Case 4 presented with renal and hepatic involvement at 3 months, and case 5 with developmental delay at 7 months. [ajnr.org]

Congenital cardiac defects, ichthyosis, and hypertrichosis may be present. The skin over the dorsum of the hands and feet often appears dark. Ataxia is sometimes present and MRIs may reveal vermal and cerebellar hypoplasia. [disorders.eyes.arizona.edu]

Osteopenia or osteoporosis was present in all patients of our cohort, sometimes with severe clinical implications. [ojrd.biomedcentral.com]

The infantile form is fatal in infancy and presents with hypotonia and a hypertrophic cardiomyopathy (CARDIOMYOPATHY, HYPERTROPHIC). The childhood form usually presents in the second year of life with proximal weakness and respiratory symptoms. [ncbi.nlm.nih.gov]

Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapies. Eur J Pediatr 2003; 162: 359–379. [nature.com]

• Developmental Delay

  61 Berry GT...Morava E 33576051 2021 41 A missense mutation in a patient with developmental delay affects the activity and structure of the hexosamine biosynthetic pathway enzyme AGX1. 61 Chen X...van Aalten DMF 33098688 2021 42 Frequent SLC35A2 brain [malacards.org]

  Definition A disorder characterized by developmental delay, hypotonia, ocular anomalies, and brain malformations. [uniprot.org]

  Systemic Features: Onset of symptoms commonly begins in infancy with severe hypotonia while developmental delays soon become evident as most children do not achieve normal milestones. The amount of cognitive impairment is variable. [disorders.eyes.arizona.edu]

  Symptoms may include neurological problems (developmental delays, cognitive impairment, seizures, ataxia, dysarthria, esotropia), growth problems (failure to thrive, growth delays), organ issues (gastrointestinal symptoms such as diarrhea and vomiting [rarediseasesnetwork.org]

  Symptoms of CDG in infancy and childhood may include: low muscle tone or floppiness (hypotonia) poor growth, failure to thrive developmental delays liver disease (hepatopathy) with elevated liver enzymes abnormal bleeding or blood clotting misaligned [chop.edu]

• Fatigue

  Results: Ischemic forearm exercise resulted in no increase in lactate, an exaggerated increase in ammonia, rapid contractile fatigue and a finger flexor muscle contracture. [n.neurology.org]

  AB - Objective: We investigated metabolism and physiological responses to exercise in an 18-year-old woman with multiple congenital abnormalities and exertional muscle fatigue, tightness, and rhabdomyolysis. [utsouthwestern.influuent.utsystem.edu]

  […] dehydrogenase : 11p15 Differential diagnosis of exercise intolerance CPT II deficiency Most common cause of recurrent myoglobinuria Myoglobinuria occurs after moderate exercise or prolonged fasting Mitochondrial disorders Complex III, or I or IV Premature fatigue [neuromuscular.wustl.edu]

  • Excepting debrancher deficiency (glycogen storage type III, GSD III), defects of glycogen breakdown cause exercise intolerance with premature fatigue, cramps, and myalgia, often culminating in acute muscle breakdown with discoloration of urine (myoglobinuria [medlink.com]

  Clinical features may include hepatomegaly, hypoglycemia, muscle cramps, exercise intolerance, and progressive fatigue and weakness. Preliminary biochemical testing may be helpful in making a diagnosis. [sjhbangorlab.testcatalog.org]

• Short Stature

  stature, craniofacial dysmorphism, with or without congenital heart defects (JDSCD), B3GAT3-congenital disorder of glycosylation (B3GAT3-CDG) Peters-plus syndrome, B3GLCT-congenital disorder of glycosylation (B3GLCT-CDG) B4GALNT1-congenital disorder [invitae.com]

  Long-term complications include gout, hepatic adenomas, osteoporosis, renal disease, and short stature. Major progress has been made in managing this disorder. [ommbid.mhmedical.com]

  stature and limb anomalies 130070 B4GALT7-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies, Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies) Tags Green Green List (high evidence) CCDC115 [panelapp.genomicsengland.co.uk]

  The skeletal system shows obvious signs of delayed or abnormal development, manifested as short stature and short limbs (short-limb dwarfism) as well as broad hands. [tandfonline.com]

• Falling

  Comparable to patients with McArdle disease, the patient developed a 'second wind' with a spontaneous fall in exercise heart rate and perceived exertion. Like in McArdle disease, this was attributable to an increase in muscle oxidative capacity. [utsouthwestern.influuent.utsystem.edu]

  Cycle exercise revealed low oxidative capacity and a spontaneous "second wind," associated with a 40 beat per minute (bpm) drop in exercise heart rate, from 159 (between minute 5-6) to 119 bpm at minute 14 of sustained exercise with a corresponding fall [n.neurology.org]

  The clinical manifestations fall into two groups, those associated with abnormalities of liver function and those involving abnormalities of muscle function. [britannica.com]

  Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below. [invitae.com]

• Pathologist

  Contact 855-516-8404. � Interpretation of this test should be performed in the context of the patient's clinical history and other diagnostic tests by a qualified pathologist. [mayomedicallaboratories.com]

