Skip to content
DraconiticResearch
Search Sources API
203,203 studies31 sourcesUpdated 20 min ago
Peer-reviewedCC BY 4.0Cureus

Progressive Interstitial Lung Disease Following Hematopoietic Stem Cell Transplantation for Combined Immunodeficiency: A Novel Homozygous SLC7A7 Variant Suggestive of Lysinuric Protein Intolerance

  • Sara Babour1
  • Hassani Amale2
  • Radi Abdelilah3
  • Rachid Abilkassem2
  1. 1Pediatric Rheumatology, Mohammed V Military Training Hospital, Rabat, MAR
  2. 2Pediatric Medicine, Mohammed V Military Training Hospital, Rabat, MAR
  3. 3Pediatric Critical Care, Mohammed V Military Training Hospital, Rabat, MAR
Read full textPDFDOICite

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.

Related

  1. Automated quantitative analysis can support the identification of progressive pulmonary fibrosis in fibrotic interstitial lung disease.
    Emma Janska, Giles Dixon, Joseph Page +8
    BMJ open respiratory researchPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  2. The role of allogeneic hematopoietic stem cell transplantation in adults with mature T‐cell lymphomas
    Laura Diana Stocker, Lisa Thielecke, Constantin Schmitz +3
    The Cochrane Database of Systematic ReviewsPeer-reviewedPublisher termsFull textGeneral medicinePMC
  3. A randomized controlled trial of a multidisciplinary collaborative fatigue management program for patients undergoing hematopoietic stem cell transplantation: study protocol
    Jianli Zhang, Liya Ren, Liwei Xu +5
    TrialsPeer-reviewedCC BY-NC-ND 4.0OncologyCrossref
  4. Case Report: SAPHO syndrome mimicking osseous relapse after haploidentical allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia
    Wenhui Zhang, Xiaolin Ma, Xianglan Liu +6
    Frontiers in medicinePeer-reviewedCC BYFull textGeneral medicineEurope PMC
  5. Variability of Nutritional Status During Hematopoietic Stem Cell Transplantation and Its Association With Clinical Outcomes: An Ambispective Observational Study From India
    Manasi Gupta, Himanshu Aggarwal, Ruma Singh +6
    CureusPeer-reviewedCC BYFull textGeneral medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{babour2026progressive,
  title = {{Progressive Interstitial Lung Disease Following Hematopoietic Stem Cell Transplantation for Combined Immunodeficiency: A Novel Homozygous SLC7A7 Variant Suggestive of Lysinuric Protein Intolerance}},
  author = {Sara Babour and Hassani Amale and Radi Abdelilah and Rachid Abilkassem},
  journal = {Cureus},
  year = {2026},
  month = oct,
  doi = {10.7759/cureus.117465},
  url = {https://doi.org/10.7759/cureus.117465},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Progressive Interstitial Lung Disease Following Hematopoietic Stem Cell Transplantation for Combined Immunodeficiency: A Novel Homozygous SLC7A7 Variant Suggestive of Lysinuric Protein Intolerance
AU  - Sara Babour
AU  - Hassani Amale
AU  - Radi Abdelilah
AU  - Rachid Abilkassem
PY  - 2026
DA  - 2026/10/05
JO  - Cureus
DO  - 10.7759/cureus.117465
UR  - https://doi.org/10.7759/cureus.117465
AB  - 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.
SN  - 2168-8184
ER  -