Agenesis of the internal carotid artery: a family pathology?

The internal carotid artery agenesis is a rare malformation disorder. We report the case of a 12-year-old boy suffering migraine, who had presented an episode featuring amaurosis fugax, spontaneously regressed. CT angiography images show hypoplasia of the left common carotid artery with loss of opacification of the left internal carotid artery consistent to agenesis. Moreover CT scans through the skull base demonstrate absence of left petrous carotid canal and an hypertrophic left middle cerebral artery originating from an aberrant artery arising from the right cavernous carotid. All diagnostic examinations confirmed the presence of the internal carotid artery agenesis, as Lie's type IV. We started an annual follow up that over the next 7 years did not reveal any change in magnetic resonance angiography images.

Reliability of vertebral fractures assessment (VFA) in children with osteogenesis imperfecta.

The aim of this study is to evaluate the diagnostic accuracy of vertebral fractures assessment (VFA) in comparison with conventional radiography in identifying vertebral fractures in children and adolescents affected by OI. On 58 patients (33 males, 25 females; age range 1-18 years; 41 children and 17 adolescents) with osteogenesis imperfecta (OI type I, n = 44, OI type III, n = 4; OI type IV, n = 10), lateral spine images by radiographs and by dual-energy X-ray absorptiometry (DXA) were acquired. For vertebral fracture diagnosis, plain radiographs were used as "gold standard" and VFA and morphometric X-ray absorptiometry (MXA) were performed. The visualized vertebrae were 738 (97.9%) by radiographs and 685 (90.9%) by DXA of a total of 754 vertebrae from T4 to L4. VFA and MXA identified, respectively, 129 (74%) and 116 (66%) of the 175 vertebral fractures detected by radiographs. Radiographs identified 36 patients with vertebral fractures, VFA 35 and MXA 41 (6 false positives). On a per vertebra basis, radiographs and VFA had elevated agreement (93.9%; k score 0.81, 95% CI 0.76-0.86), that resulted slightly lower for MXA (90.6%; k score 0.72, 95% CI 0.65-0.78). VFA and MXA demonstrated high sensitivity (95.6 and 94.1 %, respectively) while specificity was 100% for VFA and 90.6% for MXA on a per patient basis; the agreement was excellent for VFA (98.3%; k score 0.96, 95% CI 0.89-1.03) and good for MXA (87.9%; k score 0.73, 95% CI 0.55-0.91). The diagnostic performance parameters resulted better for VFA (sensitivity 95.6%; specificity 100%; PPV 100%; NPV 97.2%), than for MXA (sensitivity 94.1%; specificity 85.4%; PPV 72.7%; NPV 97.2%). The results of our study demonstrate the reliability of VFA for diagnosis of vertebral fractures in children with OI suggesting its use as a more safe and practical alternative to conventional radiography.

Respiratory distress in newborn: evaluation of chest X-rays.

We discuss the anatomic and pathophysiological patterns of preterm and term newborn. Particular attention is directed to technical artefacts relating to the interpretation of chest radiography. We analyze the reading of chest X-Ray of preterm with low birth weight and poor lung maturation. Are also taken into account X-Ray features relating to alveolar "recruitment" and radiographic changes after surfactant's administration. We highlight the most important paintings of bruncopulmonary dysplasia and its evolution. The most frequent neonatal pulmonary inflammation and thoraco-pulmonary malformation, that may affect more the neonatologist, are mentioned. We discuss the new diagnostic approach with non invasive techniques (ultrasound) in the neonatal distress. Some easily recognizable congenital heart disease are finally describes.

Diamond-Blackfan anaemia in the Italian population.

Diamond-Blackfan anaemia (DBA) is a congenital disease characterized by defective erythroid progenitor maturation: 30% of patients have congenital malformations. The link between these malformations and defective erythropoiesis is unclear: a defect in a molecule acting both on embryo development and haemopoiesis has been proposed. Inheritance is autosomal dominant in most familial cases, but recessive families have also been reported. Many cases are sporadic. A DBA locus has been mapped on chromosome 19q13.2 (Gustavsson et al, 1997), but several families unlinked to this locus have also been reported (Gustavsson et al, 1998). This paper presents clinical, epidemiological and molecular data for DBA in the Italian population. Segregation analysis of 19q markers in patients with DBA showed exclusion of this locus in 5/12 families with inherited DBA. There was evidently locus heterogeneity for DBA in this population. A new microdeletion was identified in one patient. Other families, in which DBA segregates concordantly with the 19q critical region, suggest incomplete penetrance and expressivity of the DBA gene.

