Resting energy expenditure in children newly diagnosed with stage IV neuroblastoma

Children with stage IV neuroblastoma (NBIV) are often malnourished at time of diagnosis, observed as high as 50%. The emphasis of this study was to determine whether an increased resting energy expenditure (REE) is a causative factor. Our hypothesis was that children diagnosed with NBIV have an increased REE, which normalizes with cancer treatment. Changes in nutritional status from time of diagnosis in response to nutritional support were examined. REE and nutritional evaluation were obtained three times: at diagnosis before starting treatment, where tumor burden is expected to be highest; after two courses of chemotherapy, where some response to treatment is expected; and after surgical excision of the primary tumor, where there was presumably minimal residual disease. Ten subjects completed the study. Results showed that REE was not increased, and there was no significant difference between phases (p = 0.29). Fifty percent of our subjects were malnourished at diagnosis. Because REE is not increased in NBIV, it is concluded that malnutrition seen in NBIV is not due to increased energy needs, but is likely due to decreased intake because of the intra-abdominal mass and malignant malaise.     

Cardiac hamartomas in Bourneville's tuberous sclerosis. Perinatal echographic diagnosis and spontaneous evolution]

Cardiac hamartomas are frequently the earliest revelation of Bourneville's tuberous sclerosis. They sometimes allow to consider the diagnosis during the antenatal period, and to plan therefore genetic and CNS investigations. After the neonatal period, the evolution of hamartomas is frequently favourable, characterised with at least partial involution. OBSERVATION: Antenatal equivocal cardiac echographic images did not allow the diagnosis in a fetus whose father had Bourneville's disease. Other antenatal investigations (genetics, central nervous system MRI) were not helpful. The diagnosis was carried out at birth as cardiac ultrasound reliably showed two cardiac hamartomas. CONCLUSION: Even when suspected, the antenatal diagnosis of Bourneville's disease is difficult. The presence of cardiac hamartomas at birth is a reliable mean to make the diagnosis.     

Celiac disease: clinical characteristics and methods used in the diagnosis of patients registered at the Brazilian Celiac Association

OBJECTIVE: To evaluate the clinical characteristics and methods used in the diagnosis of patients registered at the Brazilian Celiac Association (BCA). METHODS: A questionnaire about clinical characteristics and diagnostic methods in celiac disease was mailed to 584 members of the BCA. RESULTS: We received 292 responses for 584 questionnaires mailed (49.5%). The clinical characteristics of celiac disease in the sample we analyzed showed that the most frequent type was the classical mode (88.9%), while the atypical mode was present in only 11.1% of patients at the time of diagnosis. Increased incidence of both late diagnosed classical mode (44.5% to 64.2%; P=.004) and atypical mode (5.2% to 16.8%; P=.005) has been observed in the last 5 years. Duration of symptoms before diagnosis was greater than 1 year in 75% patients with atypical manifestation. Intestinal biopsy was not performed in 19% of the cases at the time of diagnosis. It was observed that in the last 5 years intestinal biopsy was not performed for a larger number of patients (24.4%) than in the previous period (only 11.1%) (P=.007). CONCLUSIONS: Classical mode is still the most frequent clinical manifestation of celiac disease. The late diagnosed classical mode is predominant, but our findings show an increase in the proportion of the atypical mode. Although characterization of subtotal or total villous atrophy of the intestinal mucosa is of paramount importance to the diagnosis of celiac disease, 19% of the patients diagnosed for celiac disease did not undergo intestinal biopsy at the time of diagnosis, most notably in the last 5 years.     

Gastrointestinal bleeding in a 15 month old male. A presentation of Munchausen's syndrome by proxy

Munchausen's syndrome by Proxy is a well-described entity that may not always be immediately considered in a complicated case. We describe this syndrome being portrayed through the guise of gastrointestinal bleeding in a 15 month old male and discuss not only the difficulty involved in solidifying this diagnosis but also the consequences that may occur should this diagnosis not be entertained. Failure to diagnose Munchausen's syndrome by proxy often results from failure to consider the diagnosis. These cases frequently have specific characteristics that allow seasoned clinicians to suspect the diagnosis. Once the diagnosis is considered, it is crucial to take steps to protect not only the index patient but also siblings who not infrequently are also recipients of this life threatening form of child abuse.     

Aseptic femur head osteonecrosis during treatment of acute lymphoblastic leukemia in the child]

Avascular femoral head necrosis (AFN) is an uncommon complication of acute lymphoblastic leukemia (ALL) occurring in association with serious functional late effects. One of the many risk factors is high-dose corticosteroid therapy. CASE REPORT: Three children belonging to a series of 266 patients developed AFN. The diagnosis was not made immediately when X-rays were normal. In spite of the fact that treatment was begun as soon as possible, the three children had a difference in the length of their legs, with reduction of their walking perimeter and, in one case, an arthroplasty was necessary. CONCLUSION: If some patients treated for ALL limp or suffer when walking or when practising sports, the diagnosis of AFN is to be evoked. The diagnosis is not only based on simple X-rays but also on magnetic resonance imaging, which is more sensitive and reveals lesions earlier. The treatment consists of immobilization of the hip, whether or not associated with surgical procedures.     

