Clinical Variability in 2 Siblings With Late-Onset Pompe Disease

Correia, Carolina da Cunha; Fontana, Pedro Nogueira; Góes, Gustavo; Zanoteli, Edmar

doi:10.1097/cnd.0000000000000216

Cited by 2 publications

(2 citation statements)

References 5 publications

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“…Limited information is available for the older sibling. The disease progression of these patients is of interest because the disease is progressing differently for these siblings despite the same genotype and a similar environment [72][73][74].…”

Section: Discussionmentioning

confidence: 99%

The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease

Bevilacqua

Ehuletche²,

Perna

et al. 2020

Orphanet J Rare Dis

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Background: Limb-girdle muscular dystrophy (LGMD) is a group of neuromuscular disorders of heterogeneous genetic etiology with more than 30 directly related genes. LGMD is characterized by progressive muscle weakness involving the shoulder and pelvic girdles. An important differential diagnosis among patients presenting with proximal muscle weakness (PMW) is late-onset Pompe disease (LOPD), a rare neuromuscular glycogen storage disorder, which often presents with early respiratory insufficiency in addition to PMW. Patients with PMW, with or without respiratory symptoms, were included in this study of Latin American patients to evaluate the profile of variants for the included genes related to LGMD recessive (R) and LOPD and the frequency of variants in each gene among this patient population. Results: Over 20 institutions across Latin America (Brazil, Argentina, Peru, Ecuador, Mexico, and Chile) enrolled 2103 individuals during 2016 and 2017. Nine autosomal recessive LGMDs and Pompe disease were investigated in a 10gene panel (ANO5, CAPN3, DYSF, FKRP, GAA, SGCA, SGCB, SGCD, SGCG, TCAP) based on reported disease frequency in Latin America. Sequencing was performed with Illumina's NextSeq500 and variants were classified according to ACMG guidelines; pathogenic and likely pathogenic were treated as one category (P) and variants of unknown significance (VUS) are described. Genetic variants were identified in 55.8% of patients, with 16% receiving a definitive molecular diagnosis; 39.8% had VUS. Nine patients were identified with Pompe disease. Conclusions: The results demonstrate the effectiveness of this targeted genetic panel and the importance of including Pompe disease in the differential diagnosis for patients presenting with PMW.

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Section: Discussionmentioning

confidence: 99%

The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease

Bevilacqua

Ehuletche²,

Perna

et al. 2020

Orphanet J Rare Dis

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show abstract

“…22 The likely cause of this condition is considered to be the modifying effect of in-gene or out-gene variants. 23,24 Besides the severity of the mutation, the course of PD is variable due to CRIM status and residual GAA enzymatic activity in muscles. 5,25 Different disease phenotypes are related to the levels of residual GAA enzymatic activity in muscles; less than 3% of normal enzymatic activity is found in severe infantile cases, and residual levels ranging 3 to 30% of normal are found in less severe late-onset forms.…”

Section: Discussionmentioning

confidence: 99%

A Newborn with Infantile-Onset Pompe Disease Improving after Administration of Enzyme Replacement Therapy: Case Report

Bor

İlhan

Gümüş

et al. 2020

J Pediatr Intensive Care

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Pompe disease (PD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of acid α-1,4-glucosidase enzyme (GAA). PD has two forms, namely the infantile-onset and the late-onset form. In untreated cases, infantile-onset form usually leads to cardio-respiratory failure and death in the first year of life. Herein, we report a newborn with infantile-onset PD characterized by muscular hypotonia, respiratory distress, hypertrophic cardiomyopathy, hepatomegaly, elevated serum enzyme levels of aspartate aminotransferase of 117 IU/L (three times the normal value), alanine aminotransferase of 66 IU/L (1.8 times the normal value), lactate dehydrogenase of 558 IU/L (1.2 times the normal value), and creatine kinase >5,000 IU/L (16 times the normal value). Dried blood spot testing was performed and revealed decreased GAA enzymatic activity (0.07 nmol/mL/h, normal 0.93–7.33 nmol/mL/h). GAA gene analysis performed for confirming the diagnosis showed homozygous mutation c.896T >C (p.Leu299Pro). Initiation of enzyme replacement therapy (ERT) (ERT; 20 mg/kg, once every week) at 28 days of age resulted in weaning off from respiratory support within 1 week after treatment, normalization of cardiac abnormalities, and normal neuromotor development in the 16th month of age. Early diagnosis and early treatment with ERT, especially in the neonatal period, is of great importance to improve cardiac function and motor development in infantile-onset PD.

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Clinical Variability in 2 Siblings With Late-Onset Pompe Disease

Cited by 2 publications

References 5 publications

The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease

The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease

A Newborn with Infantile-Onset Pompe Disease Improving after Administration of Enzyme Replacement Therapy: Case Report

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