Clinical and Genetic Aspects of Juvenile Onset Pompe Disease
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Clinical and Genetic Aspects of Juvenile Onset Pompe Disease. / Holzwarth, Johanna; Minopoli, Nadja; Pfrimmer, Charlotte; Smitka, Martin; Borrel, Sabine; Kirschner, Janbernd; Muschol, Nicole; Hartmann, Hans; Hennermann, Julia B; Neubauer, Bernd A; Hobbiebrunken, Elke; Husain, Ralf; Hahn, Andreas.
In: NEUROPEDIATRICS, Vol. 53, No. 1, 02.2022, p. 39-45.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Clinical and Genetic Aspects of Juvenile Onset Pompe Disease
AU - Holzwarth, Johanna
AU - Minopoli, Nadja
AU - Pfrimmer, Charlotte
AU - Smitka, Martin
AU - Borrel, Sabine
AU - Kirschner, Janbernd
AU - Muschol, Nicole
AU - Hartmann, Hans
AU - Hennermann, Julia B
AU - Neubauer, Bernd A
AU - Hobbiebrunken, Elke
AU - Husain, Ralf
AU - Hahn, Andreas
N1 - Thieme. All rights reserved.
PY - 2022/2
Y1 - 2022/2
N2 - Little is known about clinical symptomatology and genetics of juvenile onset Pompe disease (JOPD). The aims of this study were to analyze how these children are diagnosed, what clinical problems they have, and how phenotype is related to genotype. To accomplish this, we analyzed retrospectively data of 34 patients diagnosed after their first and before completion of their 18th birthday. Median age at diagnosis was 3.9 (range 1.1-17) years. Eight patients (23.5%) developed initial symptoms in the first year, 12 (35%) between 1 and 7 years, and 6 (18%) thereafter. Eight (23.5%) had no clinical symptoms at the time of diagnosis. Indications for diagnostics were a positive family history in three (9%), hyperCKemia in eight (23.5%), motor developmental delay in three (9%), and muscle weakness and/or pain in 17 (50%). Rare clinical signs were failure to thrive, recurrent diarrhea, and suspected hepatopathy with glycogen storage. Thirty-two different mutations were identified. Twenty-seven patients (79.5%) carried the milder c.32-13T > G mutation, known to be associated with a broad range of phenotypes. Three out of eight patients manifesting within the first year of life showed generalized muscle weakness, hypertrophic cardiomyopathy, and had to be ventilated during the course of disease, thereby demonstrating clinical overlap with infantile onset Pompe disease.These findings demonstrate that the phenotype of JOPD is broad and that the differential is not only restricted to neuromuscular disorders. Genotypic analysis was useful to delineate subjects with early onset JOPD from those with IOPD, but overall genotype-phenotype correlation was poor.
AB - Little is known about clinical symptomatology and genetics of juvenile onset Pompe disease (JOPD). The aims of this study were to analyze how these children are diagnosed, what clinical problems they have, and how phenotype is related to genotype. To accomplish this, we analyzed retrospectively data of 34 patients diagnosed after their first and before completion of their 18th birthday. Median age at diagnosis was 3.9 (range 1.1-17) years. Eight patients (23.5%) developed initial symptoms in the first year, 12 (35%) between 1 and 7 years, and 6 (18%) thereafter. Eight (23.5%) had no clinical symptoms at the time of diagnosis. Indications for diagnostics were a positive family history in three (9%), hyperCKemia in eight (23.5%), motor developmental delay in three (9%), and muscle weakness and/or pain in 17 (50%). Rare clinical signs were failure to thrive, recurrent diarrhea, and suspected hepatopathy with glycogen storage. Thirty-two different mutations were identified. Twenty-seven patients (79.5%) carried the milder c.32-13T > G mutation, known to be associated with a broad range of phenotypes. Three out of eight patients manifesting within the first year of life showed generalized muscle weakness, hypertrophic cardiomyopathy, and had to be ventilated during the course of disease, thereby demonstrating clinical overlap with infantile onset Pompe disease.These findings demonstrate that the phenotype of JOPD is broad and that the differential is not only restricted to neuromuscular disorders. Genotypic analysis was useful to delineate subjects with early onset JOPD from those with IOPD, but overall genotype-phenotype correlation was poor.
U2 - 10.1055/s-0041-1735250
DO - 10.1055/s-0041-1735250
M3 - SCORING: Journal article
C2 - 34852371
VL - 53
SP - 39
EP - 45
JO - NEUROPEDIATRICS
JF - NEUROPEDIATRICS
SN - 0174-304X
IS - 1
ER -