The evolution of diagnostic trends in congenital heart disease: A population-based study

OBJECTIVE: To analyse historical trends in diagnosis of congenital heart disease (CHD) in all diagnosed cardiac malformations born between 1945 and 1994 in a population-based study, the first of its type. METHODOLOGY: Retrospective analysis of age and mode of diagnosis was carried out in 953 patients with CHD, in the setting of a regional hospital providing diagnostic and follow up services for all of Malta. Main outcome measures were age at diagnosis, cumulative percentage diagnosis by age and mode of diagnosis. RESULTS: A significant negative correlation of age at diagnosis with time was found for both lesions not requiring intervention, and requiring intervention (P < 0.0001). Cumulative percentage diagnosis by age increased progressively with time. Echocardiography increased the birth prevalence of definitively diagnosed defects, particularly of lesions not requiring intervention. The annual number of cardiac catheters for these conditions has decreased with an increased number and proportion of interventional catheters. The current catheterization rate for CHD is 6.1/100 000 population. CONCLUSION: Echocardiography has led to an increase in the diagnosis in the birth prevalence of CHD, and provided early diagnosis, supplanting cardiac catheterization as a primary diagnostic tool.     

Difficulties in the diagnosis of Kawasaki disease

This study aims to highlight the difficulties faced in the clinical diagnosis of Kawasaki Disease (KD) presenting beyond the first week. This is a retrospective study of 25 cases of which only 36% met the criteria for classical and 8% was incomplete KD. Majority (56%) did not meet the criteria for classical KD; at the same time they were not incomplete / atypical cases. Difficulties arise in diagnosis of the cases presenting in the second week, as by that time many of the classical findings disappear or probably have not been present at all. In this scenario high index of suspicion for KD in a child presenting with fever, looking not that sick (Non toxic look) with bulbar conjunctivitis and oral mucositis helped us to reach the diagnosis. We incidentally observed Hyperemia of the Upper Eyelids in 32% of our cases, which might assist in the diagnosis.     

Griscelli syndrome: description of a case with Rab27A mutation

A 7-month-old Turkish boy presented with partial albinism and typical clinical features of an accelerated phase, suggesting the diagnosis of Griscelli syndrome. The diagnosis was confirmed by light microscopic evaluation of hair and a peripheral blood smear. Genetic analysis identified a mutation in the Rab27A gene. He was initiated immunosuppressive treatment but accelerated phase could not be ameliorated. He unfortunately died from multiorgan failure. The finding of partial albinism in children should alert clinicians to consider Griscelli syndrome since simple methods can corfirm the diagnosis and early diagnosis is life-saving.     

Absences as differential diagnosis in children with attention-deficit disorder

OBJECTIVES: Absences are regarded as one of the most important differential diagnosis of attention and resulting school-problems. Attention deficit-symptoms might develop through absences, even though there is no diagnosis of attention-deficit/ hyperactivity disorder or attention-deficit disorder (ADHD or ADD). Routine EEG-wavings are made, in order to exclude epilepsy as a reason for attention-deficits. METHODS: In this paper the EEGs of 8 132 male and female children and adolescents from two hospitals for child and adolescent psychiatry were analyzed retrospectively. The aim of the study was to assess how many patients with absences do occur and whether they do present a specific psychopathology. RESULTS: In summary for the first time diagnosed absences occurred in 0.44 % (N = 12) of the patients in the first centre and in none of the patients in the second centre. The average age was 9.5 years. 50 % of the patients were diagnosed with ADHD. A specific psychopathology of the patients was not found. CONCLUSIONS: There is a minimal occurrence of absences in child and adolescent patients. Therefore it is not a main differential diagnosis, that has to be considered in children with attention-deficit problems. Due to the late age at the time of diagnosis and the possible good treatability with antiepileptics, it is nevertheless important to regard absences as a rare differential diagnosis.     

