Type 2B von Willebrand Disease: Early Manifestation as Neonatal Thrombocytopenia.

Here, we report about a preterm female newborn with a prolonged course of severe thrombocytopenia and hematomas. The family history was positive for von Willebrand disease type 2B (VWD 2B). Diagnosis of VWD 2B was identified analyzing von Willebrand factor (VWF) parameters (VWF:antigen, VWF:activity, VWF multimer analyses) and performing light transmission aggregometry (with half concentration of ristocetin). In addition, the diagnosis was confirmed by molecular genetic analysis: identification of a disease-causing missense mutation (Val1316Met) in the VWF gene associated with a severe course of VWD 2B, which had been previously reported. Treatment with a VWF-containing plasma concentrate was initiated. Because the combination of prematurity and very low platelet count is often associated with intracranial bleeding, at the beginning platelet concentrates were transfused. Fortunately, the patient did not develop serious bleeding episodes. Interestingly, the patient had a mutation in the VWF gene, which had been described to be associated with aggravation of thrombocytopenia especially in stressful situations. Therefore, we replaced venous blood withdrawals by capillary blood samplings when possible and, consequently, we observed an increase of the platelet count after this change in management. At the age of 2 months, the patient was discharged after stabilization of the platelet count without any bleeding signs and without a need of long-term medication.

Cystic Encephalomalacia following Vasculopathy and Vasospasm of Proximal Intracranial Arteries Due to Pneumococcal Meningitis in a Infant.

Despite the availability of modern antibiotics, pneumococcal meningitis in both children and adults remains a severe disease-one known to frequently cause grave complications and residual disability. Although the appearance of arterial vasospasms in bacterial meningitis systematically has been investigated and reported on for adult patients, such research is lacking when it comes to infants. We report on a 4-week-old infant who, 6 days after onset of pneumococcal meningitis, suffered severe neurological deterioration with treatment-resistant seizures and coma. Generalized cortical and subcortical edema developed in conjunction with diminished cerebral blood flow, as depicted in magnetic resonance angiography and serial Doppler-sonographic examinations. The ischemia resulted in extensive cystic encephalomalacia. We propose that the degree of variation in cerebral blood flow in the acute phase was the result of an extensive arterial vasculopathy involving vasospasms. Awareness of this complication and prospective serial Doppler-sonographic examinations may improve our understanding of the connection between brain edema and vasculopathy. At present, however, no effective treatment appears available.

Selective unilateral lung ventilation in preterm infants with acquired bullous emphysema: a series of nine cases.

BACKGROUND AND AIMS: Immature lungs of preterm infants are particularly prone to overdistension from mechanical ventilation or continuous positive airway pressure. In these infants a localized pulmonary emphysema (PE) can develop. Conventional therapy regimens to resolve this process sometimes fail and especially in the case of bullous emphysema (BE) invasive procedures such as surgical resection of the affected lobe ultimately may be required. In the past few years we have applied selective one-sided lung ventilation, a nearly forgotten therapeutic option, in these infants with acquired BE. METHODS: Medical charts of preterm infants in two Divisions of Neonatology, born between 1993 and 2010 with acquired BE treated with selective one-sided ventilation were reviewed. Gestational age, clinical presentation, course of disease, associated treatment, duration of ventilation and outcome of one-sided lung ventilation are recorded. Therapy was deemed successful if thereafter chest X-ray showed a permanent resolution of the BE and, in case of BPD, lung appearance was comparable to a grade < III according to Weinstein [Weinstein et al. Pediatr Pulmonol 1994; 18: 284-289]. RESULTS: Overall, nine preterm infants with a gestational age between 24 and 35 weeks and a birth weight between 500 and 3,170 g underwent one-sided lung ventilation. This intervention was started between day 12 and day 35 after birth and was continued for 24 hr to 7 days. In three cases selective intubation was performed on the left side. Two patients needed a second course of one-sided ventilation and one had three courses. Therapy was successful in seven patients, who had no recurrence of BE. CONCLUSIONS: Selective one-sided intubation is technically challenging, in particular for the left bronchus, but seems to be feasible and helpful. If during selective intubation the affected lung lobe shows complete atelectasis for more than 48 hr the overdistension of airways probably will permanently resolve.

Exposure to furosemide as the strongest risk factor for nephrocalcinosis in preterm infants.

