[An infant with a swelling of the cheek]. / Een pasgeborene met een gezwollen wang.

A 2-weeks-old girl was presented with a swelling of the right parotid gland, due to acute suppurative parotitis caused by Staphylococcus aureus.

Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.

Congenital disorders of glycosylation (CDG) represent a group of inherited multiorgan diseases caused by defects in the biosynthesis of glycoproteins. We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks. Increased activities of lysosomal enzymes in plasma were found, though total sialic acid in plasma was strongly decreased. Isoelectric focusing of serum sialotransferrins showed a type 2-like CDG pattern. Some of the known CDG subtypes were excluded. O-Glycosylation was investigated by isoelectric focusing of apolipoprotein C-III, which showed increased fractions of hyposialylated isoforms. In a consecutive study a defect in the conserved oligomeric Golgi complex was established at the level of subunit COG-7, leading to disruption of multiple glycosylation functions of the Golgi. This report on patients with a new variant of CDG, due to a multiple Golgi defect, emphasizes in addition to sialotransferrins the importance of analysis of a serum O-linked glycoprotein, e.g. apolipoprotein C-III, in unclassified CDG-X cases.

Carnitine-acylcarnitine translocase deficiency: case report and review of the literature.

AIM: Carnitine-acylcarnitine translocase (CACT) deficiency is an inborn error of metabolism involving the mitochondrial beta-oxidation of long-chain fatty acids. The aim of this study was to report on a new case (neonatal phenotype) and review the literature data on 24 previously reported cases. METHODS: Clinical data of the new case are described and compared with the previous reports. RESULTS: The patient with a novel mutation had clinical features and biochemical findings similar to those of the other reported patients. CONCLUSION: CACT is an entity in which clinical encephalopathy, hepatomegaly and arrythmias are common. Hyperammonaemia and elevation of creatine kinase seem to be constant findings as in other disorders of mitochondrial beta-oxidation of long-chain fatty acids. The mortality rate is very high.

[Behçet's disease in a Dutch boy with painful skin lesions]. / De ziekte van Behçet bij een Nederlandse jongen met pijnlijke huidafwijkingen.

A 14-years-old Dutch boy had pain in both calves, recurrent oral ulcers, fever, hoarseness and erythema nodosum-like skin lesions. Laryngoscopic examination revealed a vocal cord ulcer and leukocytoclastic vasculitis was visible in a skin biopsy. Based on the clinical picture, the diagnosis of 'incomplete juvenile Behçet's disease' was established. During treatment with colchicine, genital ulcers developed. These disappeared after local treatment with corticosteroids. Juvenile Behçet's disease is rare in Western Europe and the diagnosis is often difficult. Diagnostic criteria have been formulated, but in most cases there is a delay before these criteria are fulfilled due to the slow clinical course of the disease. All organ systems may be affected; mucocutaneous and skin lesions are the most frequent manifestations. Therapy depends on the severity and the symptoms of the disease.

[Diagnostic image (128). A boy who refused to walk. Spondylodiscitis LIV-LV]. / Diagnose in beeld (128). Een jongetje dat niet meer lopen wil. Spondylodiscitis LIV-LV.

One week after a fall from his buggy, a 2-year-old boy was seen at the first-aid department because he refused to walk. A bone scan and MRI revealed spondylodiscitis at the left side of the discus Liv-Lv and a psoas abscess.

Phenotypic variability of the cat eye syndrome. Case report and review of the literature.

We present a male infant with preauricular skin tags and pits, downslanting palpebral fissures, hypertelorism, ectopic anus, hypospadias, and hypoplastic left heart syndrome. The clinical features in our patient show phenotypic overlap with the cat eye syndrome, as illustrated by the review of 105 reported cases. Cytogenetic analysis revealed a supernumerary marker chromosome, which was identified by microdissection and fluorescence in situ hybridization as an isodicentric chromosome 22(pter --> q11.2::q11.2 --> pter). It was proved with probes specific for the cat eye syndrome critical region that this region was present in quadruplicate in the propositus. We conclude that CES is characterized by large phenotypic variability, ranging from near normal to severe malformations, as reflected in the neurodevelopmental outcome. Preauricular skin tags and/or pits are the most consistent features, and suggest the presence of a supernumerary bisatellited marker chromosome 22 derived from duplication of the CES critical region.

