Hartnup disease presenting as hereditary spastic paraplegia and severe peripheral neuropathy.
Hartnup disease
hereditary spastic paraplegia
peripheral neuropathy
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:
01 2022
01 2022
Historique:
revised:
11
07
2021
received:
17
05
2021
accepted:
10
08
2021
pubmed:
31
8
2021
medline:
8
4
2022
entrez:
30
8
2021
Statut:
ppublish
Résumé
Hartnup disease cases were rare, and the genotype-phenotype correlation was not fully understood. Here we reported two unrelated young men diagnosed as Hartnup disease, who carried novel compound heterozygote mutations in the SLC6A19 gene and presented with new phenotypes. Other than intermittent encephalopathy and photosensitive rashes, they displayed symptoms and signs of spastic paraplegia and severe peripheral nerve damages. Magnetic resonance imaging showed mild bilateral cerebellar atrophy and thinning of the thoracic spinal cord. Electromyogram detected mixed sensorimotor polyneuropathy in lower limbs. Sural nerve biopsy and pathological study indicated the moderately reduced neural fibers in the periphery nerves. Urinary amino acid analysis showed increased levels of multiple neutral amino acids. Moreover, muscle strengths in the lower limbs and the walking ability have been improved in both cases (MRC 3/5 to 4/5 in Patient 1; walking distance elongated from 50 to 100 m in Patient 2) after the treatment with oral nicotinic acid and intravenous injection of multiple amino acids. Exome sequencing revealed and confirmed the existence of the novel compound heterozygous SLC6A19 mutations: c.533G>A (p.Arg178Gln) and c.1379-1G>C mutations in patient1, and c.1433delG (p.Gly478AlafsTer44) and c.811G>A (p.Ala271Thr) in patient 2. Taken together, these findings expanded the clinical, neuroimaging, pathology, and genetic spectrum of Hartnup disease. However, the co-existence of HSP and peripheral neuropathy was only inferred based on clinical observations, and pathological and molecular studies are needed to further dissect the underlying mechanisms.
Identifiants
pubmed: 34459558
doi: 10.1002/ajmg.a.62475
doi:
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
237-242Informations de copyright
© 2021 Wiley Periodicals LLC.
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