BACKGROUND: The objective of this study was to determine which of the many risk factors for nephrocalcinosis (NC) in preterm infants are most relevant. METHODS: In 55 neonates born before 32 completed weeks of gestation, parameters relevant to NC were analyzed. Median birthweight was 1010 g (range 500-2070 g). Fifteen (27%) asymptomatic children had ultrasonographic NC. RESULTS: In multivariate analysis the strongest independent risk factor was furosemide therapy above 10 mg per kg bodyweight cumulative dose, with a 48-fold increased risk of NC (odds ratio confidence interval 4.0-585, P < 0.01). The risk of NC was 1.65-fold higher per 100 g lower weight (1.07-2.56, P= 0.02) and 4.5-fold higher per mmol/l of urinary calcium concentration (1.14-17.7, P= 0.03). Many other risk factors were only significant in univariate analysis (gestational age, mechanical ventilation, infection, broncho-pulmonary dysplasia, blood transfusions, intraventricular hemorrhage, surfactant therapy, vasopressors, phenobarbital or caffeine, duration of hospital stay), indicating an indirect effect only. Other parameters of calcium and phosphate homeostasis were not significant, possibly due to standardized supplementation. CONCLUSION: We suggest that in preterm infants, furosemide should be prescribed with caution and close monitoring of calcium excretions is advisable. Some guidelines for infant respiratory distress syndrome now favor calcium-sparing thiazides if diuretics are considered.

Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene.

Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from mutations inactivating ADAMTS-2, an enzyme excising the aminopropeptide of procollagens type I, II, and III. All previously described mutations create premature stop codons leading to a marked reduction in the level of mRNA. In this study, we analyzed the ADAMTS2 cDNA sequences from five patients displaying clinical and/or biochemical features consistent with a diagnosis of either typical or potentially mild form of EDS type VIIC. Three different alterations were detected in the two patients with typical EDS type VIIC. The first patient was homozygous for a genomic deletion causing an in-frame skipping of exons 3-5 in the transcript. In the second patient, the allele inherited from the mother lacks exon 3, generating a premature stop codon, whereas the paternal allele has a genomic deletion resulting in an in-frame skipping of exons 14-16 at the mRNA level. Although the exons 3-5 or 14-16 encode protein domains that have not been previously recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired in vitro and in vivo, providing evidence for the requirement of these domains for proper enzyme function. The three other patients with a phenotype with some resemblance to EDS type VIIC only had silent and functionally neutral variations also frequently found in a normal population.

The natural history, including orofacial features of three patients with Ehlers-Danlos syndrome, dermatosparaxis type (EDS type VIIC).

Ehlers-Danlos syndrome (EDS) dermatosparaxis type (type VIIC) and the related disease of cattle dermatosparaxis, are recessively inherited connective tissue disorders, caused by a deficient activity of procollagen I N-proteinase, the enzyme that excises the N-terminal propeptide in procollagen type I, type II, and type III. Although well documented in cattle, to date only seven human cases have been recorded, most of them aged under 2 years. We document the natural history of three patients with EDS dermatosparaxis type, two of whom have been reported before the age of 2 years, and one new patient. The phenotype of the patients, and especially the facial resemblance, is striking, making this a clinically recognizable condition. The most consistent anomalies during the first years of life are premature rupture of the membranes, extreme skin fragility and easy bruising, large fontanels, blue sclerae, puffy eyelids, micrognathia, umbilical hernia, and short fingers. Joint hypermobility becomes more important with age. The children are at risk for rupture of internal organs due to soft tissue fragility, as is illustrated by different internal events in two of the three patients described here. Orofacial features include micrognathia, a frontal open bite, and gingival hyperplasia with varying degrees of hyperkeratosis. The deciduous dentition shows abnormal morphology of the molars, obliteration of the tooth pulp, and severe enamel attrition. The permanent dentition shows agenesis and microdontia of several teeth. Tooth discoloration, dysplastic roots, and tooth pulp obliteration are present in a restricted number of permanent teeth.

Recurrent attacks of fear and visual hallucinations in a child.

The case of a 7-year-old boy suffering from recurrent nocturnal and occasional daytime attacks with intense fear and complex visual hallucinations is presented. His state was otherwise normal, as were routine electroencephalographic (EEG) and magnetic resonance imaging (MRI) investigations in the past. Several differential diagnoses such as panic disorder, pavor nocturnus, and nightmares were considered but could not be definitely established or excluded. Since the attacks appeared after the divorce of his parents, an adjustment disorder was suspected, and the patient received psychotherapy for more than 2 years without an effect on the attacks. Only when long-term video-EEG recorded two typical attacks with left temporal ictal seizure patterns was focal epilepsy diagnosed and successfully treated with antiepileptic medication. A suspected origin of seizures in the amygdala was supported by a high-resolution MRI showing a cortical dysplasia extending from the left anteromedial temporal lobe to the amygdala. The case exemplifies difficulties in the differential diagnosis of panic-like attacks and underlines the value of long-term video-EEG, which may be necessary to establish the correct diagnosis and to prevent ineffective therapeutical approaches.