Optical coherence tomography features in brothers with aspartylglucosaminuria

Goodspeed, Kimberly; Harder, Lana; Hughes, Samuel; Conger, Darrel; Taravella, Julia; Gray, Steven J.; Minassian, Berge A.

doi:10.1002/acn3.672

Cited by 3 publications

(8 citation statements)

References 13 publications

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“… 18 Thalamic T2 hypointensities are seen in other LSDs, but in AGU, it is most conspicuous within the pulvinar nucleus. 17 , 18 , 19 , 20 , 21 Additional studies have identified corresponding signal hypointensity on susceptibility‐weighted imaging in the pulvinar nuclei, suggesting this may be due to iron deposition, as has been described in other LSDs. 22 , 23 This finding may correlate with the neuropsychological functioning of these individuals as the pulvinar nuclei play an important role in attention and executive functioning.…”

Section: Introductionmentioning

confidence: 74%

“…Participants 1, 2, 7, and 8 have been included in prior publications. 10 , 21 , 32 , 33 a Non‐sense variant. b Fin Minor variant.…”

Section: Resultsmentioning

confidence: 99%

“…Auto‐fluorescent inclusion bodies were observed in two participants (one previously reported and finding was stable). 21 The second patient identified with auto‐fluorescent inclusion bodies was the oldest Finnish patient. The p100 was absent on flash VEP for both participants.…”

Section: Resultsmentioning

confidence: 99%

“…Optical coherence tomography (OCT) and blue light autofluorescence imaging were performed using the Spectralis OCT, as previously described. 21 , 28 All scans were obtained by a single operator under low‐light conditions without mydriasis. Peripapillary scans and macular scans of a 3 × 3 mm area by high‐speed protocol were acquired as tolerated.…”

Section: Methodsmentioning

confidence: 99%

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A cross‐sectional natural history study of aspartylglucosaminuria

et al. 2022

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Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder that causes stagnation of development in adolescence and neurodegeneration in early adulthood. Precision therapies, including gene transfer therapy, are in development with a goal of taking advantage of the slow clinical course. Understanding of disease natural history and identification of disease‐relevant biomarkers are important steps in clinical trial readiness. We describe the clinical features of a diverse population of patients with AGU, including potential imaging and electrophysiological biomarkers. This is a single‐center, cross‐sectional study of the clinical, neuropsychological, electrophysiological, and imaging characteristics of AGU. A comprehensive assessment of eight participants (5 Non‐Finnish) revealed a mean non‐verbal IQ (NVIQ) of 70.25 ± 10.33 which decreased with age (rs = −0.85, p = 0.008). All participants demonstrated deficits in communication and gross/fine motor dysfunction. Auditory and visual evoked potentials demonstrated abnormalities in one or both modalities in 7 of 8 subjects, suggesting sensory pathway dysfunction. Brain imaging demonstrated T2 FLAIR hypointensity in the pulvinar nuclei and cerebral atrophy, as previously shown in the Finnish AGU population. Magnetic resonance spectroscopy (MRS) showed a 5.1 ppm peak corresponding to the toxic substrate (GlcNAc‐Asn), which accumulates in AGU. Our results showed there was no significant difference between Finnish and Non‐Finnish patients, and performance on standardized cognitive and motor testing was similar to prior studies. Age‐related changes on functional assessments and disease‐relevant abnormalities on surrogate biomarkers, such as MRS, could be used as outcome measures in a clinical trial.

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Section: Introductionmentioning

confidence: 74%

“…Participants 1, 2, 7, and 8 have been included in prior publications. 10 , 21 , 32 , 33 a Non‐sense variant. b Fin Minor variant.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A cross‐sectional natural history study of aspartylglucosaminuria

et al. 2022

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“…Auto-fluorescent inclusion bodies and thickened retinal nerve fiber layer were described in a pair of brothers with AGU although clinical significance of this finding is unclear. 39…”

Section: Disease Overviewmentioning

confidence: 99%

Aspartylglucosaminuria: Clinical Presentation and Potential Therapies

Goodspeed

Feng²,

Lainé

et al. 2021

J Child Neurol

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Aspartylglucosaminuria (AGU) is a recessively inherited neurodegenerative lysosomal storage disease characterized by progressive intellectual disability, skeletal abnormalities, connective tissue overgrowth, gait disturbance, and seizures followed by premature death. AGU is caused by pathogenic variants in the aspartylglucosaminidase ( AGA) gene, leading to glycoasparagine accumulation and cellular dysfunction. Although more prevalent in the Finnish population, more than 30 AGA variants have been identified worldwide. Owing to its rarity, AGU may be largely underdiagnosed. Recognition of the following early clinical features may aid in AGU diagnosis: developmental delays, hyperactivity, early growth spurt, inguinal and abdominal hernias, clumsiness, characteristic facial features, recurring upper respiratory and ear infections, tonsillectomy, multiple sets of tympanostomy tube placement, and sleep problems. Although no curative therapies currently exist, early diagnosis may provide benefit through the provision of anticipatory guidance, management of expectations, early interventions, and prophylaxis; it will also be crucial for increased clinical benefits of future AGU disease-modifying therapies.

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