Measurement of lysosomal enzyme activities: A technical standard of the American College of Medical Genetics and Genomics (ACMG)

Strovel, Erin T.; Cusmano‐Ozog, Kristina; Wood, Tim; Yu, Chunli

doi:10.1016/j.gim.2021.12.013

Cited by 12 publications

(7 citation statements)

References 59 publications

(57 reference statements)

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“…For Pompe, the prevalence was 1 diagnosis in 16 702 live births, similar to that reported in the US (1 diagnosis in 17 731 live births) . The incidence of Gaucher disease in this study (1 diagnosis in 25 054 newborns) was higher than the worldwide incidence (1 diagnosis per 100 000 live births) but lower than that in the Ashkenazi Jewish population (1 diagnosis per 450 births) . However, we did not identify any patient with MPS-I disease, which has a high incidence in Washington State and Taiwan …”

Section: Discussionsupporting

confidence: 79%

“…31 The incidence of Gaucher disease in this study (1 diagnosis in 25 054 newborns) was higher than the worldwide incidence (1 diagnosis per 100 000 live births) but lower than that in the Ashkenazi Jewish population (1 diagnosis per 450 births). 5 However, we did not identify any patient with MPS-I disease, which has a high incidence in Washington State and Taiwan. 32 As of June 2011, 62% of patients with Krabbe disease who were enrolled in the World-Wide Krabbe Registry manifested early-onset infantile form.…”

Section: Discussionmentioning

confidence: 79%

“…LSDs comprise nearly 60 distinct disease entities, most of which have autosomal recessive inheritance but a few of which have X-linked inheritance, including Fabry disease and mucopolysaccharidosis type II . The combined incidence of LSDs is estimated to be 1 in 4000 to 1 in 9000 live births according to a 2022 report by the American College of Medical Genetics and Genomics (ACMG) . LSDs can affect multiple organs, especially the central nervous system, and patients who are untreated may be at risk of lifelong disability or even death .…”

Section: Introductionmentioning

confidence: 99%

“… 3 , 4 The combined incidence of LSDs is estimated to be 1 in 4000 to 1 in 9000 live births according to a 2022 report by the American College of Medical Genetics and Genomics (ACMG). 5 LSDs can affect multiple organs, especially the central nervous system, and patients who are untreated may be at risk of lifelong disability or even death. 6 Treatment options for LSDs include enzyme replacement therapy, hematopoietic stem cell transplantation, and substrate reduction therapy.…”

Section: Introductionmentioning

confidence: 99%

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Newborn Screening for 6 Lysosomal Storage Disorders in China

Chang,

Zhan,

Liu

et al. 2024

JAMA Netw Open

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ImportanceNewborn screening (NBS) for lysosomal storage disorders (LSDs) is becoming an increasing concern in public health. However, the birth prevalence of these disorders is rarely reported in the Chinese population, and subclinical forms of diseases among patients identified by NBS have not been evaluated.ObjectiveTo evaluate the birth prevalence of the 6 LSDs in the Shanghai population and determine subclinical forms based on clinical, biochemical, and genetic characteristics.Design, Setting, and ParticipantsThis cohort study included 50 108 newborns recruited from 41 hospitals in Shanghai between January and December 2021 who were screened for 6 LSDs using tandem mass spectrometry (MS/MS). Participants with screen-positive results underwent molecular and biochemical tests and clinical assessments. Data were analyzed from January 2021 through October 2022.ExposuresAll participants were screened for Gaucher, acid sphingomyelinase deficiency (ASMD), Krabbe, mucopolysaccharidosis type I, Fabry, and Pompe diseases using dried blood spots.Main Outcomes and MeasuresPrimary outcomes were the birth prevalence and subclinical forms of the 6 LSDs in the Shanghai population. Disease biomarker measurements, genetic testing, and clinical analysis were used to assess clinical forms of LSDs screened.ResultsAmong 50 108 newborns (26 036 male [52.0%]; mean [SD] gestational age, 38.8 [1.6] weeks), the mean (SD) birth weight was 3257 (487) g. The MS/MS-based NBS identified 353 newborns who were positive. Of these, 27 newborns (7.7%) were diagnosed with 1 of 6 LSDs screened, including 2 newborns with Gaucher, 5 newborns with ASMD, 9 newborns with Krabbe, 8 newborns with Fabry, and 3 newborns with Pompe disease. The combined birth prevalence of LSDs in Shanghai was 1 diagnosis in 1856 live births, with Krabbe disease the most common (1 diagnosis/5568 live births), followed by Fabry disease (1 diagnosis/6264 live births), and ASMD (1 diagnosis/10 022 live births). Biochemical, molecular, and clinical analysis showed that early-onset clinical forms accounted for 3 newborns with positive results (11.1%), while later-onset forms represented nearly 90% of diagnoses (24 newborns [88.9%]).Conclusions and RelevanceIn this study, the combined birth prevalence of the 6 LSDs in Shanghai was remarkably high. MS/MS-based newborn screening, combined with biochemical and molecular genetic analysis, successfully identified and characterized newborns who were screen-positive, which may assist with parental counseling and management decisions.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Newborn Screening for 6 Lysosomal Storage Disorders in China

Chang,

Zhan,

Liu

et al. 2024

JAMA Netw Open

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“…Enzyme activities are routinely measured in plasma and leukocytes isolated from peripheral blood. The use of dried blood spots as an initial sample source has increasingly been developed for some enzymes [ 86 ].…”

Section: Diagnostic Work-up For Lsdsmentioning

confidence: 99%

Hepatomegaly and Splenomegaly: An Approach to the Diagnosis of Lysosomal Storage Diseases

Jerves Serrano,

Gold,

Cooper

et al. 2024

JCM

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Clinical findings of hepatomegaly and splenomegaly, the abnormal enlargement of the liver and spleen, respectively, should prompt a broad differential diagnosis that includes metabolic, congestive, neoplastic, infectious, toxic, and inflammatory conditions. Among the metabolic diseases, lysosomal storage diseases (LSDs) are a group of rare and ultrarare conditions with a collective incidence of 1 in 5000 live births. LSDs are caused by genetic variants affecting the lysosomal enzymes, transporters, or integral membrane proteins. As a result, abnormal metabolites accumulate in the organelle, leading to dysfunction. Therapeutic advances, including early diagnosis and disease-targeted management, have improved the life expectancy and quality of life of people affected by certain LSDs. To access these new interventions, LSDs must be considered in patients presenting with hepatomegaly and splenomegaly throughout the lifespan. This review article navigates the diagnostic approach for individuals with hepatosplenomegaly particularly focusing on LSDs. We provide hints in the history, physical exam, laboratories, and imaging that may identify LSDs. Additionally, we discuss molecular testing, arguably the preferred confirmatory test (over biopsy), accompanied by enzymatic testing when feasible.

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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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Measurement of lysosomal enzyme activities: A technical standard of the American College of Medical Genetics and Genomics (ACMG)

Cited by 12 publications

References 59 publications

Newborn Screening for 6 Lysosomal Storage Disorders in China

Newborn Screening for 6 Lysosomal Storage Disorders in China

Hepatomegaly and Splenomegaly: An Approach to the Diagnosis of Lysosomal Storage Diseases

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

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