Childhood-onset myopathy with preserved ambulation caused by a recurrent ADSSL1 missense variant
Abstract: Background and Objectives
Distal myopathies are a heterogeneous group of primary muscle disorders with recessive or dominant inheritance. ADSSL1 is a muscle-specific adenylosuccinate synthase isoform involved in adenine nucleotide synthesis. Recessive pathogenic variants in the ADSSL1 gene located in chromosome 14q32.33 cause a distal myopathy phenotype. In this study, we present the clinical and genetic attributes of 6 Indian patients with this myopathy.
Methods This was a retrospective study describing on Indian patients with genetically confirmed ADSSL1 myopathy. Details were obtained from the medical records.
Results
All patients presented in their first or early second decade. All had onset in the first decade with a mean age at presentation being 17.7 ± 8.4 years (range: 3–27 years) and M:F ratio being 1:2. The mean disease duration was 9.3 ± 5.2 years ranging from 2 to 15 years. All patients were ambulant with wheelchair bound state in 1 patient due to respiratory involvement. The median serum creatine kinase (CK) level was 185.5 IU/L (range: 123–1564 IU/L). In addition to salient features of ptosis, cardiac involvement, bulbar weakness, and proximo-distal limb weakness with fatigue, there were significant seasonal fluctuations and decremental response to repetitive nerve stimulation, which have not been previously reported. Muscle histopathology was heterogenous with the presence of rimmed vacuoles, nemaline rods, intracellular lipid droplets along with chronic myopathic changes. Subtle response to pyridostigmine treatment was reported. While 5 of 6 patients had homozygous c.781G>A (p.Asp261Asn) variation, 1 had homozygous c.794G>A (p.Gly265Glu) in ADSSL1 gene.
Discussion
This study expands the phenotypic spectrum and variability of ADSSL1 myopathy with unusual manifestations in this rare disorder. Because the variant c.781G>A (p.Asp261Asn) is the most common mutation among Indian patients similar to other Asian cohorts, this finding could be useful for genetic screening of suspected patients
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Neurolog. Genetics. - 10, 1 (2024) , ISSN: 2376-7839
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2024
- Urheber
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Baskar, Dipti
Polavarapu, Kiran
Preethish-Kumar, Veeramani
Vengalil, Seena
Nashi, Saraswati
Töpf, Ana
Thomas, Aneesha
Sanka, Sai Bhargava
Menon, Deepak
Srivastava, Kosha
Arunachal, Gautham
Nandeesh, Bevinahalli
Lochmüller, Hanns
Nalini, Atchayaram
- DOI
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10.1212/nxg.0000000000200122
- URN
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urn:nbn:de:bsz:25-freidok-2532782
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:55 MEZ
Datenpartner
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Beteiligte
- Baskar, Dipti
- Polavarapu, Kiran
- Preethish-Kumar, Veeramani
- Vengalil, Seena
- Nashi, Saraswati
- Töpf, Ana
- Thomas, Aneesha
- Sanka, Sai Bhargava
- Menon, Deepak
- Srivastava, Kosha
- Arunachal, Gautham
- Nandeesh, Bevinahalli
- Lochmüller, Hanns
- Nalini, Atchayaram
- Universität
Entstanden
- 2024