, can advise the laboratory director in their areas of expertise. The role of the medical and technical supervisory staff is that of chief implementers of the plan. General laboratory staff has a confusing dual role--not only must they continue to provide laboratory services during the transition, but they also may have to change what they are doing and how they are doing it. Success also depends on meeting the individual personal needs of staff. Laboratory directors and administrators want to make a meaningful contribution to health care. Corporate support staff need to feel that they are a part of the change process. Supervisors' needs vary--coping with the loss of identity, position, or territory will be difficult for some; others will want to be involved in all stages of planning and implementation. The major need of the general laboratory staff is stability. Strategies are listed for each staff grouping to help the laboratory director coordinate staff roles and satisfy staff needs during the transition period.

Congenital multiple fibromatosis.

We present a case of congenital multiple fibromatosis to illustrate its characteristic clinical and histopathologic features. The importance of recognizing this disorder is emphasized because of its special clinical behavior and prognosis.

Cytomegalovirus infection of the bowel in infancy: pathogenetic and diagnostic significance.

Three infants had cytomegalovirus (CMV) infection of the bowel. Infected enteric ganglion cells were found in two, one of whom had hypoganglionosis and colonic dysmotility. The third infant had classic short segment Hirschsprung's disease and colitis with CMV inclusions in vascular endothelium, a situation wherein viral transformed cells may have led to misinterpretation of the diagnostic biopsy.

Endodermal variant of mature cystic teratoma of the ovary: report of a case.

The clinical and pathological features of a case of mature monodermal cystic teratoma of the ovary in a five-year-old girl are reported. The tumor was composed purely of respiratory epithelium. This appears to be the first report of such a case.