Very Early Treatment for Infantile-Onset Pompe Disease Contributes to Better Outcomes

Yang, Chia Feng; Yang, Chen Chang; Liao, Hsuan Chieh; Huang, Ling; Chiang, Chuan Chi; Ho, Hui Chen; Lai, Chih Jou; Chu, Tzu Hung; Yang, Tsui; Hsu, Ting-Rong; Soong, Wen‐Jue; Niu, Dau Ming

doi:10.1016/j.jpeds.2015.10.078

Cited by 89 publications

(92 citation statements)

References 28 publications

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“…It is broadly classified into classic infantile Pompe disease (IOPD), the most severe end of the spectrum with rapidly progressive hypertrophic cardiomyopathy at birth, generalized muscle weakness, and death within the first two years of life without treatment [2 3]; and late onset Pompe disease (LOPD), encompassing childhood, juvenile, and adult-onset disease, with variable severity of muscle involvement, presenting anywhere from infancy to the sixth decade of life [4–6]. Enzyme replacement therapy (ERT) with alglucosidase alfa remains the only FDA approved treatment for Pompe disease with evidence that early initiation of treatment results in best outcomes with dramatically improved survival [7–9]. …”

Section: Introductionmentioning

confidence: 99%

Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T > G “late-onset” GAA variant

Rairikar

Case

Bailey

et al. 2017

Molecular Genetics and Metabolism

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Objective Newborn screening (NBS) has led to early diagnosis and early initiation of treatment for infantile onset Pompe Disease (IOPD). However, guidelines for management of late onset Pompe disease (LOPD) via NBS, especially with the IVS c.-32-13T>G are not clear. This IVS variant is noted in 68–90% cases with LOPD and has been presumed to result in “adult” disease in compound heterozygosity, with a few cases with earlier onset and a mild to no phenotype in homozygosity. Our study evaluates newborns with LOPD having IVS variant with a diligent multidisciplinary approach to determine if they have an early presentation. Methods Seven children with LOPD identified by NBS with IVS variant (3 compound heterozygous, and 4 homozygous) were evaluated with clinical, biochemical (CK, AST, ALT, and urinary Glc4), cardiac evaluation, physical therapy (PT), occupational, and speech/language therapy. Results All seven patients demonstrated motor involvement by age 6 months; the three patients with c.-32-13 T>G variant in compound heterozygosity had symptoms as neonates. Patients with c.-32-13 T>G variant in compound heterozygosity had more involvement with persistent hyperCKemia, elevated AST and ALT, swallowing difficulties, limb-girdle weakness, delayed motor milestones, and were initiated on ERT. The patients with c.-32-13T>G variant in homozygosity had normal laboratory parameters, and presented with very subtle yet LOPD specific signs, identified only by meticulous assessments. Conclusion This patient cohort represents the first carefully phenotyped cohort of infants with LOPD with the “late-onset” GAA variant c.-32-13T>G detected by NBS in the USA. It emphasizes not only the opportunity for early detection of skeletal and other muscle involvement in infants with c.-32-13T>G variant but also a high probability of overlooking or underestimating the significance of clinically present and detectable features. It can thus serve as a valuable contribution in the development of evaluation and treatment algorithms for infants with LOPD.

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Section: Introductionmentioning

confidence: 99%

Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T > G “late-onset” GAA variant

Rairikar

Case

Bailey

et al. 2017

Molecular Genetics and Metabolism

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“…Their mean anti-rhGAA IgG antibody titer was 1230 (range 0–6400). Later, a second Taiwanese group conducted a NBS program for Pompe disease and found that even earlier administration of ERT in asymptomatic IOPD patients was associated with better outcomes [21]. In this study, 14 of 669,797 newborns screened were diagnosed with IOPD, including 13 who were diagnosed after 2010 when rapid screening became available.…”

Section: Discussionmentioning

confidence: 87%

Divergent clinical outcomes of alpha-glucosidase enzyme replacement therapy in two siblings with infantile-onset Pompe disease treated in the symptomatic or pre-symptomatic state

