Progressive Interstitial Lung Disease Following Hematopoietic Stem Cell Transplantation for Combined Immunodeficiency: A Novel Homozygous SLC7A7 Variant Suggestive of Lysinuric Protein Intolerance
Year: 2026
Type: article
Study design: Case Report
Abstract: Lysinuric protein intolerance (LPI) is a rare autosomal recessive metabolic disorder caused by biallelic pathogenic variants in SLC7A7, encoding the y+LAT1 transporter responsible for dibasic amino acid absorption in the intestine and reabsorption in the kidney. LPI can cause severe pulmonary disease, including alveolar proteinosis and fibrosing interstitial lung disease (ILD), which may be indistinguishable from post-transplant pulmonary complications. We report a case of an eight-year-old boy with a history of T-B-NK+ combined immunodeficiency (CID) successfully treated with allogeneic hematopoietic stem cell transplantation (HSCT), who subsequently developed progressive ILD. Whole exome sequencing (WES) identified a novel homozygous missense variant in SLC7A7 (c.265T>C; p.Cys89Arg), classified as a variant of uncertain significance (VUS) with high in silico pathogenicity scores (REVEL 0.94) and not previously reported in population databases. The variant was absent from gnomAD v4.1.0. This case underscores the diagnostic challenge of distinguishing LPI-associated pulmonary disease from post-transplant ILD, illustrates the utility of WES in the evaluation of unexplained post-transplant complications, and highlights the importance of plasma and urine amino acid chromatography in the biochemical confirmation of this diagnosis. To our knowledge, this is the first reported case of a homozygous SLC7A7 VUS co-occurring with a prior diagnosis of CID and HSCT, raising the possibility that the pulmonary phenotype may be attributable to LPI rather than to transplant-related causes alone.
Source: Cureus
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7220467392