Fatal infectious mononucleosis: A case with a review of the literature

The association of Landry-Guillain-Barre syndrome and other complications with Epstein-Barr virus induced infectious mononucleosis in a 7 yr old girl is being reported from India for the first time.     

Roentgenologic features of the Meckel syndrome

The Meckel syndrome is an autosomal recessive lethal malformation syndrome. The main features are multicystic dysplastic kidneys, microcephaly with occipital encephalocele and polydactyly. This paper describes 6 new cases, with special reference to skeletal findings in postmortem total body radiographys. Microcephaly with an occipital bone defect and encephalocele or hydrocephaly [1/6], short upper extremities, bell-shaped thorax with abdominal distension and postaxial polydactyly in the hands and feet were constant findings in these cases.     

Mitochondrial DNA depletion syndrome causing liver failure

Background

Mitochondrial DNA depletion syndromes are disorders of Mitochondrial DNA maintenance causing varied manifestations, including fulminant liver failure.

Case characteristics

Two infants, presenting with severe fatal hepatopathy.

Observation

Raised serum lactate, positive family history (in first case), and absence of other causes of acute liver failure.

Outcome

Case 1 with homozygous mutation, c.3286C>T (p.Arg1096Cys) in POLG gene and case 2 with compound heterozygous mutations, novel c.408T>G (p.Tyr136X) and previously reported c.293C>T (p.Pro98Leu), in MPV17 gene.

Message

Mitochondrial DNA depletion syndrome is a rare cause of severe acute liver failure in children.     

The widened spectrum of multiple cartilaginous exostosis (MCE)

2 brothers with possible homozygous multiple cartilaginous exostosis (MCE) are reported. The MCE-PD-(Peripheral Dysostosis) syndrome is discussed. A family (father, daughter and son) with Metachondromatosis is presented, and the tendency to spontaneous remission in this condition is emphasized. A “second thought”, when considering the diagnosis of MCE, seems worthwhile.     

The Joubert Syndrome associated with bilateral chorioretinal coloboma

A case of the Joubert Syndrome is reported. This syndrome, of which 11 cases have hitherto been described, is characterized by aplasia of the cerebellar vermis in addition to episodic hyperpnoea, abnormal eye movements, rhythmic protrusion of the tongue, ataxia, and mental retardation. The diagnosis was made by the clinical symptoms, computerized axial tomography of the brain, and lumbar pneumencephalography. Bilateral typical colobomata of retina and choroid were an additional anomaly, described for the first time in association with the Joubert Syndrome. The possible relationship between the ocular and cerebral anomalies is discussed.     

Genetic Analysis in Bartter Syndrome from India

Bartter syndrome is a group of inherited, salt-losing tubulopathies presenting as hypokalemic metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism. Around 150 cases have been reported in literature till now. Mutations leading to salt losing tubulopathies are not routinely tested in Indian population. The authors have done the genetic analysis for the first time in the Bartter syndrome on two cases from India. First case was antenatal Bartter syndrome presenting with massive polyuria and hyperkalemia. Mutational analysis revealed compound heterozygous mutations in KCNJ1(ROMK) gene [p(Leu220Phe), p(Thr191Pro)]. Second case had a phenotypic presentation of classical Bartter syndrome however, genetic analysis revealed only heterozygous novel mutation in SLC12A gene p(Ala232Thr). Bartter syndrome is a clinical diagnosis and genetic analysis is recommended for prognostication and genetic counseling.     

Don’t miss patients with atypical FMR1 mutations: dysmorphism and clinical features in a boy with a partially methylated FMR1 full mutation

Fragile X syndrome characterized by intellectual disability (ID), facial dysmorphism, and postpubertal macroorchidism is the most common monogenic cause of ID. It is typically induced by an expansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene on Xq27 to more than 200 repeats. Only rarely patients have atypical mutations in the FMR1 gene such as point mutations, deletions, or unmethylated/partially methylated full mutations. Most of these patients show a minor phenotype or even appear clinically healthy. Here, we report the dysmorphism and clinical features of a 17-year-old boy with a partially methylated full mutation of approximately 250 repeats. Diagnosis was made subsequently to the evaluation of a FMR1 premutation as the cause for maternal premature ovarian failure. Dysmorphic evaluation revealed no strikingly long face, no prominent forehead/frontal bossing, no prominent mandible, no macroorchidism, and a head circumference in the lower normal range. Acquisition of a driving license for mopeds and unaccompanied rides by public transport in his home province indicate rather mild ID (IQ?=?58). Conclusion: This adolescent demonstrates that apart from only minor ID, patients with a partially methylated FMR1 full mutation present less to absent pathognomonic facial dysmorphism, thus emphasizing the impact of family history for a straightforward clinical diagnosis.     

