# Case report: Infantile pulmonary alveolar proteinosis associated with cytosolic isoleucyl-tRNA synthetase deficiency

## TL;DR

A rare genetic disorder involving IARS1 deficiency was found in a 5-month-old boy with lung disease as the main symptom.

## Contribution

This is the first report of IARS1 deficiency presenting with PAP as the initial manifestation in an infant.

## Key findings

- The patient showed PAP as the primary symptom of IARS1 deficiency.
- Whole-exome sequencing revealed two novel compound heterozygous variants in the IARS1 gene.
- This case expands the clinical spectrum of IARS1 deficiency.

## Abstract

Cytosolic isoleucyl-tRNA synthetase (IARS1) deficiency, an exceptionally rare autosomal recessive inherited disorder, is characterized by multiple system involvement, including growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy. Pulmonary alveolar proteinosis (PAP) is a rare phenotype of IARS1 deficiency, having been reported in only two siblings from the same family. In this study, we present a case of IARS1 deficiency in a 5-month-old boy, who exhibited PAP as the initial and predominant manifestation. Additionally, whole-exome sequencing identified compound heterozygous variants in the IARS1 gene (c.2428C>T/c.128T>C), both of which are novel observations.