Delay in diagnosis of Williams syndrome

Williams syndrome (WS) is a well-known genetic disorder with a variable phenotype. In many cases, physical manifestations are subtle and may not be apparent at an early age, making diagnosis difficult in infants and young children who lack classic manifestations such as supravalvular aortic stenosis and hypercalcemia. Clinical suspicion is essential because the diagnostic genetic finding is not detectable on routine chromosomal analysis. Furthermore, early diagnosis allows for earlier detection and treatment of developmental, behavioral, and medical problems. In an effort to understand how and why individuals with WS are diagnosed, we conducted a survey-based study of parents of WS children. Packets containing a cover letter, consent form, parental survey and preaddressed stamped envelope were distributed to parents of children with WS. The survey included questions concerning initial diagnosis, WS findings present, medical specialists involved, and tests performed. Forty-six completed surveys were returned for analysis. The mean age at diagnosis was 3.66 years (SD 4.13). The mean age at which there were initial concerns was 0.98 year (SD 1.24) resulting in a mean delay in diagnosis of 2.77 years (SD 4.10). In addition, the involvement of a geneticists correlated with earlier diagnosis (2.26 years vs. 5.09 years without geneticist involvement, p = 0.03) and fewer tests ordered (5.2 vs. 8.2 in the nongeneticist group, p = 0.0006). We observed a significant delay in the diagnosis of WS. Of note, the involvement of a geneticist was associated with earlier diagnosis and reduced number of tests.     

云南苯丙氨酸羟化酶基因内(TCTA)n多态性及其在苯丙酮尿症诊断中的应用

目的应用苯丙氨酸羟化酶（ＰＡＨ）基因内（ＴＣＴＡ）ｎ多态性连锁分析进行经典型苯丙酮尿症（ＰＫＵ）的基因诊断和产前诊断。方法应用聚合酶链反应扩增片段长度多态性（ＰＣＲＡｍｐＦＬＰ）方法,分析云南省１３个家系苯丙氨酸羟化酶（ＰＡＨ）基因内（ＴＣＴＡ）ｎ多态性。结果在１３个家系中检测到２２４～２５２ｂｐ的８种等位片段,其ＰＩＣ为０．６９８,杂合频率是５１％。可诊断率为１００％和５０％的家系各６个,１个家系因双亲带型为纯合型而未能诊断,可诊断率为６９％。完成１例产前基因诊断和２例回顾性的基因诊断。结论（ＴＣＴＡ）ｎ的ＰＣＲＡｍｐＦＬＰ分析可作为经典型ＰＫＵ基因诊断和产前诊断的一种简便有效的方法。     

Prenatal diagnosis of autosomal recessive polycystic kidney disease]

OBJECTIVE: Prenatal ultrasonographic detection of autosomal recessive polycystic kidney disease (ARPKD) is of poor reliability, especially in early pregnancy. Molecular genetics allows earlier diagnosis, from 11 weeks of gestation; however, since only indirect diagnosis is possible--the ARPKD gene being localized on chromosome 6 but not identified--the feasibility of molecular diagnosis requires several conditions: definitive diagnosis in the index case, availability of index case and parents' DNA, genetic informativity of the family at the ARPKD locus. Results and limits of this method are analyzed, using a series of 56 requests for prenatal diagnosis. RESULTS: In eight of the 56 families ARPKD was excluded on the basis of histological (seven cases) and/or genetic (two cases) criteria. Molecular study was impossible in three families due to the lack of index case's DNA, and two other families were non-informative. Among the 43 families in which prenatal diagnosis was feasible, analysis of the haplotype of 35 fetuses issued from 29 families showed that 11 fetuses with the same haplotypes as that of the index case were affected, while 24 were not. No false positive or false negative result was reported. CONCLUSIONS: Early and reliable prenatal diagnosis of recessive polycystic kidney disease is possible in nearly 80% of affected families.     

Microvillous inclusion disease diagnosed by gastric biopsy

Protracted diarrhea in neonates is uncommon and usually requires an intestinal biopsy for etiological diagnosis. Gastric biopsy has not been used in the routine diagnosis of this condition. We report the first documented patient with microvillous inclusion disease from India, where the diagnosis was established by a gastric biopsy.     

Second trimester antenatal diagnosis in rare coagulation factor deficiencies

Prenatal diagnosis is sought after for those genetic disorders, whose management is not satisfactory either because of the outcome or owing to extreme cost involved in the management of the patients affected by a specific disorder. Severe hemophilia and homozygous thalassemia are the 2 disorders for which there is an increasing demand for prenatal diagnosis in India. Rare severe deficiencies of coagulation factor X (FX) and factor VII (FVII) may present with severe bleeding manifestations. Because of their rarity the laboratory offering prenatal diagnosis for severe hemophilia and thalassemia may not be in a position to provide genetic diagnosis in the fetus. In this communication, we describe 2 families, 1 with an index patient of severe FVII deficiency and the other with severe FX deficiency where successful prenatal diagnosis was given after cordocentesis between 17 and 19 weeks using a battery of coagulation factor assays. Follow-up studies were performed 3 to 4 months after delivery and the diagnoses were reconfirmed on these babies by a repeat factor assay for FX and FVII deficiency, respectively.     

