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Mutations in DAX-1 gene cause congenital adrenal hypoplasia (AHC). We present a male patient affected by X-linked adrenal hypoplasia congenita due to a novel DAX-1 missense mutation. The mutation V287G affects the C-terminal end of the DAX-1 protein which plays an important role in functioning of the receptor. In addition, our patient presented an inappropriate tall stature and renal ectopy, which have not been described in AHC so far., ((c) 2005 Wiley-Liss, Inc.)

Diabetes in childhood is the most common chronic disease and generally fits the type 1 category, even though other forms of non-autoimmune diabetes are now emerging in this age. At variance with adults, children and adolescents undergo physiological process, which may frequently require adjustments of clinical management of diabetes. Moreover, the hormonal and psychological changes during puberty may be crucial in conditioning management. Furthermore, common illnesses frequently affecting children may also destabilise metabolic control. Consequently, education in children is the cornerstone of treatment. This review focuses on the several and peculiar aspects of practical management of diabetes in paediatric age, which require professional figures such as paediatricians, nurses, dieticians, psychologists, social assistants originally trained in paediatric area, able to deal with the age-related medical, educational, nutritional and behavioural issues of diabetes.

The long-term sequelae on the growth pattern in successfully resected virilizing adrenal tumors (ACT) have not been clearly defined. We report on 10 years follow-up of a boy with virilizing ACT until the attainment of final height. This is the first clinical description in a boy with a marked advancement of bone age, indicating that despite advanced physical and skeletal maturity the prognosis on growth is good, provided that regression of virilization is obtained.

Severe Raynaud's phenomenon developed in a 5-year-old girl with chronic hepatitis C infection at the fifth month of interferon therapy in the absence of cryoglobulinemia and other conditions commonly associated with secondary Raynaud's phenomenon. Although interferon therapy was promptly discontinued, Raynaud's phenomenon persisted for 4 months with appearance of necrotic-ulcerous lesions at the tips of fingers.

Background: A complex interplay of malnutrition, intestinal dysfunction, and immune impairment increases the progression of human immunodeficiency virus (HIV) disease in children. The authors tested the hypothesis that nutritional support improves intestinal and immune functions in children infected with human immunodeficiency virus (HIV)., Methods: A questionnaire was circulated through reference centers for pediatric HIV infection to evaluate the effects of nutritional rehabilitation, total parenteral nutrition (TPN) and enteral nutrition (EN), in children. Information included changes in body weight, CD4 cell numbers, and intestinal absorption-as judged by the xylose load-before and after clinical nutritional support and the outcome of children., Results: Sixty-two children underwent nutritional support: 46 received TPN and 16 received EN. All but three had full-blown acquired immunodeficiency syndrome, and all were severely malnourished. Baseline clinical conditions were worse in children receiving TPN than in those receiving EN. Intestinal dysfunction was detected in all children who received xylose oral load. A significant increase in CD4 cell count, xylose levels, and body weight followed EN. A similar pattern was observed after TPN, but none of the parameters significantly changed. Twenty-seven children who received TPN and three who received EN eventually died. Fourteen who received TPN and eight who received EN were shifted to oral feeding, and five who received TPN and five who received EN continued with clinical nutritional support at the end of the observation period., Conclusions: Nutritional intervention may restore intestinal absorption and increase CD4 cell numbers. The efficacy of nutritional intervention is enhanced if provided before a terminal stage of HIV infection. These data provide evidence of a close association among nutritional condition, intestinal absorption, and immune impairment.

Adherence to antiretroviral therapy is a major problem in children with HIV infection, who depend on parents or foster parents for receiving drugs. During an ongoing investigation on intestinal function in children with symptomatic HIV infection who were treated with zidovudine, blood samples were obtained six hours after the administration of zidovudine as reported by the parents and, again, one and six hours after its administration in the hospital, and drug concentration was measured by radioimmunoassay. Both peak and steady state zidovudine levels were within the expected concentration ranges after administration in the hospital. In contrast, they were below the effective concentration in five of the 10 children that reportedly had received the drug at home by the parents. These data directly show poor compliance with antiretroviral therapy in children. Compliance with antiretroviral therapy should be carefully checked in children and strategies are needed to increase full and permanent adherence with antiretroviral therapy by people in charge to administer drugs to HIV-infected children.