  Assay Assay and technical information Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication [invitae.com]

  Pediatricians, neurologists, surgeons, cardiologists, speech pathologists, ophthalmologists, gastroenterologists and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. [rarediseases.org]

• Tachycardia

  Midgley et al.9 reported a case of fetal tachycardia treated with flecainide. When the fetal hydrops resolved, the mirror syndrome improved. Pirhonen and Hartgill10 reported on a twin pregnancy with one hydropic fetus and one mirror syndrome. [nature.com]

  Shoulder abduction: May be asymmetric Elbow flexion & extension Abdominal muscles Foot dorsiflexion Scapular winging : Mild; May be asymmetric Respiratory: Mild Face & Eyes: Normal Course: Slow progression Cardiomyopathy: Some patients; Ventricular tachycardia [neuromuscular.wustl.edu]

• Cutis Laxa

  laxa (GILPC, ATP6AP2-CDG) ATP6V0A2-congenital disorder of glycosylation (Cutis laxa type 2A) (ATP6V0A2-CDG, ARCL2A) Epileptic encephalopathy of childhood onset (EEOC), ATP6V1A-congenital disorder of glycosylation (Cutis laxa type 2D) (ATP6V1A-CDG, ARCL2D [invitae.com]

  Metabolic cutis laxa syndromes. J Inherit Metab Dis 2011;34:907-16. 50. Morava E, Lefeber DJ, Urban Z, de Meirleir L, Meinecke P, Gillessen Kaesbach G, et al. [biochemia-medica.com]

  laxa, autosomal recessive, type IIA 21920 Wrinkly skin syndrome 278250 V0 subunit A2 of vesicular H(+)-ATPase deficiency (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies) Tags Green Green List (high evidence [panelapp.genomicsengland.co.uk]

  laxa, hypohidrosis Skeletal dysplasia, dysmorphic features, elevated CK Transferrin profiling with APO-CIII profiling Galactose 1.5–2.5 g/kg/day (max 50 g) for endocrinopathy and coagulopathy GPI anchor disorder PIGA-CDG PIGA deficiency XL 300868 Seizures [ncbi.nlm.nih.gov]

  Volume Anomalies Myelinization Disorders Venous Sinus Thrombosis Pachygyria Polymicrogyria Lissencephaly Cortical Dysplasia, Heterotopia Corpus Callosum (CC) Anomalies Pontocerebellar Hypoplasia Nrain Atrophy Ventriculomegaly and Hydrocephaly ATP6V0A2/Cutis [mdpi.com]

• Muscle Contracture

  contractures and rhabdomyolysis in a young woman. [n.neurology.org]

  Prolonged muscle spasm (muscle contracture) is not uncommon and can lead to RM. [ojrd.biomedcentral.com]

The diagnostic workup excluded rhesus incompatibility, viral and autoimmune diseases. After 36 weeks of gestation, the male baby was born via cesarean section. [nature.com]

Conclusion We confirm that CDG screening should be a part of the routine workup of adolescent/adult patients with sporadic or presumably autosomal recessive cerebellar ataxia, even in the absence of other suggestive signs. [ojrd.biomedcentral.com]

• Neutropenia

  Annals of Internal Medicine 116(11): 896-900, 1992 Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: results of the European Study on Glycogen Storage Disease type I. [eurekamag.com]

  […] glycosylation (GORAB-CDG) Myoclonic epilepsy, GOSR2-congenital disorder of glycosylation (GOSR2-CDG) GPAA1-congenital disorder of glycosylation (GPAA1-CDG) Muscular dystrophy-dystroglycanopathy type A7 and type C7 (MDDGA7, MDDGC7) Severe congenital neutropenia [invitae.com]

  A variant caused by a defect in the transport of glucose 6-phosphate (type Ib) (MIM 232200) has the additional findings of neutropenia and impaired neutrophil function, resulting in recurrent bacterial infections and oral and intestinal mucosa ulceration [ommbid.mhmedical.com]

  Curr Mol Med 2:101–227 Google Scholar Chou JY, Jun HS, Mansfield BC (2010) Neutropenia in type Ib glycogen storage disease. [link.springer.com]

  severe congenital 4, autosomal recessive OMIM:612541 autosomal recessive severe congenital neutropenia due to G6PC3 deficiency MONDO:0012930 Tags Q2_21_rating Amber Amber List (moderate evidence) GORAB 3 reviews 2 green 1 red BIALLELIC, autosomal or [panelapp.genomicsengland.co.uk]

• Liver Enzymes Abnormal

  Symptoms of CDG in infancy and childhood may include: low muscle tone or floppiness (hypotonia) poor growth, failure to thrive developmental delays liver disease (hepatopathy) with elevated liver enzymes abnormal bleeding or blood clotting misaligned [chop.edu]

Significant updates on bariatric surgery, Barrett's esophagus, endoscopic ultrasound, endosonography, treatment of liver disease, and much more keep you current on the latest advances. [books.google.de]

Most will need a team of medical specialists to monitor their health over time and adjust needed treatments. [chop.edu]

Treatment and prognosis Although there is currently no cure for CDG, there are many treatments and therapies available. The goal of these treatments is to treat the symptoms and the problems caused by the condition. [rarediseasesnetwork.org]

