Eva Gross-Kieselstein

Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A, not MYO5A

Griscelli syndrome (GS), a rare autosomal recessive disorder, is characterized by partial albinism, along with immunologic abnormalities or severe neurological impairment or both. Mutations in one of two different genes on chromosome 15q can cause the different subtypes of GS. Most patients with GS display the hemophagocytic syndrome and have mutations in RAB27A, which codes for a small GTPase. Two patients with neurological involvement have mutations in MYO5A, which codes for an actin-based molecular motor. The RAB27A and MYO5A gene products interact with each other and function in vesicle trafficking. We report the molecular basis of GS in a Muslim Arab kindred whose members have extremely variable neurological involvement, along with the hemophagocytic syndrome and immunologic abnormalities. The patients have normal MYO5A genes but exhibit a homozygous 67.5-kb deletion that eliminates RAB27A mRNA and immunocytofluorescence-detectable protein. We also describe the molecular organization of RAB27A and a multiplex polymerase chain reaction assay for the founder deletion in this kindred. Finally, we propose that all patients with GS have RAB27A mutations and immunologic abnormalities that sometimes result in secondary neurological involvement. The two patients described elsewhere who have MYO5A mutations and neurological complications but no immunologic defects may not have GS but instead may have Elejalde syndrome, a condition characterized by mild hypopigmentation and severe, primary neurological abnormalities.

Bloody diarrhea--a possible complication of sulfasalazine transferred through human breast milk.

Sulfasalazine very rarely causes bloody diarrhea. A 3-month-old infant had bloody diarrhea that could be related to sulfasalazine that had been taken by his mother and was transferred through his mothers breast milk. The patient was exclusively breast fed, and no other known etiological factors could be detected for the infants bloody diarrhea.

Pancreatitis as a complication of Henoch--Schonlein purpura.

A 5-year-old girl suffering from Henoch--Schonlein purpura developed severe abdominal pain accompanied by vomiting and fever. Concomitantly, the serum amylase level became elevated and leukocytosis developed, with a shift to the left. A diagnosis of pancreatitis complicating Henoch--Schonlein purpura was made. This rare complication is presented, along with a review of the literature.

Two novel mutations identified in familial cases with Donohue syndrome

Donohue syndrome (DS) is a rare and lethal autosomal recessive disease caused by mutations in the insulin receptor (INSR) gene, manifesting marked insulin resistance, severe growth retardation, hypertrichosis, and characteristic dysmorphic features. We report the clinical, molecular, and biochemical characterization of three new patients with DS, and address genotype–phenotype issues playing a role in the pathophysiology of DS. A female infant born to first‐degree cousins Muslim Arab parents and two brothers born to first‐degree cousins Druze parents presented classical features of DS with hypertrophic cardiomyopathy and died in infancy. Each patient was found homozygous for one missense mutation within the extracellular domain of the INSR gene. Western blot analysis identified the proreceptor of INSR, but not its mature subunits alpha and beta. Of 95 healthy Muslims, no heterozygous was found and of 52 healthy Druze from the same village, one was heterozygous. This study presents two novel familial mutations in the alpha subunit of the INSR which appear to impair post‐translational processing of the INSR, resulting loss of its function. Both mutations cause DS with hypertrophic cardiomyopathy and early death. Identification of the causative mutation enables prevention of this devastating disease.

Prostaglandins in small intestinal mucosa of children with celiac disease.

Diarrhea is one of the important clinical symptoms in patients suffering from celiac disease and is attributed mainly to malabsorption. We determined prostanoid content in small intestinal mucosa of five patients with active celiac disease and in a control group consisting of six patients. Prostaglandin E2 and thromboxane B2 content in duodenal mucosa of patients with active celiac disease was 1,581 +/- 161 and 118 +/- 40 pg/mg wet wt, respectively, significantly higher than their content in duodenal mucosa of the control group, 378 +/- 86 and 8 +/- 8, p less than 0.001 and p less than 0.02, respectively. 6-Ketoprostaglandin F1 alpha content in celiac patients was not significantly different from its content in the control group: 908 +/- 437 and 124 +/- 53 pg/mg wet wt, respectively. It is possible that, in celiac disease, increased mucosal prostanoid content may contribute, at least in part, to intestinal electrolyte and fluid secretion and consequent diarrhea.

Intestinal protein loss and hypoalbuminemia in children with pneumonia.

Background Intestinal protein loss has been reported mainly in diseases affecting the gastrointestinal tract. Intestinal protein loss during pneumonia with effusion has not been reported to date. The authors attempted to assess the associations between pneumonia with effusion and intestinal protein loss and hypoalbuminemia in children. Methods This was a prospective consecutive case series study of in children hospitalized with pneumonia and effusion during a period of 4½ years. Serum albumin, C-reactive protein (CRP), and fecal &agr;-1 antitrypsin (&agr;-1-AT) were measured in the first 72 hours of hospitalization. Two control groups were studied: one consisted of 50 febrile children hospitalized because of viral or mild bacterial infections, and the other consisted of 20 afebrile children hospitalized because of convulsive disorders. Results Sixty-seven children ages 4 months to 14 years hospitalized with pneumonia and effusion were enrolled in the study. Fifty-nine percent (40 children) were found to have elevated fecal &agr;-1-AT excretion (range, 2–10 mg/g) compared with none in the two control groups (P < 0.000). Fifty-two percent (35 children) of the children with pneumonia and effusion had mild to moderate hypoalbuminemia (range, 22–34 g/L). Only one child (2%) in the febrile control group had a low albumin of 34 g/L; none were found in the afebrile control group. The level of fecal &agr;-1-AT was inversely correlated with serum albumin level. Conclusions Pneumonia with effusion in children is often associated with an intestinal protein loss that can be monitored by measuring gastrointestinal loss of protein, namely fecal &agr;-1-AT. In most cases the development of hypoalbuminemia correlates with the development of intestinal protein loss.

Chronic Pigmented Purpura: A Case Report of Schamberg's Disease

The syndrome of chronic pigmented purpura (CPP) consists of pigmented macular lesions, predominantly involving the lower extremities. An 11-year-old girl was diagnosed initially as suffering from vasculitic purpura, but the clinical course and the skin histology proved to be consistent with CPP. This syndrome should be included in the differential diagnosis of childhood purpura.

Usefulness of echocardiography and radionuclide ventriculography for diagnosing buckling of the innominate artery in children

Abstract Buckling of the brachiocephalic arteries is a relatively common anomaly. 1–4 Until now, this anomaly has been diagnosed during life only by angiography or as a postmortem finding. 1–4 To the best of our knowledge, involvement of the innominate artery in pediatric patients has not yet been reported. We present 14 patients with buckling of the innominate artery who were diagnosed by 2-dimensional (2-D) echocardiography and nuclear angiography. In 4 patients angiography was also performed and the diagnosis was confirmed in all.