No relationship between mode of delivery and neonatal mortality and neurodevelopment in very low birth weight infants aged two years

Background

To compare neonatal mortality and neurodevelopmental outcomes at two years of age in very low birth weight infants (≤1500 g) born by cesarean with those by vaginal delivery.

Methods

In this retrospective, case-control study, we evaluated neonatal mortality, medical conditions and neurodevelopmental outcomes at two years of corrected age in 710 very low birth weight (VLBW) infants born between January 2005 and December 2010. Of the 710 infants, 351 were born by the cesarean and 359/710 by vaginal route.

Results

There were no significant differences in neonatal mortality between the cesarean delivery group and vaginal delivery group [56/351 (15.9%) vs. 71/359 (19.8%), P=0.20]. VLBW infants delivered by the cesarean procedure had a higher incidence of respiratory distress syndrome than those born by the vaginal route [221/351 (63.0%) vs. 178/359 (49.6%), P<0.001]. There were no differences in other neonatal morbidities, including intraventricular hemorrhage [126/351 (35.9%) vs. 134/359 (37.3%), P=0.69], bronchopulmonary dysplasia [39/351 (11%) vs. 31/359 (8.6%), P=0.38] and necrotising enterocolitis [40/351 (11.4%) vs. 32/359 (8.9%), P=0.32] between the two groups. The incidence of poor neurodevelopment after cesarean delivery was similar to that after vaginal delivery [105/351 (29.9) vs. 104/359 (29.0%), P=0.78].

Conclusions

In neither neurodevelopment nor neonatal mortality did cesarean birth offered significant advantages to VLBW infants. Moreover, the operation might be associated with an increased risk of respiratory distress syndrome for VLBW infants. The mode of delivery of VLBW infants should be largely based on obstetric indications and maternal considerations rather than perceived better outcomes for the neonate.     

Budd-Chiari syndrome

Badd-Chiari syndrome (BCS) is a rare disorder clinically characterised by pain abdomen, hepatomegaly and ascites. We observed 3 children with BCS. Histopathology of biopsy specimen of liver was diagnostic. One child had developed cirrhosis of liver because of long standing venous congestion. Inferior vena cavography (IVC-graphy) and percutaneous hepatography were helpful to localise the site and extent of obstruction. The cause of occulsion of hepatic vein (HV) and inferior vena cava (IVC) could not be identified. One child showed spontaneous improvement. Other two children had progressive disease. Early recognition of the syndrome can help the patient, in presence of operable causes.     

GATA3 mutation in a family with hypoparathyroidism,deafness and renal dysplasia syndrome

Background

The hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by GATA3 gene mutation. We report here a case that both of a Chinese boy and his father had HDR syndrome which caused by a novel mutation of GATA3.

Methods

Polymerase chain reaction and DNA sequencing was performed to detect the exons of the GATA3 gene for mutation analysis.

Results

Sequence analysis of GATA3 revealed a heterozygous nonsense mutation in this family: a mutation of GATA3 at exon 2 (c.515C >A) that resulted in a premature stop at codon 172 (p.S172X) with a loss of two zinc finger domains.

Conclusion

We identified a novel nonsense mutation which will expand the spectrum of HDR-associated GATA3 mutations.     

Histiocytosis X

Histiocytosis X is a spectrum of diseases which should be classified among the wide spectrum of histiocytic disorders, consisting of proliferation of the Mononuclear Phagocyte System (MPS). The clinical manifestations reflect the site of histiocytic proliferation and may vary from a solitary bone lesion discovered by chance on X-ray film to a disease with a rapidly fatal course affecting almost any organ. The classic classification into eosinophilic granuloma of bone, Hand-Schüller-Christian disease and Letterer-Siwe disease and other related classifications fail to demonstrate the variable course and the smooth transitions, and do not correlate with the histologic findings and prognosis. The features of the immature and mature macrophage and, in this connection, the histologic findings of non-cutaneous material and the histochemical studies allow a classification into:

1. Benign Histiocytosis X
2. Solitary or multiple bone lesions
3. Benign disseminated Histiocytosis X
4. Malignant Histiocytosis X.