Treatment and prognosis Although there is currently no cure for CDG, there are many treatments and therapies available. The goal of these treatments is to treat the symptoms and the problems caused by the condition. [rarediseasesnetwork.org]

Prognosis is good; adult patients have normal stature and minimal hepatomegaly. [ommbid.mhmedical.com]

Identification of a pathogenic variant may assist with prognosis, clinical management, familial screening, and genetic counseling. [mayomedicallaboratories.com]

Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. [rarediseases.org]

PMID: 20531024 Prognosis Magoulas PL, El-Hattab AW, Roy A, Bali DS, Finegold MJ, Craigen WJ Hum Pathol 2012 Jun;43(6):943-51. Epub 2012 Feb 2 doi: 10.1016/j.humpath.2011.10.001. [ncbi.nlm.nih.gov]

Etiology The etiology of GSD is best understood by following the metabolic events leading to the synthesis (glycogenesis) and degradation of glycogen (glycogenolysis). [knowledge.statpearls.com]

They are organised into groups, and further divided into clinical, etiological or histopathological sub-types. [orpha.net]

The diagnosis of CDGs should be suspected in cases with neurological signs and symptoms of unknown etiology, or in any patient with multisystemic disease even in the absence of neurological features. [clinicaltrials.gov]

Localization myopathic GSD cardiac GSD hepatic GSD Etiology GSD MIM. Deficiency Eponym Gene MIM. [humpath.com]

Etiology JAMA Neurol 2014 Jan;71(1):41-7. doi: 10.1001/jamaneurol.2013.4888. [ncbi.nlm.nih.gov]

Discussions focus on epidemiological studies of diabetes and atherosclerosis, overt diabetes mellitus, and effects of selection, age, obesity, and other factors. [books.google.com]

Epidemiological Studies of Diabetes and Atherosclerosis VII. Discussion References Chapter 11. Insulin Antagonists and Disturbances in Carbohydrate Metabolism I. Introduction II. Regulation of Circulating Insulin Activity III. [elsevier.com]

2 : Xq24 Phosphorylase (McArdle's), severe phenotype: 11q13 Triosephosphate isomerase : 12p13 Acid Maltase Deficiency (Glycogen storage disease 2 (GSD2); Pompe disease) ● Acid α-1,4-glucosidase (GAA) ; Chromosome 17q25.3; Recessive Nosology: LGMD 2V Epidemiology [neuromuscular.wustl.edu]

Relevant External Links for PGM1 Genetic Association Database (GAD) PGM1 Human Genome Epidemiology (HuGE) Navigator PGM1 Atlas of Genetics and Cytogenetics in Oncology and Haematology: PGM1 No data available for Genatlas for PGM1 Gene Phosphoglucomutase [genecards.org]

Epidemiology The overall incidence of GSD (all forms) in Europe, Canada, and the United States is estimated to be between 1 in 20,000 and 1 in 40,000. [knowledge.statpearls.com]

[…] disorders or settings where the test may be helpful Aids in the identification of monocytic differentiation Aids in phenotyping hematolymphoid neoplasms that are suspected to represent histiocytic sarcomas Clinical Information Discusses physiology, pathophysiology [mayomedicallaboratories.com]

The underlying pathophysiology of this ‘mirroring’ of the fetal hydrops in the mother still remains unclear. [nature.com]

Pathophysiology Figure 1 summarizes the pathophysiology for each GSD, along with organ(s) affected, as well as the potential signs. In general, GSDs primarily affect the liver, skeletal muscle, or both. [knowledge.statpearls.com]

PIGS-associated early onset epileptic developmental encephalopathy. 61 Efthymiou S...Houlden H 33410539 2021 37 Deciphering the premature mortality in PIGA-CDG - An untold story. 61 Bayat A...Moller RS 33508693 2021 38 N-Glycan Modification in Covid-19 Pathophysiology [malacards.org]

A common pathophysiologic feature of glycogenosis types III, V and VII. N Engl J Med 317: 75–80 PubMed CrossRef Google Scholar 5. Fox IH, Palella TD, Kelley WN (1987) Hyperuricemia: a marker for cell energy crisis. [link.springer.com]

In skeletal muscle, e.g., GSD 5, this can prevent proper muscle functioning, exercise intolerance and rhabdomyolysis. [knowledge.statpearls.com]

A high-protein diet may also be effective in preventing hypoglycemia as gluconeogenesis is intact in these patients. Currently, there is no effective treatment for the progressive myopathy or cardiomyopathy. [ommbid.mhmedical.com]

This has been mentioned in other samples of adult PMM2-CDG patients [16],[23] and implies the importance of specific monitoring to prevent fractures. [ojrd.biomedcentral.com]

Just as cells reciprocally regulate glycolysis and gluconeogenesis to prevent a futile cycle, so too do cells use reciprocal schemes to regulate glycogen breakdown and synthesis. [oregonstate.edu]

Treatment for GSDs, in the form of frequent carbohydrate dosing is available for some of the GSDs and functions to prevent the use of the endogenous glycogen catabolic pathway. [invitae.com]