Three cases of multi-generational Pompe disease: Are current practices missing diagnostic and treatment opportunities?

Authors:
Stephanie Austin
Stephanie Austin
Duke University Medical Center
United States
Jennifer Sullivan
Jennifer Sullivan
Vascular Biology Center
Lauren Bailey
Lauren Bailey
University of Tennessee Health Science Center
United States
David Viskochil
David Viskochil
University of Utah
Salt Lake City | United States
Priya S Kishnani
Priya S Kishnani
Duke University Medical Center
United States

Am J Med Genet A 2017 Oct 1;173(10):2628-2634. Epub 2017 Aug 1.

Duke University Medical Center, Durham, North Carolina.

Pompe disease (Glycogen storage disease type II, GSDII, or acid maltase deficiency) is an autosomal recessive metabolic myopathy with a broad clinical spectrum, ranging from infantile to late-onset presentations. In 2015, Pompe disease was added as a core condition to the Recommended Uniform Screening Panel for state newborn screening (NBS). The clinical importance of Pompe disease is evolving with the use of NBS, increasing awareness of the disease, and higher than previously reported disease prevalence; however, current practices miss additional diagnostic and potential treatment opportunities in close relatives of the family proband. In this report, we describe three families with multiple individuals in multiple generations affected by both infantile and late-onset clinical presentations of Pompe disease. The presence of multi-generational disease within these families highlights the importance of subsequent risk assessment through medical history and physical examination, with a low threshold for the screening of a proband's family members. We recommend enzymology (GAA activity assay) as the first screening method, as opposed to targeted mutation analysis, for at-risk family members. Given that the initial symptoms of the slowly progressive late-onset presentation of Pompe disease may be mild or non-specific, enzymatic testing of all parents of affected infants should be considered.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.38369DOI Listing
October 2017
4 Reads

Publication Analysis

Top Keywords

pompe disease
24
disease
10
current practices
8
infantile late-onset
8
family members
8
pompe
6
diagnostic potential
4
targeted mutation
4
potential treatment
4
additional diagnostic
4
practices additional
4
treatment opportunities
4
prevalence current
4
close relatives
4
method opposed
4
proband report
4
report describe
4
family proband
4
relatives family
4
opposed targeted
4

Similar Publications

A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations.

Orphanet J Rare Dis 2012 Jun 7;7:35. Epub 2012 Jun 7.

Center for Pediatric and Adolescent Medicine, University Medical Center, Mainz, Germany.

Background: Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder due to a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1. Read More

View Article
June 2012

Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations.

J Neurol 2009 Nov 9;256(11):1881-90. Epub 2009 Jul 9.

Myopathies and Molecular Biology Group, Department of Neurology, School of Medicine, University of São Paulo, Av Dr Arnaldo, 455, 4th Floor, Room 4110, São Paulo, SP 01246-903, Brazil.

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening. Read More

View Article
November 2009

Development of a clinical assay for detection of GAA mutations and characterization of the GAA mutation spectrum in a Canadian cohort of individuals with glycogen storage disease, type II.

Mol Genet Metab 2007 Dec 27;92(4):325-35. Epub 2007 Aug 27.

Children's Hospital of Eastern Ontario, Canada K1H 8L1.

Glycogen storage disease, type II (GSDII; Pompe disease; acid maltase deficiency) is an autosomal recessive disease caused by mutations of the GAA gene that lead to deficient acid alpha-glucosidase enzyme activity and accumulation of lysosomal glycogen. Although measurement of acid alpha-glucosidase enzyme activity in fibroblasts remains the gold standard for the diagnosis of GSDII, analysis of the GAA gene allows confirmation of clinical or biochemical diagnoses and permits predictive and prenatal testing of individuals at risk of developing GSDII. We have developed a clinical molecular test for the detection of GAA mutations based on cycle sequencing of the complete coding region. Read More

View Article
December 2007

Broad spectrum of Pompe disease in patients with the same c.-32-13T->G haplotype.

Neurology 2007 Jan;68(2):110-5

Department of Clinical Genetics, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, the Netherlands.

Background: Pompe disease (acid maltase deficiency, glycogen storage disease type II; OMIM 232300) is an autosomal recessive lysosomal storage disorder characterized by acid alpha-glucosidase deficiency due to mutations in the GAA gene. Progressive skeletal muscle weakness affects motor and respiratory functions and is typical for all forms of Pompe disease. Cardiac hypertrophy is an additional fatal symptom in the classic infantile subtype. Read More

View Article
January 2007