Objectives: To investigate the intestinal absorptive processes in children with HIV infection before and after treatment with combination therapy that includes ritonavir. To test the hypothesis that combination therapy improves intestinal function., Design: Intestinal function tests were performed in 10 children with advanced HIV disease at the enrollment and after 3 and 6 months of therapy with ritonavir combined with two HIV reverse transcriptase inhibitors. HIV viral load and CD4 cell counts were also determined; body weight was monitored., Methods: The D-xylose absorption test, the steatocrit and the determination of fecal alpha1-antitrypsin concentration were used to evaluate carbohydrate and fat absorption, as well as fecal protein loss. Serum iron levels were measured to indirectly evaluate iron absorption. HIV-1 RNA-polymerase chain reaction (PCR) and immunofluorescence imaging were used to evaluate virologic and immunologic responses., Results: In all, 9 children had carbohydrate malabsorption, 3 steatorrhea, 2 protein loss, and 7 iron deficiency. Most tests produced normal results after 3 months of therapy, and all abnormalities were abolished 6 months after institution of combination therapy. Mean results of each of four absorption tests were significantly changed on combination therapy. Viral load was progressively reduced and CD4 count was increased, with an inverse relationship. An evident shift of body weight pattern toward catch-up growth was observed in all children., Conclusions: Ritonavir combination therapy results in prompt and sustained restoration of intestinal function, which is associated with reduction in viral load, increase in CD4 counts, and gain in body weight.

Background: The spectrum of severe and protracted diarrhea (SPD), previously defined as intractable diarrhea, has changed during the past several decades. Despite recent advances in determining the cause of SPD and in treatment, this syndrome still represents a challenge and is becoming a major problem affecting health care resources. This study was conducted to characterize the epidemiology, spectrum of causes, and the outcome of SPD in Italy in recent years., Methods: All the SPD cases seen at the major centers of pediatric gastroenterology in Italy during a 3-year period (1993-1996) were recruited in this multicenter, prospective survey., Results: Thirty-two children (26 boys and 6 girls; median age at the onset of SPD, 40 days) were enrolled in this study by 9 of 26 participating centers. Twelve were newly diagnosed cases, with an estimated SPD incidence rate in Italy of 0.64 to 0.92 x 10(-5) infants per year. The most common causes were autoimmune enteropathy (n = 8) and ultrastructural abnormalities of the enterocyte (n = 7), whereas food intolerance and postenteritis syndrome were less frequent (3 and 2 cases, respectively). Two children with autoimmune enteropathy fulfilled the criteria for the X-linked variant of this condition. At the end of the study period, 9 of 31 patients had recovered, 15 still had diarrhea, and 7 had died., Conclusions: Severe and protracted diarrhea is a rare but challenging problem in Italy. Because parenteral nutrition or intestinal transplantation are the only options in a subset of cases (e.g., ultrastructural abnormalities of the enterocyte), infants with SPD should be referred to specialized centers where advanced diagnostic and therapeutic facilities are available.

Background: Nutrient malabsorption frequently occurs in HIV infected children, but very few studies have investigated exocrine pancreatic digestive capacity in these cases., Aims: To investigate pancreatic function in HIV infected children and to determine whether faecal fat loss, a prominent feature of intestinal dysfunction, is associated with pancreatic dysfunction., Patients: Forty seven children with HIV infection without apparent pancreatic disease and 45 sex and age matched healthy controls., Methods: Pancreatic function was evaluated by measuring elastase 1 concentration and chymotrypsin activity in stools by ELISA and colorimetric methods, respectively. Intestinal function was evaluated by measuring fat and protein loss by the steatocrit method and by faecal alpha1 antitrypsin concentration., Results: 14 (30%) had abnormal pancreatic function tests: seven had isolated elastase activity deficiency, three isolated chymotrypsin deficiency, and four pancreatic deficiencies in both enzymes. Patient enzyme values were significantly lower than those of controls. Low faecal pancreatic enzymes were not associated with symptoms. Twelve children had steatorrhoea and four had increased alpha1 antitrypsin. Steatorrhoea was significantly associated with reduced faecal pancreatic enzymes. There was a significant negative correlation between elastase 1 concentration and steatocrit. Children with pathological faecal elastase 1 or chymotrypsin values did not differ from the other HIV infected children with respect to nutritional and immunological status, stage of HIV disease, presence of opportunistic infections, or drug administration., Conclusions: Abnormal pancreatic function tests are a frequent feature of paediatric HIV infection; this condition is associated with steatorrhoea, which probably contributes to the disease.