Matsuoka

Miwa

Tajika

et al. 2016

Molecular Genetics and Metabolism Reports

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Pompe disease is an autosomal recessive, lysosomal glycogen storage disease caused by acid α-glucosidase deficiency. Infantile-onset Pompe disease (IOPD) is the most severe form and is characterized by cardiomyopathy, respiratory distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally results in death within the first year of life. Enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly improve the life expectancy of patients with IOPD. However, the efficacy of ERT in patients with IOPD is affected by the presence of symptoms and cross-reactive immunologic material (CRIM) status.We have treated two siblings with IOPD with ERT at different ages: the first was symptomatic and the second was asymptomatic. The female proband (Patient 1) was diagnosed with IOPD and initiated ERT at 4 months of age. Her younger sister (Patient 2) was diagnosed with IOPD at 10 days of age and initiated ERT at Day 12. Patient 1, now 6 years old, is alive but bedridden, and requires 24-hour invasive ventilation due to gradually progressive muscle weakness. In Patient 2, typical symptoms of IOPD, including cardiac failure, respiratory distress, progressive muscle weakness, hepatomegaly and myopathic facial features were largely absent during the first 12 months of ERT. Her cardiac function and mobility were well-maintained for the first 3 years, and she had normal motor development. However, she developed progressive hearing impairment and muscle weakness after 3 years of ERT. Both siblings have had low anti-rhGAA immunoglobulin G (IgG) antibody titers during ERT and have tolerated the treatment well.These results suggest that initiation of ERT during the pre-symptomatic period can prevent and/or attenuate the progression of IOPD, including cardiomyopathy, respiratory distress, and muscle weakness for first several years of ERT. However, to improve the long-term efficacy of ERT for IOPD, new strategies for ERT for IOPD, e.g. modifying the enzyme to enhance uptake into skeletal muscle and/or to cross the blood brain barrier (BBB), will be required.

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“…If confirmed, a biochemical second-tier test for Pompe disease not only is more cost effective than molecular genetic analysis but also allows a faster turnaround time of results. To achieve best outcomes, 13 early-onset Pompe disease should be considered a time-critical condition for which newborn screening results should be made available to care providers by the 5th day of life, a goal not readily achievable when using molecular genetic analysis as a second-tier test. Another benefit of a reliable biochemical second-tier test is the avoidance of anxiety and costs associated with the frequent discovery of genotypes of uncertain significance, which eventually turn out to be unaffected individuals with pseudodeficient GAA activities.…”

Section: Discussionmentioning

confidence: 99%

“…8 Although response to enzyme replacement therapy is highly variable and complicated by the risk of an immune response against the recombinant enzyme, clinical trials have shown prolonged survival and better quality of life in early-onset patients especially when treatment is initiated very early in life. 13 Although enzyme replacement therapy appears to be well tolerated by patients with late-onset Pompe disease, 14 the benefits of treatment are maximized only when initiated before irreversible symptoms develop. 15 The availability of a newborn screening test, a treatment option, and evidence that early treatment improves outcomes led to the addition of Pompe disease to the Recommended Uniform Screening Panel in March 2015.…”

Section: Introductionmentioning

confidence: 99%

Moonlighting newborn screening markers: the incidental discovery of a second-tier test for Pompe disease

Tortorelli

Eckerman

Orsini

et al. 2018

Genetics in Medicine

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Very Early Treatment for Infantile-Onset Pompe Disease Contributes to Better Outcomes

Cited by 89 publications

References 28 publications

Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T > G “late-onset” GAA variant

Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T > G “late-onset” GAA variant

Divergent clinical outcomes of alpha-glucosidase enzyme replacement therapy in two siblings with infantile-onset Pompe disease treated in the symptomatic or pre-symptomatic state

Moonlighting newborn screening markers: the incidental discovery of a second-tier test for Pompe disease

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