The clinical manifestations themselves do not allow a distinction to be made between the two entities, but the latter may lead to severe dysfunction of certain organs. A survey of the clinical manifestations is given. Benign Histiocytosis X comprises a widely variable spectrum, ranging from a solitary bone lesion to disseminated disease, but mostly with favourable outcome; malignant Histiocytosis X has a uniform, rapidly fatal, acute course with severe dysfunction of organs. This classification is highly correlated with prognosis, which is based on histology, age at onset, dysfunction of liver, lung and hemopoietic system, and a score system. In differential diagnosis, malignant Histiocytosis X must be distinguished from other histiocytic disorders and combined immunodeficiency, which have very similar symptomatology, but often have a recessive inheritance. The etiology of Histiocytosis X is still unknown, but histochemical and electronmicroscopic studies point to a response of mature and immature histiocytes to an unidentified antigen. Treatment of bone lesions consists in curettage or irradiation (600–1000 rads), if the lesions give rise to symptoms. Relapses are frequent. In benign disseminated Histiocytosis X a treatment protocol similar to that of acute lymphoblastic leukemia (ALL) is proposed and a more intensive protocol in malignant Histiocytosis X. The prognosis of Histiocytosis X has substantially improved with the advent of multiple cytostatic treatment. Histiocytosis X is a spectrum of diseases of unknown etiology, consisting in a proliferation of differentiated cells of the Mononuclear Phagocyte System (MPS), known as histiocytes. The clinical manifestations are widely variable, mirroring the widespread distribution of the MPS, affecting almost any organ. As a result there are numerous smooth transitions between the three classical entities distinguished in the literature: eosinophilic granuloma, Hand-Schüller-Christian disease and Letterer-Siwe disease. Because of the variable course of Histiocytosis X, and for prognostic and therapeutic reasons, a classification based on clinical and histologic manifestations is desirable. The purpose of this report is to review the literature concerning the classification of histiocytic disorders and Histiocytosis X. On the basis of the clinical manifestations, their prognostic value and the histologic findings, a classification (Table 1) is given that will be relatively simple to use in practice as a guide to prognosis and therapy.     

Cellular reaction to Pneumocystis carinii

Two types of Pneumocystis carinii infections must be distinguished:

1. Interstitial plasmacell pneumonia, which occurs only in premature or in marasmic infants between the 10th and 24th week of life. It is most frequently associated with severe diarrhoea, atrophy of the bowel mucosa and IgG levels of below 200 mg%. Pneumocystis carinii organisms spread rapidly throughout the alveoli of all pulmonary lobes in these debilitated infants. The capsular antigen of the Pneumocystis carinii cysts elicits a massive plasmacell infiltration of the alveolar septa, which is accompanied by immuneglobulin production of IgM type. This reaction occurs within 24 to 48 hrs and leads frequently to death. Morphometric counts on 65 cases showed that up to 78% of the entire lung space was formed by septa distended with plasmacells and proplasmacells. The organisms disappear from the alveoli within 2 to 3 days due to the hosts IgM antibody response. The cellular infiltrate persists and may in itself cause suffocation. Complete clearing of the interstitial infiltrate takes 6–8 weeks. This sudden massive infiltration of the entire lung does not occur in all cases. Pneumocystis carinii organisms occur frequently in the subpleural posterior alveoli, eliciting a minor focal interstitial plasmacell response, which remains clinically undetected.
2. Hypoergic Pneumocystosis may occur at any age and is associated with congenital immunedeficiency diseases, diseases of the reticulo-endothelial system and immunosuppressive therapy leading to IgG deficiency. No host response to the organism occurs under these circumstances. Morphometric counts on 51 human lungs showed no interstitial inflammatory infiltrate. The septa may occasionally be distended by neoplastic infiltrates of reticulo-endothelial type as for instance in plasmacell myeloma, lymphoma or leukaemia, which is the cause rather than the result of the Pneumocystosis.

     

Treatment of cryptorchidism by intranasal synthetic LH-RH and its analogue d-ser(TBU)6-LHRH-EA10

Sixty-seven prepubertal boys with either uni- or bilateral cryptorchidism were treated with LH-RH or its analogue Hoe 766. In all cases the undescended testes were located in the inguinal canal; none had retractile testes.

1. 23 boys were given 200 μg LH-RH-6 times daily for 7 days
2. 24 boys were given 500 μg LH-RH-2 times daily for 7 days
3. 10 boys received 100 μg Hoe 766 every other day at 8 p.m. for a total of 8 insufflations
4. 10 boys received 25 μg Hoe 766 every other day at 8 p.m. for a total of 8 insufflations.

