An Unusual Cause of Respiratory Distress in Term Neonate.

We report a female infant who was born at 41+6 weeks of gestation to a consanguineous parent, and the initial newborn examination was within normal. At 12 hours of age, she developed tachypnea; with desaturation, she had continuous thick whitish oral secretion. Admitted to the neonatal intensive care unit (NICU) for further management, her initial blood investigation, including blood gas and chest X-ray, was normal. Due to the persistent unexplained respiratory distress with a normal chest X-ray, we obtained a further history from parents with three siblings with respiratory symptoms but no definitive diagnosis. The genetic testing of whole-exome sequences (WES) confirmed a homozygous variant c.804_806del, p.(Lys268del) in the RSPH9 gene that causes primary ciliary dyskinesia (PCD). Her three siblings were tested and found to have the same genetic mutation.

IPEX Syndrome with Normal FOXP3 Protein Expression in Treg Cells in an Infant Presenting with Intractable Diarrhea as a Single Symptom.

IPEX (immune dysregulation-polyendocrinopathy-enteropathy-X-linked) syndrome is a rare, potentially fatal multisystem disorder caused by mutations in the FOXP3 gene. This can lead to quantitative or functional deficiency of regulatory T cells (Treg), thereby affecting their immune-suppressive actions which can in turn cause autoimmune and inflammatory disorders. We describe an infant with IPEX syndrome with unremarkable maternal family history whose only presentations were severe diarrhea and malnutrition. The patient had a normal percentage of Treg cells and FOXP3 protein expression, but further testing revealed a hemizygous missense mutation in the FOXP3 gene. IPEX syndrome should be considered in young children even if severe intractable diarrhea is the only symptom with no other autoimmune manifestations. Sequencing of the FOXP3 gene should always be considered for accurate diagnosis to look for mutations even in the face of normal FOXP3 protein expression in the Treg cell.

Evaluation of the pulmonary radioaerosol mucociliary clearance scan as an adjunctive test for the diagnosis of primary ciliary dyskinesia in children.

INTRODUCTION: The accuracy of primary ciliary dyskinesia (PCD) diagnosis has improved but no single test is diagnostic and some cases remain unsolved. Data regarding the accuracy of pulmonary radioaerosol mucociliary clearance scan (PRMCC) for the diagnosis of PCD are limited to predominantly adults using a 24-hour test. This study was performed to determine the accuracy of a 60-minute PRMCC test for diagnosing PCD in children. METHODS: Children with suspected PCD and inconclusive clinical diagnostic testing in an expert center were selected for PRMCC testing. Nebulized 99m Tc sulfur colloid was inhaled and dynamic imaging acquired for 60 to 120 minutes. Two independent radiologists blinded to the clinical diagnosis and health records overread PRMCC studies. The PRMCC result was compared with the reference standard diagnosis of PCD made by two physicians using the cumulative health record, blinded to PRMCC results. RESULTS: From 2008 to 2018, 57 patients (6-17 years) participated, of which 16 met criteria for the reference diagnosis of PCD. The PRMCC test was conclusive in 54 patients (94.7%) and had a sensitivity of 100% (95% confidence interval [CI] = 78.2-100), specificity of 85.7% (95% CI = 69.7-95.2), positive predictive value of 75% (95% CI = 57.1-87.1), negative predictive value of 100% (95% CI = 90.2-100), and accuracy of 90% (95% CI = 78.2-96.7). CONCLUSION: The 60-minute PRMCC test is noninvasive and feasible in children with a high negative predictive value for PCD. It may be a helpful adjunctive test to rule out PCD when clinical suspicion remains after guideline recommended first-line clinical testing.

Severe disease due to CCDC40 gene variants and the perils of late diagnosis in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) can manifest in the neonatal period with severe respiratory distress. We describe a child with PCD who presented at term with severe neonatal respiratory distress, persistent right upper lobe collapse and failure to thrive who underwent lobectomy prior to the diagnosis of PCD at the age of 3 years. This case report illustrates the severe spectrum of lung disease associated with coiled-coil domain containing protein 40 (CCDC40) gene variants in patients with PCD.

Efficacy of high-dose steroids for bronchiolitis obliterans syndrome post pediatric hematopoietic stem cell transplantation.

BOS is the pulmonary manifestation of cGvHD post-allogeneic HSCT. Survival and treatment of this often fatal complication have not improved over the last 20 years and there is no clear standard of care. For the past 10 years, BOS was treated in our center with monthly cycles of HDPS. We reviewed the outcomes of patients with post-HSCT BOS who met the diagnostic criteria for BOS as per the NIH consensus and were treated with at least one cycle of methylprednisolone at a dose of 10-30 mg/kg/d×3 d. We collected demographic and clinical data, responses to treatment and results of pulmonary function tests at several time points. Between January 2007 and January 2014, 12 patients were treated with HDPS for post-HSCT BOS. Five patients (42%) had a good response to treatment; four patients (33%) stabilized with moderate lung disease; and three patients (25%) progressed to end-stage disease. No significant acute side effects attributable to the HDPS treatment were identified. HDPS may be an effective treatment option for all but the most severely ill patients with post-HSCT BOS.

Bronchiolitis obliterans organising pneumonia associated with anticonvulsant hypersensitivity syndrome induced by lamotrigine.

A 14-year-old girl who was known to have a seizure disorder and on lamotrigine treatment was admitted to the hospital, with a history of rash, fever and cough. Her condition deteriorated with clinical features suggestive of anticonvulsant hypersensitivity syndrome (ACHS) complicated with bronchiolitis obliterans organising pneumonia (BOOP). Her chest CT showed multifocal parenchymal opacities and lung biopsy was typical for BOOP. Initially, the lamotrigine was discontinued since the onset of the rash, then she was treated for pneumonia with antibiotics, which may have delayed the diagnosis. Eventually, BOOP was considered and she was treated with a high dose of corticosteroid. She improved clinically and her repeated chest CT showed a marked resolution of the lesions. This case illustrates the possible occurrence of BOOP as a complication of ACHS secondary to lamotrigine treatment.