Postprandial lipid absorption in seven heterozygous carriers of deleterious variants of MTTP in two abetalipoproteinemic families.

BACKGROUND: Abetalipoproteinemia, a recessive disease resulting from deleterious variants in MTTP (microsomal triglyceride transfer protein), is characterized by undetectable concentrations of apolipoprotein B, extremely low levels of low-density lipoprotein cholesterol in the plasma, and a total inability to export apolipoprotein B-containing lipoproteins from both the intestine and the liver. OBJECTIVE: To study lipid absorption after a fat load and liver function in 7 heterozygous relatives from 2 abetalipoproteinemic families, 1 previously unreported. RESULTS: Both patients are compound heterozygotes for p.(Arg540His) and either c.708_709del p.(His236Glnfs*11) or c.1344+3_1344+6del on the MTTP gene. The previously undescribed patient has been followed for 22 years with ultrastructure analyses of both the intestine and the liver. In these 2 families, 5 relatives were heterozygous for p.(Arg540His), 1 for p.(His236Glnfs*11) and 1 for c.1344+3_1344+6del. In 4 heterozygous relatives, the lipid absorption was normal independent of the MTTP variant. In contrast, in 3 of them, the increase in triglyceride levels after fat load was abnormal. These subjects were additionally heterozygous carriers of Asp2213 APOB in-frame deletion, near the cytidine mRNA editing site, which is essential for intestinal apoB48 production. Liver function appeared to be normal in all the heterozygotes except for one who exhibited liver steatosis for unexplained reasons. CONCLUSION: Our study suggests that a single copy of the MTTP gene may be sufficient for human normal lipid absorption, except when associated with an additional APOB gene alteration. The hepatic steatosis reported in 1 patient emphasizes the need for liver function tests in all heterozygotes until the level of risk is established.

Cervical bronchogenic cysts: usual and unusual clinical presentations.

OBJECTIVE: To discuss the clinical, radiologic, and histopathologic characteristics of cervical bronchogenic cysts. DESIGN: Retrospective case study using a pathologic database at our institution. SETTING: Pediatric hospital. PATIENTS: Eight patients with cervical bronchogenic cysts were identified in the past 13 years (January 1994 to December 2007). MAIN OUTCOME MEASURES: The patients' clinical presentations and surgical procedures are described. RESULTS: Two cervical bronchogenic cysts were located on the cervical anterior midline, 5 were anterolateral suprasternal, and the other was paraspinal. One corresponded to an intralaryngeal and extralaryngeal cyst. One was associated with an ectopic thymus. No patient had been diagnosed as having a bronchogenic cyst before surgery. No major surgical complications were noted. There was no relapse after surgery. CONCLUSIONS: Although rare, cervical bronchogenic cysts are difficult to differentiate clinically from other cystic cervical masses because their location, radiologic characteristics, and evolution can mimic those of any other cervical mass. Cervical cysts are usually a pathologic finding, showing respiratory-type epithelium, cartilage, mucinous glands, and smooth muscle fibers. They result from abnormal development of the tracheobronchial tree. Some atypical locations or associations may be explained by embryologic origin. The curative treatment consists of complete surgical resection. To our knowledge, this study represents the largest pediatric series published about cervical bronchogenic cysts.

Molecular diagnosis of Saksenaea vasiformis cutaneous infection after scorpion sting in an immunocompetent adolescent.

We report the first case of cutaneous mucormycosis after a scorpion sting in Tunisia. Histopathology showed broad aseptate hyphae suggestive of a Zygomycete. Saksenaea vasiformis was identified by PCR amplification and sequencing of the fungal DNA on a cutaneous biopsy. Successful treatment was obtained by surgery and liposomal amphotericin B.

[Hamartoma of the spleen (splenoma) in a child with sickle cell anemia]. / Hamartome de la rate (splénome) chez un enfant drépanocytaire.

Hamartomas of the spleen or splenomas are uncommon benign lesions that predominantly occur in adults. We report a case of an 11-year-old girl with sickle cell anemia who had a single splenic 1.8 cm nodule incidentally found during splenectomy and histologically characterized by disorganized red pulp tissue without interspersed white pulp leading to the diagnosis of hamartoma. The association of hamartoma and hematological conditions is a very unusual condition in children.

Neuropathic visceral dysmotility, brain cysts and calcifications, facial dysmorphism and developmental delay in two sibs. A new syndrome?