The treatment was performed with control by LH-RH tests and testing the pituitary reserve of gonadotropins. Plasma testosterone was measured by RIA. Of the 47 boys treated with synthetic LH-RH, 14 (29.8%) gave a positive response with descent of the testes into the scrotum (A: 21.7%; B: 37.5%). The basal values and the pituitary reserves of LH and FSH did not change after therapy. Plasma testosterone showed an increase in the whole group of patients. Hoe 766 caused an increase in the FSH in all boys, but the curve was significantly higher in group C. There was no difference in plasma testosterone level between group C and D. None of the ten patients in group C responded to the therapy. In three patients of group D (30%) both testes descended. The administration of hCG to those boys who had not responded to the synthetic LH-RH or its analogue therapy led to the descent of three testes in group A and B, of two testes in group C, and of three testes in group D. Treatment of crytorchidism by synthetic LH-RH or its analogue Hoe 766 for a short time can produce good results. The dosage of the drugs plays an important role in determining its effect. No change was found in gonadotropin secretion induced by synthetic LH-RH nasal spray therapy. The effect of intranasal administration of Hoe 766 is dose-dependent for FSH, but not for LH. When using synthetic LH-RH the best results were obtained by other authors with treatment of at least four weeks. The best results with synthetic or analogue LH-RH treatment were obtained in those subjects whose testes were located closer to the external ring. No side effects were observed either during or after the treatment.     

A prospective pilot study: Can the biliary tree be visualized in children younger than 3 months on Magnetic Resonance Cholangiopancreatography?

Background

Magnetic resonance cholangiopancreatography (MRCP) could aid in the diagnosis of biliary atresia, a hepatic pathology with thin, irregular or interrupted biliary ducts. There is little published evidence of MRCP appearances in normal neonates and young infants.

Objective

To assess the use of MR cholangiopancreatography in visualizing the biliary tree in neonates and infants younger than 3 months with no hepatobiliary disorder, and to assess this visibility in relationship to the child’s age, weight, and sedation and fasting states.

Materials and methods

Between December 2008 and October 2010 our department performed MRI of the brain, orbits and face on 16 full-term neonates and infants. Each child was younger than 3 months (90 days) and without any hepatobiliary disorders. The children were scanned with a respiratory-gated 0.54?×?0.51?×?0.4-mm³ 3-D MRCP sequence. We used a reading grid to assess subjectively the visibility of the extrahepatic bile ducts along with extrahepatic bile duct confluence. The visibility of the extrahepatic bile duct confluence was assessed against age, weight, and sedation and fasting states.

Results

The extrahepatic bile duct confluence was seen in 10 children out of 16 (62.5%). In the neonate sub-group (corrected age younger than 30 days), the MRCP was technically workable and the extrahepatic bile duct confluence was seen in four cases out of eight (50%). This visualization was up to 75% in the subgroup older than 30 days. However, statistically there was no significant difference in visibility of the extrahepatic bile duct confluence in relationship to age, weight or MRCP performance conditions (feeding, fasting or sedation).

Conclusion

The complete normal biliary system (extrahepatic bile duct confluence included) is not consistently visualized in infants younger than 3 months old on non-enhanced MRCP. Thus the use of MRCP to exclude a diagnosis of biliary atresia is compromised at optimal time of surgery.     

Prognostic factors of gastroesophageal reflux disease in congenital diaphragmatic hernia: a multicenter study

Purpose

Gastroesophageal reflux disease (GERD) is one of the concomitant problems in infants with congenital diaphragmatic hernia (CDH). We assessed risk factors of GERD in CDH patients.

Methods

The retrospective observational study for CDH infants was conducted. Cases of CDH who were born between January 2006 and December 2010, were operated in the 9 participating institutions, and survived to discharge were included. Completion of medical therapy for GERD and incidence of surgery were primary outcomes. Kaplan–Meier survival analysis and Cox proportional hazards regression were used.

Results

In 182 cases of CDH, the medical therapies for GERD were performed in 23.8 % (40/168), and were completed in 60.0 % (24/40). Prenatal detection of CDH (HR 5.87, CI 1.6–18.8, p = 0.012) and tube feeding at discharge (HR 5.04, 95 % CI 1.3–33.1, p = 0.016) were significantly correlated with unsuccessful weaning from medical therapy. Surgery for GERD was performed in 10.7 % (18/169). Gestational age (HR 4.78, 95 % CI 1.5–21.1, p = 0.006) and diaphragmatic defect of more than 75 % (HR 4.3, 95 % CI 1.6–12.9, p = 0.005) were significantly correlated with need for antireflux surgery.

Conclusion

Diaphragmatic defect of more than 75 % was risk factor of future need for antireflux surgery.     

Recurrent episodes of testicular swelling preceding Henoch-Schönlein purpura by 11 months

We report an unusual presentation of Henoch-Schönlein purpura in a 4-year-old boy. He presented with two isolated episodes of tender testicular swelling, and 11 months after the first episode developed a full blown picture of Henoch-Schönlein purpura accompanied by orchitis. A latent period of orchitis preceding Henoch-Schönlein purpura of this duration has not been described previously and its clinical implications are discussed.     

Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats

Purpose

The use of dexamethasone (Dx) stimulates growth, fetal lung maturation and can improve pulmonary hypertension in congenital diaphragmatic hernia (CDH). Our aim was to evaluate the effect of Dx on the lung after fetal pulmonary ventilation in the CDH rat model.

Methods

Some groups underwent prenatal treatment with dexamethasone (0.4 mg/kg) that was given at 18.5 gestational day (GD). Sprague–Dawley rat fetuses were divided into groups: control (C); ventilated control (CV); control exposed to dexamethasone (CDx); ventilated control exposed to dexamethasone (CVDx); congenital diaphragmatic hernia (CDH), ventilated CDH (CDHV), CDH exposed to dexamethasone (CDHDx) and ventilated CDH exposed to dexamethasone (CDHVDx). At 21.5 GD fetuses were delivered by C-section, weighed and ventilated for 30 min. We analyzed the lung morphometry by Masson’s Trichrome stain, and VEGF, VEGFR1, VEGFR2 and NOS3 expression by immunohistochemistry.

Results

All fetuses with CDH, with or without prenatal dexamethasone showed lung and body weight lower than control fetuses (p < 0.05). All groups that received dexamethasone showed a decrease in the medial muscular layer of arterioles, the internal diameter of the air spaces (Lma) and length of parenchymal transection/airspace ratio (p < 0.05). In the immunohistochemistry, VEGF decreased more in CDHDV group (p < 0.05). VEGFR1 showed no difference, whereas VEGFR2 decreased significantly in the CDHDV group (p < 0.05). NOS3 increased in the group CDHDV (p < 0.05).

Conclusion

The use of prenatal dexamethasone added to ventilation alters the VEGF and NO pathways.     

Cerebrospinal fluid concentration and urinary excretion of cyclic adenosine-3′, 5′-monophosphate in various diseases of children

Cerebrospinal fluid (CSF) concentration and urinary excretion of cyclic adenosine-3′,5′-monophosphate (cAMP) were measured in children aged from 3 days to 15 years by the protein-binding method of Gilman (1970). The mean CSF cAMP concentration (22.4±0.6 (S.E.) nmol/l) of 24 “healthy” children tended to be lower (P<0.2) than that of adult patients who revealed no pathological findings on clinical examination. No difference in the results was found between the sexes. High cAMP concentrations were found in CSF of children suffering from cerebellar glioma, hypothalamic precocious puberty, bacterial meningitis, or Cushing's disease. The urinary excretion of cAMP varied from 0.2 to 5.3 in “healthy” and from 1.3 to 7.6 μmol/24 hrs in diseased children. Two children with pheochromocytoma showed a striking decrease in the rate of urinary excretion of the nucleotide after surgical treatment.     

Strain measurement by cardiovascular magnetic resonance in pediatric cancer survivors: validation of feature tracking against harmonic phase imaging

Background

Left ventricular strain may be a more sensitive marker of left ventricular dysfunction than ejection fraction in pediatric cancer survivors after anthracycline therapy, but there is limited validation of strain measurement by feature tracking on cardiovascular magnetic resonance (MR) images.

Objective

To compare left ventricular circumferential and radial strain by feature tracking vs. harmonic phase imaging analysis (HARP) in pediatric cancer survivors.

Materials and methods

Twenty-six patients (20.2?±?5.6 years old) underwent cardiovascular MR at least 5 years after completing anthracycline therapy. Circumferential and radial strain were measured at the base, midventricle and apex from short-axis myocardial tagged images by HARP, and from steady-state free precession images by feature tracking.

Results

Left ventricular ejection fraction more closely correlated with global circumferential strain by feature tracking (r?=??0.63, P?=?0.0005) than by HARP (r?=??0.39, P?=?0.05). Midventricular circumferential strain did not significantly differ by feature tracking or HARP (?20.8?±?3.4 vs. ?19.5?±?2.5, P?=?0.07), with acceptable limits of agreement. Midventricular circumferential strain by feature tracking strongly correlated with global circumferential strain by feature tracking (r?=?0.87, P?HARP, particularly at higher values of radial strain. Intraobserver and interobserver reproducibility was excellent for feature tracking circumferential strain, but reproducibility was poor for feature tracking radial strain.

Conclusion

Midventricular circumferential strain by feature tracking is a reliable and reproducible measure of myocardial deformation in patients status post anthracycline therapy, while radial strain measurements are unreliable. Further studies are necessary to evaluate potential relation to long-term outcomes.