Characterization of a de novo unbalanced translocation t(14q18q) using microdissection and fluorescence in situ hybridization.

We report on a patient with a de novo translocation between the long arms of chromosomes 14 and 18. The translocation was studied using microdissection in combination with fluorescence in situ hybridization (micro-FISH). Five copies of the chromosomes involved in the translocation were isolated by microdissection and amplified by means of degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR). Reverse chromosome painting with the biotin-labeled PCR product showed that part of the q-arm of chromosome 18 had no signal. The deletion was characterized further by FISH with band-specific probes and it was concluded that the rearrangement was unbalanced: 46,XY,t(14;18)(14pter-->14q22::18q21.1-->18qter) (18pter-->18q12.2::14q22-->14qter). The patient, who presented with psychomotor retardation, mild obesity, pes equinovarus, strabismus, and facial anomalies, is compared with previously reported patients with an interstitial deletion of band 18q12.

Does impaired growth of PKU patients correlate with the strictness of dietary treatment? National Dutch PKU Steering Committee.

To assess whether growth retardation in patients with phenylketonuria (PKU) is related to the strictness of their dietary treatment, the relationship between Z scores for height up to 3 y of age and different indices of dietary control in 103 early treated Dutch PKU patients was studied. As indices of dietary control, the mean phenylalanine (Phe) concentration, the frequency of plasma Phe concentrations < 200 and < 120 micromol/l, and the standard deviation of the individual plasma Phe concentrations were studied. These measures of the dietary control were divided into quartiles. The mean Z score of the studied patients showed a decrease of 0.18/y (SD 0.36). No statistically significant difference between any of the quartiles of the studied indices with growth retardation was found. None of the used indices of dietary control based on plasma Phe concentrations showed a relationship between different degrees of the strictness of dietary treatment with growth retardation in Dutch PKU patients.

Clinical outcome and long-term management of 17 patients with propionic acidaemia.

UNLABELLED: A retrospective study was performed on the clinical outcome and long-term treatment of 17 patients with propionic acidaemia diagnosed during the last 20 years in our hospital. The study group consisted of 12 patients with early onset type of disease and 5 patients with late onset. Seven (41%) patients died, five with early onset and two with late onset. The deceased early onset patients had a median survival of 0.4 years while the deceased late onset patients died at the age of 2.8 and 4 years respectively. Median age of the living early onset patients was 5.2 (1-9.25) years, the late onset patients were 4, 7 and 23 years old. Patients were all treated with natural protein restriction and in most cases carnitine and metronidazole were added. The early onset patients were almost all treated with daily home tube feeding. The mean natural protein intake of early onset patients (6.3 +/- 1.5 g/day) was significantly lower than the natural protein intake of late onset patients (17.6 +/- 5.3 g/day). Supplemental protein intake was higher in early onset patients. The general neurological outcome of our study group was satisfactory with a better outcome for early onset patients. As to growth, many patients showed a failure to thrive, this was particularly for height. The strong protein restriction during the first years of life probably contributed to this. CONCLUSION: The prognosis for patients with propionic acidaemia appeared to be satisfactory in terms of survival and outcome characteristics such as neurological and mental development. Despite these results the authors feel that the prognosis and quality of life of these patients might be improved with liver transplantation or possibly somatic gene therapy in the future.

Clinical outcome of long-term management of patients with vitamin B12-unresponsive methylmalonic acidemia.

We performed a retrospective study of all patients with methylmalonic acidemia diagnosed during the past 20 years. Only those patients who were nonresponsive to vitamin B12 in vivo and in vitro were included. The final study group consisted of 26 patients, of whom 16 had a neonatal (early) onset; in 10 patients the diagnosis was made after 2 months to 2.2 years (late onset). Of the early-onset patients, 14 (87%) died, with a mean survival time of 1.5 years (range, 10 days to 2.5 years), whereas four of the late-onset patients (40%) died (range, 1.2 to 15 years). At present, eight patients are alive; their mean age is 4.6 years (range, 1 to 10 years). In the early 1970s, treatment was based on the principles of treating patients with phenylketonuria: restricting natural protein intake and supplementing essential amino acids, vitamins, and trace elements. After about 1980, nasogastric tube feeding became a mainstay of the therapy, natural protein restriction became stricter, and the use of essential amino acid mixtures diminished. Carnitine was added to the therapy and, in later years, metronidazole. Since these changes were implemented, the number of episodes of metabolic decompensation and hospitalizations has decreased. Mean survival time of the patients, in particular those with early onset, has only slightly improved, partly because of psychosocial problems in many of these families. Almost all the patients, especially those with early onset, had some degree of neurologic impairment and mental retardation, and many patients were at less than 2 SD for weight or height or both. In contrast, the neurologic and mental status of the late-onset patients was frequently normal, and their weight and height were more often within normal limits. Our results show that the treatment of methylmalonic acidemia still poses considerable problems; despite intense medical efforts and familial stress, the prognosis for the early-onset patients is disappointing. The patients with late-onset disease, however, appear to have a fairly good prognosis with the present therapeutic approach. Liver transplantation or possibly genetic therapy might improve our results in the future.

