Patients with mitochondrial respiratory-chain defects frequently exhibit lactic acidosis, ragged red fibers in skeletal muscle samples, and abnormal enzyme assays for the respiratory-chain complex. However, ragged red fibers and lactic acidosis are not always seen in all patients with mitochondrial respiratory-chain defects. We have encountered six children with biochemically proven respiratory chain defects, but typical ragged red fibers were not found in all six patients, and only five patients had increased serum lactate levels. Initially, they present with nonspecific features. However, persistent or progressive clinical features or multiple organ involvement eventually led to the diagnosis of respiratory-chain defects in these patients. Mitochondrial respiratory-chain defects should be considered in the differential diagnosis when persistent, progressive features and especially multiple organ involvement occur.
Infantile fibrosarcoma (IF) is a well characterized pediatric malignancy marked by gene rearrangements involving members of the NTRK family. In this report, we present a case of IF that presented in the inguinal region-proximal thigh and was initially thought to be a kaposiform hemangioendothelioma (KHE) because it presented with a bleeding diathesis thought to be Kasabach-Merritt phenomenon (KMP). Subsequently, the placental examination showed a neoplasm in the perivascular-subendothelial space of stem villi, initially thought to be myofibromatosis. Ultimately, a biopsy of the thigh mass showed IF with an NTRK3-ETV6 fusion. Subsequent FISH analysis of the placenta showed an ETV6 rearrangement confirming that it was also IF. Review of the laboratory studies suggests that disseminated intravascular coagulation may have been more likely than KMP, highlighting the difficulty in making this distinction in some cases. We believe this to be the first report of an IF presenting in a soft tissue site and the placenta, and discuss the possible mechanisms that could have allowed the IF in the leg to spread to the placenta.
The ATP-binding cassette transporter member A3 (ABCA3) is a lipid transporter with a critical function in pulmonary surfactant biogenesis. Biallelic loss-of-function mutations in ABCA3 result in severe surfactant deficiency leading to neonatal respiratory failure with death in the first year of life. Herein, we describe a newborn with severe respiratory distress at birth progressing to respiratory failure requiring transplant. This patient was found to have a maternally inherited frameshift loss-of-function ABCA3 mutation and a paternally inherited synonymous variant in ABCA3 predicted to create a cryptic splice site. Additional studies showed reduced ABCA3 expression in hyperplastic alveolar epithelial type II cells and lamellar body alterations characteristic of ABCA3 deficiency, leading to a diagnosis of autosomal recessive ABCA3-related pulmonary surfactant dysfunction. This case highlights the need for an integrated, comprehensive approach for the diagnosis of inherited diseases when in silico modeling is utilized in the interpretation of key novel genetic mutations.
Previous animal models of intestinal ischemia-reperfusion have been successful in causing considerable mucosal damage, cellular destruction and sepsis. However, this often results in the death of the animal, making it impossible to examine the effects of modulators of the ischemic event. The sequence of morphologic and physiologic changes in the bowel from such injuries continues to be an area of intense examination. We have studied these changes by producing segmental intestinal ischemia in vivo in a rat model. By occluding a first-order branch of the superior mesenteric artery (SMA) and by selectively ligating terminal collateral branches, reproducible segmental intestinal ischemia was achieved. Bowel damage ranged from alterations in the villus structure to frank hemorrhagic necrosis of the intestinal wall. This model allows the study of hypoperfusion injury to the small intestine without total SMA occlusion, thus reducing the overall mortality.
1. Ariel Stein, MD*,†
2. Helena Molero, MD*,†
3. Donavon Hess, MD, PhD*,‡
4. Mark Luquette, MD*,§
5. Michael B. Pitt, MD*,†
1. *University of Minnesota School of Medicine, Minneapolis, MN
2. †Department of Pediatrics
3. ‡Department of Surgery, and
4. §Department of Laboratory Medicine, University of Minnesota Masonic Children’s Hospital, Minneapolis, MN
* Abbreviations:
CPAM: : congenital pulmonary airway malformation
ED: : emergency department
RSV: : respiratory syncytial virus
A 5-month-old previously healthy term male infant presents to a rural emergency department (ED) for a 1-week history of increasing congestion, poor oral intake, and a temperature of 103°F (39.4°C). He is being treated with amoxicillin for presumed pneumonia. His examination in the ED is significant for scattered rhonchi and mild dehydration. His chest radiograph reveals inflammatory changes without a focal infiltrate (Fig 1). However, because this is his fourth presentation to the ED during this illness, he is admitted for observation. During the next 2 days his respiratory distress and tachypnea progressively worsen. On day 3 of his hospitalization he begins having episodes of desaturation and worsening retractions refractory to oxygen via low-flow nasal cannula. His examination at this time is significant for diffuse rhonchi throughout both lung fields with decreased air entry at the lung bases. Because his clinical status is deteriorating, he is transferred to a higher level of care.
Figure 1.
Anteroposterior and lateral chest radiographs on hospital day 1 show patchy, predominantly perihilar airspace opacities, consistent with viral inflammatory/reactive airway disease. No lobar consolidation. No pneumothorax.
On arrival at the referral center he is lethargic, with decreased breath sounds and persistent desaturations. A respiratory swab polymerase chain reaction is positive for respiratory syncytial virus (RSV). His chest radiograph reveals a large right-sided tension pneumothorax (Fig 2). A pigtail chest tube is emergently placed, and his work of breathing improves. Within 2 days he is no longer requiring supplemental oxygen. The medical team is unable to successfully put the chest tube to water seal, however, because each time it is sealed there is a rapid re-accumulation of his pneumothorax. After several unsuccessful attempts, his chest tube is placed back to suction and he is airlifted, via helicopter, to a pediatric tertiary care center for further evaluation, now 11 …