Background: Numerous studies have shown pancreatic disease in adult human immunodeficiency virus (HIV)-infected patients, but there are very few reports on pediatric patients. Our aim was to determine the prevalence of increased serum pancreatic enzyme levels and their relationship to clinical manifestations of acute pancreatitis in HIV-infected children., Methods: Forty-seven consecutive, symptomatic HIV-infected children (24 male; median age, 7.3 years; range, 1-17 years) and 45 sex- and age-matched controls without gastroenterologic disease were enrolled. In all subjects serum total amylase, pancreatic amylase, and lipase were assayed with commercial kits. The following were recorded: disease progression (CDC class), nutritional status (weight Z-score), CD4 lymphocyte count, drug treatment during the previous 12 months, presence of opportunistic infections, clinical evidence of acute pancreatitis (increased serum pancreatic enzymes associated with vomiting, abdominal distention, and intolerance when eating)., Results: Ten of 47 HIV patients had increased serum total amylase values; however fewer patients had increased specific pancreatic enzymes: 6 of 47 for pancreatic amylase (range, 1.8- to 19.8-fold normal limit) and 7 of 47 for lipase (range, 1.4- to 4-fold normal limit). Values were normal in all controls. Two HIV patients with increased total amylase had clinically evident parotid inflammation. None of the patients with increased serum pancreatic amylase and/or lipase had clinical symptoms of acute pancreatitis. Regression analysis showed no correlation between increased serum pancreatic enzyme levels and disease progression (CDC class), immunologic status (CD4 count), nutritional status, drug administration, or opportunistic infections., Conclusions: Fifteen per cent of HIV-infected children had biochemical evidence of pancreatic involvement; however, this condition was unrelated to clinical signs of pancreatitis. Neither drug administration nor opportunistic infections seem to determine the increased serum pancreatic enzyme levels.

Previous evidence suggested a role of enterotoxin in the pathophysiology of cryptosporidiosis. If so, antisecretory drugs should be effective in reducing diarrhea. We evaluated the in vivo and in vitro efficacy of octreotide, which possesses antisecretory effects, for cryptosporidial diarrhea. Two children with severe cryptosporidial diarrhea were treated with octreotide. The volume modifications and chemical composition of stools were determined. Fecal supernatant was added to Caco-2 cell monolayers mounted in Ussing chambers with or without serosal octreotide and electrical parameters were monitored. Octreotide was effective in reducing the stool volume and fecal Na+ concentration. Fecal supernatant induced an enterotoxin-like increase in transepithelial potential difference. Octreotide induced a dose-dependent decrease in basal potential difference, consistent with an absorptive effect. In cells pretreated with octreotide, fecal supernatant induced an increase in the potential difference, whose magnitude and duration were significantly reduced compared to untreated cells. These results provide in vivo and in vitro evidence for the secretory nature of cryptosporidial diarrhea and for the efficacy of octreotide through a direct interaction with the enterocyte.

