Indian Pediatrics Case Reports (Jan 2023)
Mutation in methionyl-tRNA synthetase 1 causing pulmonary alveolar proteinosis
Abstract
Background: A chronic history of exertional dyspnea, dry cough, and fatigue, associated with reticulonodular ground-glass opacity indicates an underlying interstitial lung disease (ILD). Pulmonary alveolar proteinosis (PAP) is a rare cause of ILD, in which there is abnormal accumulation of surfactant material in alveoli, thereby impairing gaseous exchange. In children, PAP is usually due to genetic mutations. We report a child with PAP due to mutation in methionyl-transfer RNA synthetase 1 (MARS) gene. Clinical Description: An 8-year-old boy presented with persistent dry cough, and exercise-induced breathlessness for 2 years of age, associated with failure to gain weight. He had multiple exacerbations in the past, requiring common symptomatic treatment, but with minimal improvement. On presentation to us, the child had tachypnea, hypoxia (oxygen saturation [SpO2]: 85%), and Grade 2 clubbing, with bilateral fine crepitation in bilateral lung fields. Management and Outcome: The child was stabilized by providing oxygen via high-flow nasal cannula. Blood investigations were largely normal. His chest X-ray and computerized tomography (CT) of the chest were suggestive of childhood ILD. A lung biopsy revealed periodic acid–Schiff-positive eosinophilic granular material in the alveolar spaces without any fibrosis, suggesting a diagnosis of PAP. Next-generation sequencing revealed a compound heterozygous mutation of the MARS1 gene resulting in PAP. Parental segregation analysis showed each one to be a carrier of one of the genes. Therapeutic whole-lung lavage (WLL) was carried out, following which symptoms improved markedly. SpO2 increased and the child was able to be weaned off oxygen and discharged. Three years, postdischarge, the child is asymptomatic and thriving well. Conclusions: PAP may be a cause of ILD in a child. Although the etiology can be ascertained by high-resolution CT of the chest and bronchoalveolar lavage, further genetic analysis should also be undertaken in children to identify the exact defect. WLL can provide a good outcome in children with PAP due to MARS mutation.
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