Recurrent episodes of bizarre behavior in a boy with ornithine transcarbamylase deficiency: diagnostic failure of protein loading and allopurinol challenge tests.

Recurrent episodes of bizarre behavior were the only clinical symptoms that finally led to the diagnosis of ornithine transcarbamylase deficiency in an 8-year-old boy. The suspected diagnosis could not be confirmed with the use of current challenge tests. The response to a high-protein diet for 24 hours appeared to be a helpful diagnostic aid.

[Chronic recurrent abdominal pain in school children]. / Chronisch recidiverende buikpijn bij schoolkinderen.

The diagnostic approach of children with recurrent abdominal pain (RAP) was investigated by means of a standard protocol. The protocol consisted of recently developed laboratory techniques and 'routine' investigations. In addition, all patients were subjected to an extensive psychological investigation. The main results show that in a high percentage (42%) of patients organic abnormalities could be found. Particularly the small bowel seemed to be involved in the pathogenesis of the complaints. Furthermore, gastro-esophageal reflux appeared to be present in as many as 50% of the patients investigated and there might be a relationship with the abdominal pain complaints. Helicobacter pylori did not appear to play an important role in these patients. Comparing the results of the psychologic investigation with a pain-free control group, we did not find clear evidence that psychological factors play a role in the pathogenesis of these patients' complaints. Children with RAP, particularly when complaints exist longer than 6 months, need to be investigated for the presence of organic abnormalities that might provide an explanation for the complaints.

Problem effectiveness in a course using problem-based learning.

BACKGROUND: Problem-based learning (PBL) emphasizes active generation of learning issues by students. Both students and teachers, however, tend to worry that not all important knowledge will be acquired. To explore this question, problem effectiveness (i.e., for each problem, the degree of correspondence between student-generated learning issues and present faculty objectives) was examined in three interdependent studies. METHOD: The three studies used the same participants: about 120 second-year students and 12 faculty tutors in a six-week course on normal pregnancy, delivery, and child development at the medical school of the University of Limburg in The Netherlands, 1990-91. The participants were randomly assigned to 12 tutorial groups that were each given the same 12 problems; the problems were based on 51 faculty objectives; the tutors were asked to record all learning issues generated by their groups. Study 1 addressed this question: To what degree are faculty objectives reflected by student-generated learning issues? Study 2: To what extent do students miss certain objectives, and are these objectives classifiable? Study 3: Do students generate learning issues not expected by the faculty, and are these issues relevant to course content, and finally, why do students generate these issues? To help answer these questions, the studies employed expert raters and a teacher familiar with the course content. RESULTS: Study 1: For the set of 12 problems, the average overlap between learning issues and faculty objectives was 64.2% with the percentages for individual problems ranging from 27.7% to 100%. Study 2: Of the 51 objectives, 30 were not identified by at least one tutorial group; these objectives were grouped into three categories; on average, each group failed to identify 7.4 objectives (15%). Study 3: Of 520 learning issues, 32 (6%) were unexpected; 15 of these were judged to be at least fairly relevant to course content; they were grouped into four categories. CONCLUSIONS: The students' learning activities covered an average of 64% of the intended course content; in addition, the students generated learning issues not expected by the faculty, and half of these issues were judged relevant to the course content. Thus, PBL seems to permit students to adapt learning activities to their own needs and interests.

The prevalence of Helicobacter pylori serum antibodies in children with recurrent abdominal pain.

