Late‐onset pompe disease in Iran: A clinical and genetic report

Nazari, Ferdos; Sinaei, Farnaz; Nilipour, Yalda; Fatehi, Farzad; Streubel, Berthold; Ashrafi, Mahmoud Reza; Aryani, Omid; Nafissi, Shahriar

doi:10.1002/mus.25413

Cited by 8 publications

(6 citation statements)

References 14 publications

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“…However, the results reported for diagnostic delay vary considerably between countries. For instance, the diagnostic delay in cohorts from Austria, China, and Iran were 7.4, 5, and 3.3 years, respectively (17)(18)(19). Therefore, in the present study, the diagnostic delay was shorter than those previously observed.…”

Section: Discussioncontrasting

confidence: 49%

Clinical manifestations and acid alpha-glucosidase mutation characterisation of a cohort of patients with late-onset Pompe disease in eastern China

Zhao¹,

Zhi²,

Ying³

et al. 2021

Ann Transl Med

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Background: Pompe disease is a rare, progressive, and life-threatening autosomal recessive disorder. In its late-onset form, the disease is primarily characterised by mild progressive proximal limb and respiratory muscle weakness. Mutations in the acid alpha-glucosidase (GAA) gene cause lysosomal enzyme GAA to be significantly reduced or missing altogether, for which supplementation can be given through enzyme replacement therapy. Methods: Fourteen patients diagnosed with late-onset Pompe disease (LOPD) in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2021 were enrolled. GAA activity was measured based on enzymatic activity in dried blood spots, and next-generation sequencing was used to detect mutations in the GAA gene. The impacts of novel missense variants were determined by five different prediction algorithms. The structural figures of novel variants and their wide types were processed with PyMOL. Results: The study included 14 patients with LOPD (male-to-female ratio, 1:1) from eastern China. The median age at symptom onset and diagnosis was 15.0 years (7-36 years) and 21.5 years (8-47 years), respectively. The median diagnostic delay from onset was 3.0 years (0-22 years). Proximal muscle weakness was the first prominent symptom in 8 patients, while the other 6 patients experienced respiratory failure, chest congestion and asthma, and scoliosis. The most frequent mutation of the GAA gene was c.2238G>C (p.W746C), which was observed at an allele frequency of 14.3% (4/28) and in 28.6% of patients (4/14). Four novel variants potentially related to the pathogenicity of LOPD were found: c.1299G>C (p.Q433H), c.1409A>G (p.N470S), c.2242delG (p.E748Rfs*16), and c.2832delA (p.E945Sfs*78). Conclusions: The c.2238G>C (p.W746C) mutation was the most common mutation in 14 patients with LOPD from eastern China. This study has identified four novel variants in patients with LOPD. Predicting the pathogenicity of these novel variants may increase the understanding of the genetic mutation spectrum in LOPD. Our findings may also improve recognition of the characteristics of Chinese patients with LOPD.

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Section: Discussioncontrasting

confidence: 49%

Clinical manifestations and acid alpha-glucosidase mutation characterisation of a cohort of patients with late-onset Pompe disease in eastern China

Zhao¹,

Zhi²,

Ying³

et al. 2021

Ann Transl Med

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“…A cohort study in Austria revealed an even lower prevalence of 1:351,000 of Pompe disease (including both LOPD and infantile forms) [18]. Thus, LOPD is a rare disease, and the low prevalence may be one explanation for the long diagnostic delay of almost 13 years in our study, 7.4 years in the Austrian cohort [18], about 5 years in a Chinese patient group [19] and 3.3 years in an Iranian cohort [20]. Furthermore, the clinical presentation is variable and can be mild and non-specific, especially at the beginning of the disease.…”

Section: Lopd Is a Rare Disease And Associated With A Long Diagnosticmentioning

confidence: 41%

Late-onset Pompe disease (LOPD) in Belgium: clinical characteristics and outcome measures