Long-term bone marrow cultures in Diamond-Blackfan anemia reveal a defect of both granulomacrophage and erythroid progenitors.

The hematopoietic defect of Diamond-Blackfan anemia (DBA) results in selective failure of erythropoiesis. Thus far, it is not known whether this defect originates from an intrinsic impediment of hematopoietic progenitors to move forward along the erythroid pathway or to the impaired capacity of the bone marrow (BM) microenvironment to support proliferation and differentiation of hematopoietic cells. Reduced longevity of long-term bone marrow cultures, the most physiologic in vitro system to study the interactions of hematopoietic progenitors and hematopoietic microenvironment, is consistent with a defect of an early hematopoietic progenitor in DBA. However, stromal adherent layers from DBA patients generated in a long-term culture system, the in vitro counterpart of BM microenvironment, did not show evidence of any morphologic, phenotypic, or functional abnormality. Our major finding was an impaired capacity of enriched CD34+ BM cell fraction from DBA patients, cultured in the presence of normal BM stromal cells, to proliferate and differentiate along the erythroid pathway. A similar impairment was observed in some DBA patients along the granulomacrophage pathway. Our result points to an intrinsic defect of a hematopoietic progenitor with bilineage potential that is earlier than previously suspected as a relevant pathogenetic mechanism of the disease. The finding of impaired granulopoiesis in some DBA patients underlines the heterogeneity of this rare disorder.

Mutational screening of thrombopoietin receptor gene (c-mpl) in patients with congenital thrombocytopenia and absent radii (TAR).

Thrombocytopenia with absent radii (TAR) is a rare autosomal recessive disease characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia. We performed mutational screening of coding and promoter regions of the c-mpl gene, encoding thrombopoietin (TPO) receptor, by sequence analysis in four unrelated patients affected by TAR syndrome. Our results indicate that c-mpl gene mutations are not a common cause of thrombocytopenia in TAR syndrome.

Familial idiopathic intracranial hypertension with spinal and radicular pain.

OBJECTIVE: To describe a mother and her 2 sons affected by idiopathic intracranial hypertension (IIH), associated in the sons with root irritation symptom. Unlike the other 4 families reported previously, obesity was not present in our patients. DESIGN: Case reports. SETTING: Department of pediatrics in a university school of Medicine, Naples, Italy. PATIENTS: A mother (aged 36 years) and her 2 sons (aged 14 and 9 years) developed IIH at different times. Neuroimaging showed an empty sella in the mother, while IIH was associated with spinal and radicular pain in her 2 sons. The mother and the younger son developed permanent visual loss. CONCLUSIONS: Ophthalmologic follow-up in our patients indicates that IIH is a chronic disease. Surgical treatment should be considered an option.

Variable response to the diepoxybutane test in two dizygotic twins with Fanconi's anemia and flow cytometry for diagnosis confirmation.

Fanconi's anemia (FA) is a rare, genetically heterogeneous, autosomal recessive disorder characterized by bone marrow failure, congenital abnormalities, chromosome instability, and increased susceptibility to neoplasia. Congenital abnormalities vary in location and in severity and not all patients are affected. Although the primary defect of FA is unknown, hypersensitivity to the clastogenic effect of agents that introduce cross-links in the DNA, such as diepoxybutane (DEB), is a marker of the FA phenotype in patients suffering from aplastic anemia without the physical characteristics of the syndrome and, conversely, in cases with abnormalities in the preanemic phase. We report the case of two dizygotic twins suffering from FA with discordant hematologic data. The DEB test repeated several times in various laboratories yielded conflicting results, whereas cell cycle studies by flow cytometry revealed a pattern typical of FA patients. Moreover, the flow cytometric pattern was correlated with the clinical severity of the disease.

Concealed administration of frusemide simulating Bartter syndrome in a 4.5-year-old boy.

A 4.5-year-old boy was admitted to three different hospitals because of a tendency towards dehydration and polyuria, along with normal blood pressure, hypochloraemia, hypokalaemia, metabolic alkalosis and an impaired urinary concentrating ability. A renal biopsy failed to reveal juxtaglomerular hyperplasia. The clinical and laboratory findings failed to improve despite supplementation with potassium chloride and treatment with indomethacin. The urine was found to contain frusemide. The parents denied any drug administration to the boy. The child is now doing well more than 1 year after separation from his mother. Since ingestion of diuretic cannot be differentiated from true Bartter syndrome by blood and urinary electrolyte measurements alone, a diuretic screen is warranted in children with findings consistent with Bartter syndrome.