Background: Oral administration of live Lactobacillus casei strain GG is associated with the reduction of duration of diarrhea in children admitted to the hospital because of diarrhea. The purposes of this work were to investigate the clinical efficacy of oral administration of Lactobacillus in children with mild diarrhea who were observed as outpatients, and to see whether Lactobacillus GG can reduce the duration of rotavirus excretion., Methods: Duration of diarrhea was recorded in 100 children seen by family pediatricians and randomly assigned to receive oral rehydration or oral rehydration followed by the administration of lyophilized Lactobacillus casei, strain GG. Rotavirus was looked for in the stools of all children and in those in whom results were positive, stools were examined again 6 days after the onset of diarrhea., Results: In 61 children results were positive for rotavirus and in 39 results were negative. Duration of diarrhea was reduced from 6 to 3 days in children receiving Lactobacillus GG, with a similar pattern in rotavirus-positive and -negative children. Six days after the onset of diarrhea, stools in only 4 out of 31 children that received Lactobacillus GG were positive for rotavirus compared with positive findings in 25 out of 30 control subjects., Conclusions: Oral administration of Lactobacillus GG is effective in rotavirus-positive and rotavirus-negative ambulatory children with diarrhea. Furthermore, it reduces the duration of rotavirus excretion.

Background: Enteric cryptosporidiosis is a frequent problem in adults with human immunodeficiency virus (HIV) infection, but little is known of its features in children. The aim of this study was to investigate the incidence and the clinical features of cryptosporidiosis in HIV-infected children., Methods: Thirty-five children with symptomatic HIV infection were screened every 2 months, and in case of diarrhea, for the presence of Cryptosporidium. Intestinal function tests were performed, and the fecal osmotic gap was measured in children with cryptosporidiosis., Results: Seventy episodes of diarrhea occurred in 16 children in a median period of 17 months. Cryptosporidium was detected in five cases, all with full-blown acquired immunodeficiency syndrome. Cryptosporidiosis was significantly more protracted than any other form of diarrhea and was associated with dehydration and severe weight loss. Intestinal function was not modified during cryptosporidiosis. Osmotic gap values were consistent with secretory rather than osmotic diarrhea. In four cases, recovery was observed without specific treatment., Conclusions: Enteric cryptosporidiosis is a severe problem in advanced stages of HIV infection. It does not induce intestinal malabsorption. It induces diarrhea of secretory type. Recovery may be observed independently of therapy.

We describe a human immunodeficiency virus-negative infant with chronic intractable diarrhea due to Cryptosporidium parvum; he had a history of significant weight loss since the second week of life. A preliminary study of his immune function was negative for primary immunodeficiency. To further study his immune function, proliferation of peripheral blood mononuclear cells (PBMCs) was elicited by crude antigenic extract from C. parvum oocysts (CCE). Supernatants of CCE-stimulated PBMCs contained interleukin 10 but not interferon gamma (IFN-gamma), while PBMCs from a control (a 2-year-old immunocompetent infant who had recovered from cryptosporidiosis) showed a strong response to IFN-gamma when stimulated with CCE. These results stress the role of IFN-gamma in recovery from cryptosporidiosis.

Severe and protracted diarrhea (SPD) is the most severe form of diarrhea in infancy and has also been defined as intractable diarrhea. Its etiology is poorly defined. We have retrospectively evaluated the etiology, the outcome, and the risk factors of 38 children, admitted with protracted diarrhea and need for total parenteral nutrition (TPN) from 1977 to 1993. Children with anatomic abnormalities and/or primary immunodeficiency were excluded. There was an inverse relationship between the number of patients and the age of diarrheal onset (mean age, 2.9 +/- 3.5 months). Etiology of SPD was an enteric infection in 18 cases (eight Salmonella, three Staphylococcus, five rotavirus, one adenovirus, one Cryptosporidium), multiple alimentary intolerance (eight cases), familial microvillous atrophy (two), autoimmune enteropathy (two), celiac disease, lymphangectasia, eosinophilic enteropathy, intestinal pseudoobstruction, and intestinal neurodysplasia (1 case each). Etiology was not detected in three cases. Overall, 12 children died, five are presently being treated, and 21 had full remission. Comparative evaluation of risk factors between children with SPD and a control population of children with diarrhea but without the need for TPN showed that low birth weight, no breast feeding, history of fatal diarrhea in a relative, and early onset of diarrhea had a significantly higher incidence in the former. Social background was similar in the two populations. We conclude that a specific etiology can be identified in the majority of cases of SPD. The etiologic spectrum of SPD is broad, but an enteric infection is the most common cause of SPD. The severity of this condition is related, at least in part, to established risk factors.