Original ArticleDefining the Phenotype and Assessing Severity in Phosphoglucomutase-1 Deficiency
Section snippets
Methods
We evaluated 27 patients (18 children and 9 adults) with confirmed diagnosis of PGM1-CDG. The diagnosis was based on enzyme and molecular analysis. Patient age ranged from 2 to 43 years at the time of assessment, with 17 male and 10 female patients in the cohort. None of the patients exhibited severe motor or cognitive impairment. We obtained patient data by using a specific survey on informed consent (institutional review board reference #13-533377) and collected data on clinical features,
Results
Although the majority of the patients have been reported previously,4, 8, 12 we recruited 6 new patients, 5 with novel PGM1 mutations (patient 5, 7, 11, 14, and 17) and 1 with a previously reported mutation (patient 27).4 There was a great diversity in the phenotypic spectrum. Hepatopathy is the most frequent clinical manifestation in the cohort (100%), followed by hypoglycemia (89%), congenital malformation (85%), and growth retardation (85%). The type and frequency of congenital malformation
Discussion
Although our patient cohort is small (n = 27), we demonstrated that by assessing the presence and absence of congenital malformation and dilated cardiomyopathy, 2 of the most common clinical features that are consequences of in utero developmental anomaly, we were able to classify the patients into 3 phenotypic groups; mild, moderate, and severe. Furthermore, we proved that our classification approach is clinically and statistically meaningful by using TPCRS, a simple screening tool we tailored
References (36)
Galactose supplementation in phosphoglucomutase-1 deficiency; review and outlook for a novel treatable CDG
Mol Genet Metab
(2014)- et al.
Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency
J Biol Chem
(2014) Introduction to principal components analysis
PM R
(2014)- et al.
Residual α-L-iduronidase activity in fibroblasts of mild to severe Mucopolysaccharidosis type I patients
Mol Genet Metab
(2013) - et al.
Molecular identification of mammalian phosphopentomutase and glucose-1,6-bisphosphate synthase, two members of the alpha-D-phosphohexomutase family
J Biol Chem
(2007) - et al.
Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction
J Am Coll Cardiol
(2003) - et al.
Re-Evaluating “Transitional Neonatal Hypoglycemia”: Mechanism and Implications for Management
J Pediatr
(2015) - et al.
Neonatal hypoglycemia—answers, but more questions
J Pediatr
(2012) - et al.
Congenital disorders of glycosylation: sweet news
Curr Opin Pediatr
(2011) - et al.
Perinatal and early infantile symptoms in congenital disorders of glycosylation
Am J Med Genet A
(2013)
Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing
Hum Mol Genet
Multiple phenotypes in phosphoglucomutase 1 deficiency
N Engl J Med
Muscle glycogenosis due to phosphoglucomutase 1 deficiency
N Engl J Med
Skeletal muscle glycogenosis: an investigation of two dissimilar cases
J Neurol Neurosurg Psychiatry
A novel congenital disorder of glycosylation type without central nervous system involvement caused by mutations in the phosphoglucomutase 1 gene
J Inherit Metab Dis
Mutations in hereditary phosphoglucomutase 1 deficiency map to key regions of enzyme structure and function
J Inherit Metab Dis
Nijmegen paediatric CDG rating scale: a novel tool to assess disease progression
J Inherit Metab Dis
Glycogen storage disease-like phenotype with central nervous system involvement in a PGM1-CDG patient
Neuro Endocrinol Lett
Cited by (42)
Galactose in human metabolism, glycosylation and congenital metabolic diseases: Time for a closer look
2021, Biochimica et Biophysica Acta - General SubjectsCongenital disorders of glycosylation in children – Histopathological and ultrastructural changes in the liver
2021, Pediatrics and NeonatologyFetal glycosylation defect due to ALG3 and COG5 variants detected via amniocentesis: Complex glycosylation defect with embryonic lethal phenotype
2020, Molecular Genetics and MetabolismPhosphoglucomutase-1 deficiency: Early presentation, metabolic management and detection in neonatal blood spots
2020, Molecular Genetics and MetabolismCitation Excerpt :To compare the description of early presentation with literature and to identify possible age-related clinical presentations of PGM1 deficiency, we performed a systematic literature review on clinical symptoms in PGM1-CDG. The systematic review of the literature led to 198 papers (Table S2), of which 17 case reports were included [1,4–6,8,11,16,21–31]. The article by Radenkovic et al. [12] was also included despite being a review as it provided unreported clinical details on previously published patients, with particular attention for CNS symptoms.
The congenital disorder of glycosylation in PGM1 (PGM1-CDG) can cause severe cardiomyopathy and unexpected sudden cardiac death in childhood
2019, Forensic Science International: Genetics
Supported by the National Institute of General Medical Sciences of the National Institutes of Health (1 U54 GM104940), which funds the Louisiana Clinical and Translational Science Center. T.H. is supported by General University Hospital in Prague, Czech Republic (RVO-VFN 64165), and the Ministry of Health of the Czech Republic (MZ CR AZV 16-31932A). The authors declare no conflicts of interest.