High-risk screening of late-onset Pompe disease: A different early portrait in China

Jiao, Kexin; Jiang, Dong; Luo, Sushan; Yu, Liqiang; Ke, Qing; Wang, Zhiqiang; Luan, Xinghua; Zhang, Xiaojie; Guo, Jing; Chen, Yan; Li, Xihua; Tan, Shun; Qian, Fangyuan; Jiang, Jianming; Yu, Xuen; Yue, Dongyue; Liu, Changxia; Luo, Lijun; Li, Jianping; Qu, Yanzhou; Chen, Lan; Tu, Jiyuan; Sun, Chong; Chong, Yidong; Song, Jié; Xi, Jianying; J, Lin; Lu, Jiahong; Zhao, Chongbo; Zhu, Wenhua; Fang, Qi

doi:10.3389/fneur.2022.965207

Cited by 3 publications

(6 citation statements)

References 41 publications

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“…The c.2238G>C (p.W746C) variant was the most prevalent, found in 32.4% (22/68) of alleles. Besides the previously reported c.568C>G (p.R190G) and c.1928G>C (p. G643A), 17 two novel variants, c.1444C>T (p.P482S) and c.521A>G (p.E174G), were identified in two independent patients, respectively. They were categorized as “Likely pathogenic” and “uncertain significance” according to established criteria, respectively (Table S2 ).…”

Section: Resultsmentioning

confidence: 61%

“…This indicates that China is still an underrepresented region, in which the full genetic landscape of LOPD remains uncharted. Nevertheless, the finding that hyperCKemia was rarely solely presented as an initial symptom illustrated a different early portrait of Chinese LOPD 17–21 …”

Section: Discussionmentioning

confidence: 99%

“…Unlike in south China where most of the childhood‐onset LOPD are carriers of the c.1935C>A variant, 15 in our study carriers of c.2238G>C variant with the manifestation in adolescence presented with LGMW with/without hyperCKemia instead of early respiratory failure. On the other hand, compared to populations that carriers of the leaky splicing mutation IVS1 comprising the majority of adult LOPD patients, adult‐onset patients with c.2238G>C tended to develop respiratory insufficiency earlier 17,26 . Whether there are other phenotypic modifiers at play besides the hotspots remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the finding that hyperCKemia was rarely solely presented as an initial symptom illustrated a different early portrait of Chinese LOPD. [17][18][19][20][21] The prompt diagnosis in patients presenting LGMW symptoms is challenging due to its non-specificity in a variety of neuromuscular disorders and other systemic conditions. The red flag of Pompe disease would not be raised until histological studies revealed vacuolar myopathy with excessive glycogen, resulting in diagnostic delay in general approach of differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the finding that hyperCKemia was rarely solely presented as an initial symptom illustrated a different early portrait of Chinese LOPD. 17 , 18 , 19 , 20 , 21 …”

Section: Discussionmentioning

confidence: 99%

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Diagnostic delay in late‐onset Pompe disease among Chinese patients: A retrospective study

Yue,

Jiao,

Xia

et al. 2023

JIMD Reports

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Surveys and retrospective studies have revealed considerable delays in diagnosing late‐onset Pompe disease (LOPD) in China, where the contributing factors remain poorly represented. Our study analyzed the diagnostic journey of 34 LOPD patients seen at our neuromuscular clinic from 2005 to 2022. We defined diagnostic delay as the time from the onset of the first relevant symptoms and laboratory findings suggestive of LOPD to the eventual diagnosis, and we constructed a correlation matrix to assess relationships among these variables. The cohort consisted of 34 patients with an equal male‐to‐female ratio, and the mean age at diagnosis was 27.68 ± 10.03 years. We found the median diagnostic delay to be 5 years, with a range of 0.3 to 20 years, with 97.1% having been misdiagnosed previously, most commonly with “Type II Respiratory insufficiency” (36.7%). Notably, patients at earlier onset (mean age, 18.19 years vs. 31 years; p < 0.005) tended to have higher creatine kinase (CK) levels. Furthermore, 92.6% reported difficulty in sitting up from a supine position since childhood. Our research emphasizes the role of early indicators like dyspnea and difficulty performing sit‐ups in adolescents for timely LOPD diagnosis and treatment initiation. The importance of early high‐risk screening using dried blood spot testing cannot be overstated.

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Section: Resultsmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the finding that hyperCKemia was rarely solely presented as an initial symptom illustrated a different early portrait of Chinese LOPD. 17 , 18 , 19 , 20 , 21 …”

Section: Discussionmentioning

confidence: 99%

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Diagnostic delay in late‐onset Pompe disease among Chinese patients: A retrospective study

Yue,

Jiao,

Xia

et al. 2023

JIMD Reports

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High‐risk screening for late‐onset Pompe disease in China: An expanded multicenter study

Jiao,

Zhu,

Chang

et al. 2024

J of Inher Metab Disea

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Late‐onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha‐glucosidase (GAA), leading to progressive limb‐girdle weakness and respiratory impairment. The insidious onset of non‐specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high‐risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty‐four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb‐girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high‐risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high‐risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

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Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1

Zhong,

Zeng,

et al. 2024

Orphanet J Rare Dis

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Background As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. Methods Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. Results Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12–74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92–1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. Conclusion The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.

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High-risk screening of late-onset Pompe disease: A different early portrait in China

Cited by 3 publications

References 41 publications

Diagnostic delay in late‐onset Pompe disease among Chinese patients: A retrospective study

Diagnostic delay in late‐onset Pompe disease among Chinese patients: A retrospective study

High‐risk screening for late‐onset Pompe disease in China: An expanded multicenter study

Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1

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