Vanherpe

Fieuws

D’Hondt

et al. 2020

Orphanet J Rare Dis

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Background: Late-onset Pompe disease (LOPD) is a rare, hereditary, progressive disorder that is usually characterized by limb-girdle muscle weakness and/or respiratory insufficiency. LOPD is caused by mutations in the acid alpha-glucosidase (GAA) gene and treated with enzyme replacement therapy (ERT). Methods: We studied the clinical, brain imaging, and genetic features of the Belgian cohort of late-onset Pompe disease patients (N = 52), and explored the sensitivity of different outcome measures, during a longitudinal period of 7 years (2010-2017), including the activity limitations ActivLim score, 6 min walking distance (6MWD), 10 m walk test (10MWT), MRC sum score, and forced vital capacity (FVC) sitting/supine. Results: In Belgium, we calculated an LOPD prevalence of 3.9 per million. Mean age at onset of 52 LOPD patients was 28.9 years (SD: 15.8 y), ranging from 7 months to 68 years. Seventy-five percent (N = 39) of the patients initially presented with limb-girdle weakness, whereas in 13% (N = 7) respiratory symptoms were the only initial symptom. Non-invasive ventilation (NIV) was started in 37% (N = 19), at a mean age of 49.5 years (SD: 11.9 y), with a mean duration of 15 years (SD: 10.2 y) after symptom onset. Brain imaging revealed abnormalities in 25% (N = 8) of the patients, with the presence of small cerebral aneurysm(s) in two patients and a vertebrobasilar dolichoectasia in another two. Mean diagnostic delay was 12.9 years. All patients were compound heterozygotes with the most prevalent mutation being c.-32-13 T > G in 96%. We identified two novel mutations in GAA: c.1610_1611delA and c.186dup11. For the 6MWD, MRC sum score, FVC sitting and FVC supine, we measured a significant decrease over time (p = 0.0002, p = 0.0001, p = 0.0077, p = 0.0151), which was not revealed with the ActivLim score and 10MWT (p > 0.05). Conclusions: Awareness on LOPD should even be further increased because of the long diagnostic delay. The 6MWD, but not the ActivLim score, is a sensitive outcome measure to follow up LOPD patients.

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“…Case 2: This is an infant with two heterozygous pathogenic variants. The c.1979G>A variant has been associated with both IOPD and LOPD [ 35 , 36 ]; and the c.1754+1_1754+12delinsCCA variant has no reported link to Pompe disease but was deemed as disease-causing in general [ 37 ]. Confirmatory tests found reduced GAA enzyme activity and mildly elevated Hex4.…”

Section: Resultsmentioning

confidence: 99%

The First Year Experience of Newborn Screening for Pompe Disease in California

Tang

Feuchtbaum

Sciortino

et al. 2020

IJNS

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The California Department of Public Health started universal newborn screening for Pompe disease in August 2018 with a two-tier process including: (1) acid alpha-glucosidase (GAA) enzyme activity assay followed by, (2) GAA gene sequencing analysis. This study examines results from the first year of screening in a large and diverse screening population. With 453,152 screened newborns, the birth prevalence and GAA enzyme activity associated with various types of Pompe disease classifications are described. The frequency of GAA gene mutations and allele variants are reported. Of 88 screen positives, 18 newborns were resolved as Pompe disease, including 2 classic infantile-onset and 16 suspected late-onset form. The c.-32-13T>G variant was the most common pathogenic mutation reported. African American and Asian/Pacific Islander newborns had higher allele frequencies for both pathogenic and pseudodeficiency variants. After the first year of Pompe disease screening in California, the disease distribution in the population is now better understood. With the ongoing long-term follow-up system currently in place, our understanding of the complex genotype-phenotype relationships will become more evident in the future, and this should help us better understand the clinical significance of identified cases.

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Late‐onset pompe disease in Iran: A clinical and genetic report

Abstract: This is a comprehensive report of LOPD in Iranian patients. Distinct phenotypic and genotypic features in this population are highlighted. Muscle Nerve 55: 835-840, 2017.

Cited by 8 publications

References 14 publications

Clinical manifestations and acid alpha-glucosidase mutation characterisation of a cohort of patients with late-onset Pompe disease in eastern China

Clinical manifestations and acid alpha-glucosidase mutation characterisation of a cohort of patients with late-onset Pompe disease in eastern China

Late-onset Pompe disease (LOPD) in Belgium: clinical characteristics and outcome measures

The First Year Experience of Newborn Screening for Pompe Disease in California

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