Syndromes with smooth muscle dysmotility are uncommon, and may be related either to smooth muscle myopathy, or to neuropathy. In most instances, neuropathic visceral dysmotility is an isolated finding leading to chronic intestinal pseudo-obstruction syndrome (CIPO). We report here on two sibs, born to consanguineous parents, with neuropathic visceral dysmotility and CNS anomalies. They share facial dysmorphia, neurogenic megacystis, intracerebral calcifications, and developmental delay. The elder one, a girl, has microcephaly and multicystic kidneys, and her brother has a more extensive neuropathic visceral disorder leading clinically to CIPO. CIPO associated with megacystis is relatively frequent but is rarely associated with mental retardation. The cases reported in the literature are different from those described here, clinically and histologically. A recessively inherited form of CIPO associated with widespread intra-cerebral calcifications, malabsorption is known as Cockel syndrome. Severity of Cockel syndrome, absence of urinary tract involvement and neuropathologic discrepancies allow distinction with the disorder reported here. In conclusion, the two siblings described here have facial dysmorphia, vesical and (in one of them) intestinal neurogenic dysmotility, intracerebral calcifications and developmental delay that could represent a specific, recessively inherited form of CIPO.

Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the neonatal period and is characterized by persistent pulmonary hypertension of the newborn (PPHN) and pulmonary hypoplasia. Endothelin-1 (ET-1) dysregulation may play a significant role in the pathophysiology of PPHN and ET-1 acts through binding to type A (ETA) and type B (ETB) receptors. Therefore, ETA and ETB receptor protein expression was studied using immunohistochemistry in 10 lung specimens obtained from newborns with CDH, and 4 normal lung specimens, in order to explore whether dysregulation of ETA and ETB expression contributes to PPHN. ETA and ETB mRNAs were then quantified using real-time RT-PCR in laser-microdissected pulmonary resistive arteries. In the lungs of newborns with CDH, immunohistochemistry of both ETA and ETB receptors demonstrated over-expression in the thickened media of pulmonary arteries. Using laser microdissection and real-time RT-PCR, higher levels of ETA and ETB mRNA were found in CDH pulmonary arteries than in controls: this increase was more pronounced for ETA mRNA. This study provides the first demonstration of ET-1 receptor dysregulation in association with structural alteration of pulmonary arteries in newborns with CDH and PPHN. This dysregulation preferentially affects the ETA receptor. These results suggest that dysregulation of ET-1 receptors may contribute to PPHN associated with CDH.

Neonatal exposure to 65% oxygen durably impairs lung architecture and breathing pattern in adult mice.

STUDY OBJECTIVE: To test the hypothesis that exposure to hyperoxia during the postnatal period of rapid alveolar multiplication by septation would cause permanent impairments, even with moderate levels of hyperoxia. DESIGN: We exposed mouse pups to 65% O(2) (hyperoxic mice) or normoxia (normoxic mice) during their first postnatal month, and we analyzed lung histology, pulmonary mechanics, blood gas, and breathing pattern during normoxia or in response to chemical stimuli in adulthood, when they reached 7 to 8 months of postnatal age. RESULTS: Hyperoxic mice had fewer and larger alveoli than normoxic mice (number of alveoli per unit surface area of parenchyma, 266 +/- 62/mm(2) vs 578 +/- 77/mm(2), p < 0.0001) [mean +/- SD], the cause being impaired alveolarization (radial alveolar count, 5.8 +/- 0.2 in hyperoxic mice vs 10.5 +/- 0.5 in normoxic mice, p < 0.0001). Respiratory system compliance was higher in hyperoxic mice (0.098 +/- 0.006 mL/cm H(2)O) than in normoxic mice (0.064 +/- 0.006 mL/cm H(2)O, p < 0.016). Baseline tidal volume (VT) and breath duration (TTOT]) measured noninvasively by whole-body plethysmography were larger in hyperoxic mice than in normoxic mice (VT, + 15%, p < 0.01; TTOT, + 12%, p < 0.01). Despite these impairments, blood gas, baseline minute ventilation E, and E responses to hypoxia and hypercapnia were normal in hyperoxic mice, compared with normoxic mice. CONCLUSION: Hyperoxic exposure during lung septation in mice may cause irreversible lung injury and breathing pattern abnormalities in adulthood at O(2) concentrations lower than previously thought. However, ventilatory function and body growth were preserved, and ventilatory function showed no major abnormalities, at least at rest, despite early oxygen-induced injuries.