An algorithmic approach to diagnosis of hypoglycemia

An algorithm has been devised to facilitate the diagnostic approach to the causes of hypoglycemia. This systematic approach enables the physician to reach the final diagnosis in a logical way without subjecting the child to unnecessary and possibly hazardous investigations. The algorithm is based on the following measurements as required by each patient: concentrations of blood glucose, lactate, ketone bodies, and glucose-regulating hormones. These measurements are performed with the patient in the fasting state and after loading tests (glycerol and galactose) as needed. If indicated, an enzymatic test is performed to establish the final diagnosis. Eighteen children aged 1 month to 7 years who had persistent or recurrent hypoglycemia have been examined according to this algorithm. The correct diagnosis was arrived at in 17 patients. The diagnosis was not reached in one neonate who had glucose-6-phosphatase deficiency and initially did not have lactic acidosis; once lactic acidosis developed, his illness fitted perfectly into the algorithm.     

Diagnostic delay in neurofibromatosis type 1

Since 1985 a multidisciplinary team in the Sophia Children's University Hospital in Rotterdam provides diagnostic follow up and genetic counselling services for neurofibromatosis type 1 (NF1) patients and their families. Parents of 68 affected children as well as 24 affected parents were interviewed. Of the affected children, 50% and 33% of the affected adults were treated for symptoms related to NF1 before a specific diagnosis was made. Although the disease is fully penetrant by the age of 5 years, 35% of the affected children had not been diagnosed by this age. Parents stated a preference for early diagnosis of NF1. Diagnosis of NF1 did not seem to be a reason to refrain from having children. The general attitude towards prenatal diagnosis was positive; however few parents would actually terminate an affected pregnancy. Conclusion Overall delay in diagnosis of NF1 is significant. Knowledge of symptoms should make an early diagnosis possible with beneficial effects for the patient and family members. Received: 25 July 1996 / Accepted: 21 October 1996     

Abdominal tuberculosis in children: an Indian experience

The hospital records of 125 children, aged 14 years or less treated for abdominal tuberculosis (TB) at Jawahar Lal Nehru Medical College and Hospital, Ajmer, India between January 1987 and December 1996, were studied to analyse the various patterns of abdominal TB in children and to evaluate the role of various investigations in researching a diagnosis. Abdominal pain was the presenting symptom in 100 (80 per cent) patients. Detectable ascites was present in 55 (44 per cent) and visible peristalsis in 45 (36 per cent) cases. Laboratory investigations and radiographs were not conclusive in the majority of the patients. In 45 (36 per cent) patients in whom no tissue diagnosis was available, the diagnosis was based on a dramatic clinical response to anti-tuberculous chemotherapy. Fifty (40 per cent) patients were treated conservatively with anti-tuberculous drugs alone; the remaining patients underwent laparotomy for diagnosis and relief of bowel obstruction. There were no post-operative deaths and on follow-up, good recovery was observed in these patients. Abdominal TB in children is of a non-specific nature and defies diagnosis with non-invasive investigations; laparotomy is required for a definitive diagnosis in the majority of the patients. However, if a high index of suspicion is maintained in endemic areas, a therapeutic trial of anti-tuberculous chemotherapy is justified.     

Ultrasonographic evaluation of abdominal masses in children

Ultrasonography is a recently acquired diagnostic modality in our sub-continent. The initial experiences with this technique in 55 children with abdominal masses are presented. In 15 children ultrasonography merely confirmed the diagnosis which was arrived at by other means; a positive contribution towards the final diagnosis was made in 33 children, while in 7, ultrasonography did not contribute towards the diagnosis. The scope, advantages and pitfalls of ultrasonography are briefly discussed.     

Ultrasonographic evaluation of abdominal masses in children

Ultrasonography is a recently acquired diagnostic modality in our sub-continent. The initial experiences with this technique in 55 children with abdominal masses are presented. In 15 children ultrasonography merely confirmed the diagnosis which was arrived at by other means; a positive contribution towards the final diagnosis was made in 33 children, while in 7, ultrasonography did not contribute towards the diagnosis. The scope, advantages and pitfalls of ultrasonography are briefly discussed.     

Rapid diagnosis of malignancy using flow cytometry

The rapid and accurate diagnosis of childhood malignancy is important both in the planning of appropriate treatment and in relieving the inevitable family anxiety. The use of flow cytometry to analyse monoclonal antibody coated single cell suspensions is widely accepted as having increased the speed and accuracy of diagnosis in leukaemias, though its use in solid tumour diagnosis is not widely reported. Ten cases of childhood malignancy in whom the diagnosis was initially made by flow cytometry and subsequently confirmed histologically are described. The technique has a number of advantages. Only a small sample is required as the analysis is carried out on a single cell suspension, the method is rapid, a diagnosis being reached within three hours of receipt of the sample, and information is obtained on cell lineage and stage of differentiation. Diagnostic accuracy is good when compared with histological results.