As part of a large, prospective study we investigated the prevalence Helicobacter pylori serum antibodies in children with recurrent abdominal pain (RAP). All patients suffered from recurrent bouts of abdominal pain for at least 6 months and ranged in age from 6 to 12 years. H. pylori antibodies were detected using an enzyme-linked immunosorbent assay. The prevalence of H. pylori antibodies in the RAP group was compared to that of a control group which consisted predominantly of pre-operative children. None of the control group suffered or had suffered from RAP. Antibodies to H. pylori were found in 7 of 82 (8.5%) RAP patients and in 2 of 39 (5.1%) control children. The latter difference is not significant and suggests that RAP is only rarely caused in children by H. pylori infection.

Gastroesophageal reflux in children with recurrent abdominal pain.

In this study we investigated the presence of gastroesophageal reflux in children with recurrent abdominal pain and its possible relationship to food intolerance-associated duodenal inflammation. Twenty-four-hour intra-esophageal pH monitoring, an endoscopic duodenal biopsy and a small bowel 51Cr-EDTA permeability test were performed in 25 children with recurrent abdominal pain. In 14 cases (56%) the pH monitoring was abnormal, pointing to the presence of pathological gastroesophageal reflux. Treatment of gastroesophageal reflux in the latter patients resulted in resolution or improvement of abdominal pain in 10 cases (71%). Gastroesophageal reflux did not appear to be associated with either intestinal permeability to 51Cr-EDTA or duodenal biopsy findings. We conclude that pathological gastroesophageal reflex is a frequent finding in children with recurrent abdominal pain, that it is unrelated to duodenal inflammation and that there might be a causal relationship between pathological gastroesophageal reflux and recurrent abdominal pain in children.

Gas chromatography method for the separation of amino acids enantiomers in plasma and urine. Application in a case of short bowel syndrome.

Urinary amino acids were isolated from the urine of healthy controls and a patient with a short bowel syndrome. Following derivatization with isopropyl alcohol/HCl and trifluoroacetic anhydride the amino acid enantiomers were separated by gas chromatography on a Chirasil-L-Val column. All subjects excreted D-alanine (10-30% of total Ala). The percentage D-alanine was higher in the patient with the short bowel syndrome. The excretion of D-alanine did not correlate with the D-lactate excretion. An intestinal origin for the D-amino acids is the most probable explanation.

Accumulation of odd-numbered long-chain fatty acids in fetuses and neonates with inherited disorders of propionate metabolism.

Fetuses affected with propionic acidemia incorporate great amounts of odd-numbered long-chain fatty acids (OLCFA) into their body lipids. This is due to abundant supply with precursor amino acids of propionyl-CoA throughout pregnancy. After birth, the lower provision of precursor amino acids during dietary treatment compared with fetal life results in a decline of propionyl-CoA production and therefore OLCFA synthesis. However, the observed decrease of OLCFA may also partly reflect the recovery from acute ketoacidotic episodes that the patients experienced soon after birth as long as they were undiagnosed. In a patient with vitamin B12-responsive methylmalonic aciduria treated prenatally with large doses of vitamin B12 given to the mother, the cord plasma lipids contained normal amounts of OLCFA. This indicates that prenatal therapy led to an increased flux of propionyl-CoA through the defective methylmalonyl-CoA mutase step. Thus, in addition to the quantification of a decline in methylmalonic acid in maternal urine, OLCFA in cord blood lipids might be a further parameter for evaluating prenatal treatment in patients with vitamin B12-responsive methylmalonic aciduria.

Abnormal small bowel permeability and duodenitis in recurrent abdominal pain.

Thirty nine children with recurrent abdominal pain aged between 5.5 and 12 years, underwent endoscopic duodenal biopsy to find out if there were any duodenal inflammatory changes, and if there was a relationship between duodenal inflammation and intestinal permeability to 51Cr-EDTA. Duodenal inflammation was graded by the duodenitis scale of Whitehead et al (grade 0, 1, 2, and 3). In 13 out of 39 patients (33%) definite signs of inflammation were found (grade 2 and 3). Intestinal permeability to 51Cr-EDTA in patients with duodenitis (grade 1, 2, and 3) was significantly higher (4.42 (1.73)%) than in patients with normal (grade 0) duodenal biopsy appearances (3.3 (0.9)%). A significant association was found between duodenal inflammation and abnormal intestinal permeability. Our results give further evidence that there is an intestinal origin of these patients' complaints.