Diagnosis of Chediak Higashi disease in a 67-year old woman.
lysosomal disorders
next generation sequencing
rare disorders
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
16
05
2020
revised:
22
07
2020
accepted:
21
08
2020
pubmed:
30
9
2020
medline:
25
6
2021
entrez:
29
9
2020
Statut:
ppublish
Résumé
Chediak-Higashi disease is a rare disease caused by bi-allelic mutations in the lysosomal trafficking regulator gene, LYST. Individuals typically present in early childhood with partial oculocutaneous albinism, a bleeding diathesis, recurrent infections secondary to immune dysfunction, and risk of developing hemophagocytic lymphohistiocytosis (HLH). Without intervention, mortality is high in the first decade of life. However, some individuals with milder phenotypes have attenuated hematologic and immunologic presentations, and lower risk of HLH. Both classic and milder phenotypes develop progressive neurodegeneration in early adulthood. Here we present a remarkable patient diagnosed with Chediak-Higashi disease at age 67, many decades after the diagnosis is usually established. Diagnosis was suspected by observing the pathognomonic granules within leukocytes, and confirmed by identification of bi-allelic mutations in LYST, reduced LYST mRNA expression, enlarged lysosomes within fibroblasts, and decreased NK cell lytic activity. This case further expands the phenotype of Chediak-Higashi disease and highlights the need for increased awareness. Individuals with milder phenotypes may escape early diagnosis, but identification is important for close monitoring of potential complications, and to further our understanding of the function of LYST.
Identifiants
pubmed: 32990340
doi: 10.1002/ajmg.a.61886
doi:
Substances chimiques
LYST protein, human
0
Vesicular Transport Proteins
0
Types de publication
Case Reports
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3007-3013Subventions
Organisme : NHGRI NIH HHS
ID : Intramural research program
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
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