Effect of interferon-alpha therapy in a patient with common variable immunodeficiency and chronic Epstein-Barr virus infection.

We report an 18-year-old boy with common variable immunodeficiency who presented with splenomegaly as well as left axillary and lateral cervical lymphadenopathy. Main laboratory investigations showed severe thrombocytopenia. Epstein-Barr virus (EBV) DNA was detected in the patient's throat-washing specimens and lymph node biopsy. Lymphocytes from the lymph node biopsy were also positive for EBV nuclear antigen. Serology for EBV and cytomegalovirus was negative. A therapeutic attempt with acyclovir did not influence the course of infection. Six months' treatment with human lymphoblastoid interferon-alpha (IFN alfa) brought about the normalization of clinical and hematologic conditions. Detection on throat-washing specimens carried out 1 year after therapy was negative. Our preliminary experience suggests that human lymphoblastoid IFN-alpha is a valid alternative in therapy of immunodeficient EB virus-infected patients.

Interferon alfa therapy in an infant with juvenile chronic myelogenous leukemia.

We describe an infant with juvenile chronic myelogenous leukemia (JCML), the diagnosis of which was made by the characteristic clinical and hematologic findings. The absence of a related HLA-compatible donor for bone marrow transplantation coupled with the awareness that chemotherapy is usually ineffective prompted our decision to treat the patient with lymphoblastoid interferon-alpha [alpha(Ly)-IFN]. During the 26-month course of treatment with alpha(Ly)-IFN an incomplete regression of hematologic and clinical findings was achieved. The above results, along with the easy administration and absence of considerable side effects, suggest that alpha(Ly)-IFN may be a useful therapeutic tool in patients affected by JCML awaiting bone marrow transplantation.

Six additional cases of the KBG syndrome: clinical reports and outline of the diagnostic criteria.

A diagnosis of KBG syndrome was made in six unrelated patients. They presented with slight mental retardation, macrodontia, and skeletal abnormalities. Microcephaly, short stature, facial anomalies, and syndactylies were also noted. The diagnostic criteria of the KBG syndrome are discussed.

Heterogeneity of the erythropoietic defect in two cases of Aase-Smith syndrome.

Here we report two children with Aase-Smith syndrome (triphalangeal thumbs and congenital red cell plasia). In vitro growth of erythroid colonies was normal in the first patient and totally absent in the other. In both patients, treatment with glucocorticoids induced remission of anemia. Our results suggest that the different growth patterns of erythroid colonies observed in the two patients could reflect the defect of erythroid differentiation occurring at discrete maturational levels.

Effect of measles-mumps-rubella vaccination on polymorphonuclear neutrophil functions in children.

Adherence, metabolic burst and chemotaxis of polymorphonuclear neutrophils (PMNs) were examined in 15 children before and seven days after measles-mumps-rubella vaccine administration. In all children, PMN functions were significantly reduced on the seventh day. Adherence, metabolic burst and chemotaxis tested in three subjects one month after vaccination had returned to normal values. Only two children presented transient hyperpyrexia. We conclude that measles-mumps-rubella vaccine administration suppresses PMN functions without clinical consequences. This is probably because attenuated strains of vaccine viruses do not replicate in lymphoid tissues as extensively as do wild-type strains.

Macroamylasemia in a 5-year-old girl.

In macroamylasemia, a macromolecular complex consisting of amylase linked to immunoglobulins circulates in the plasma and usually causes benign hyperamylasemia with low or normal amylasuria. Macroamylasemia is extremely rare in pediatric patients as it has been described in only four patients. We report herein the case of a 5-year-old girl with abdominal pain and macroamylasemia. To recognize macroamylase, we used agar gel electrophoresis, PEG precipitation, and fast protein liquid chromatography (FPLC). In our case, FPLC was found to be the most reliable method for the identification of the macromolecular complex. Macroamylasemia is merely a biochemical abnormality that is not associated with any kind of pathology. Its identification is therefore essential in order to avoid a wrong diagnosis, i.e., pancreatitis, with consequent inappropriate therapies.

Decreased adherence of polymorphonuclear neutrophils in children with viral infection.

The adherence of polymorphonuclear neutrophils was examined in 16 children affected by enteritis, pneumonia, hepatitis and infectious mononucleosis. The results were compared with those obtained in 30 healthy adult volunteers and in 15 healthy children of the same age. Adhesiveness was significantly higher in adults than in healthy children, and significantly higher in healthy children than in children with viral infection. In 7 patients tested one month after regression of the disorder, PMN adhesiveness had returned to normal.