Presentation
The phenotypic spectrum is broad, both within and between types, with reported clinical presentations ranging from isolated developmental delay to multisystem manifestations [11,12]. Most patients present with neurologic findings. [medilib.ir]
Osteopenia or osteoporosis was present in all patients of our cohort, sometimes with severe clinical implications. [ojrd.biomedcentral.com]
Affected individuals may also present with eye, skin, and cardiac disease, as well as facial dysmorphisms. [atm.amegroups.com]
Case presentation The patient was a 17-month-old boy who weighed 6.5 kg and was 71 cm tall. He presented for strabismus surgery. [jaclinicalreports.springeropen.com]
Entire Body System
- Weakness
As an example, infants with mitochondrial disease may have hypotonia, advancing muscle weakness, and cardiomyopathy while children with CDG may have hypotonia and pericardial effusion. [medilib.ir]
ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies. J Inherit Metab Dis 2016;39(5):713-23. PMID 27287710 44 Morava E, Vodopiutz J, Lefeber DJ, et al. [medlink.com]
Additional symptoms include various abnormalities of the kidneys, liver and heart; skeletal abnormalities including bony overgrowth or deformities; abnormalities of muscle fibers that can cause pain and weakness (myopathy); skin changes such as scaly [rarediseases.org]
ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies. J Inherit Metab Dis. 2016;39:713–23. [ncbi.nlm.nih.gov]
To date a single patient with CDG-Io has been identified who presented at age 11 with symptoms of dilated cardiomyopathy, muscle weakness, and an unsteady gait. [themedicalbiochemistrypage.org]
- Anemia
●In CAD-CDG (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase), two persons had cessation of seizures and improvement in development and anemia on uridine supplementation [32]. [medilib.ir]
La talasemia mayor se asocia con esplenomegalia y anemia. [genaden.com]
Their symptoms included moderate hepatomegaly, PLE (see CDG-Ib), hypotonia, lung hypoplasia, anemia, and thrombocytopenia. All but one of the observed patients succumbed the the disorder within the first year of life. [themedicalbiochemistrypage.org]
Cardiomyopathy, congenital structural heart defects All findings seen in N-linked pathway possible, isolated polycystic liver disease, high cholesterol, cholestatic liver disease, IUGR Isolated leukocyte adhesion deficiency, isolated congenital dyserythropoietic anemia [ncbi.nlm.nih.gov]
Gastrointestinal
- Failure to Thrive
Some people have severe developmental delay, failure to thrive, and multiple organ problems, while others have diarrhea, low blood sugar (hypoglycemia), liver problems, and normal developmental potential. [rareguru.com]
Infantile presentation includes developmental delay, failure to thrive, hepatopathy, hypotonia, hypoglycemia, protein-losing enteropathy, immunologic findings, and skin, eye, and skeletal findings. Most infants do not require hospitalization. [medilib.ir]
Additionally, these individuals have severe failure to thrive after birth. [themedicalbiochemistrypage.org]
Constitutionally, patients commonly have failure to thrive due to feeding and GI abnormalities and global developmental delay. [atm.amegroups.com]
Skin
- Cutis Laxa
Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2. Nat Genet 2008;40:32-4.** PMID 18157129 33 Kranz C, Denecke J, Lehle L, et al. [medlink.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]
"Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2". Nat. Genet. 40: 32–4. ↑ Amberger J, Bocchini C, Hamosh A. (2011). [wikidoc.org]
FBLN5 Cutis laxa autosómica recesiva, tipo IA AR DESCRIPCIÓN Cutis laxa autosómica recesiva, tipo IA: Anim pariatur cliche reprehenderit, enim eiusmod high life accusamus terry richardson ad squid. [genaden.com]
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]
Neurologic
- Ataxia
Usual rating scales of ataxia, such as the Scale for the Assessment and Rating of Ataxia, could not be used with the 13 patients reexamined for this study because of their marked slowness and difficulties with comprehension. [ojrd.biomedcentral.com]
[…] nipples, fat pads, contractures, arachnodactyly a.o.), microcephaly (mostly neonatal), intractable seizures (with neonatal or later onset), visual disturbances (strabismus, nystagmus, retinopathy and/or (in some patients) severe visual loss), tremor, ataxia [nature.com]
Cerebellar ataxia and congenital disorder of glycosylation Ia (CDG-Ia) with normal routine CDG screening. J Neurol 2007;254:1356-8. PMID 17694350 65 Winawer MR, Griffin NG, Samanamud J, et al. [medlink.com]
•Children – In childhood, developmental issues continue with neurologic signs of cognitive impairment, hypotonia, seizures, ataxia, dysarthria, and dysmetria. Hepatopathy stabilizes, although coagulopathy continues. [medilib.ir]
Cerebellar ataxia is an increasingly recognized symptom along with multisystemic involvement (38-40). [ncbi.nlm.nih.gov]
- Cerebellar Ataxia
PMM2-CDG in adolescence and adulthood It has been reported repeatedly that cerebellar ataxia is not progressive in PMM2-CDG [13],[23], which we observed in our cohort. [ojrd.biomedcentral.com]
Cerebellar ataxia and congenital disorder of glycosylation Ia (CDG-Ia) with normal routine CDG screening. J Neurol 2007;254:1356-8. PMID 17694350 65 Winawer MR, Griffin NG, Samanamud J, et al. [medlink.com]
Cerebellar ataxia is an increasingly recognized symptom along with multisystemic involvement (38-40). [atm.amegroups.com]
- Apraxia
Schöls L, Sequeiros J, Goizet C, Marelli C, Le Ber I, Koht J, Gazulla J, De Bleecker J, Mukhtar M, Drouot N, Ali-Pacha L, Benhassine T, Chbicheb M, M’Zahem A, Hamri A, Chabrol B, Pouget J, Murphy R, Watanabe M, Coutinho P, et al: Ataxia with oculomotor apraxia [ojrd.biomedcentral.com]
APTX Ataxia con apraxia oculomotora e hipoalbuminemia de inicio temprano AR DESCRIPCIÓN Ataxia con apraxia oculomotora e hipoalbuminemia de inicio temprano: Anim pariatur cliche reprehenderit, enim eiusmod high life accusamus terry richardson ad squid [genaden.com]
- Dysarthria
•Children – In childhood, developmental issues continue with neurologic signs of cognitive impairment, hypotonia, seizures, ataxia, dysarthria, and dysmetria. Hepatopathy stabilizes, although coagulopathy continues. [medilib.ir]
Treatment Neurologic Ophthalmologic Cardiologic Gastroenterological Hematologic Renal Endocrine Dermatologic Musculoskeletal/other N-linked glycosylation PMM2-CDG CDG type Ia AR 212065 ID (except MPI), DD, seizures (50%), hypotonia, ataxia, dysmetria, dysarthria [ncbi.nlm.nih.gov]
Workup
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]
X-Ray
- Pericardial Effusion
pericardial effusion, oedema, hepatomegaly, cholestatic jaundice, portal hypertension, Budd–Chiari syndrome, nephrotic syndrome, spontaneous haemorrhage and venous thrombosis. [nature.com]
As an example, infants with mitochondrial disease may have hypotonia, advancing muscle weakness, and cardiomyopathy while children with CDG may have hypotonia and pericardial effusion. [medilib.ir]
Fluid accumulation around the lungs or heart (pleural or pericardial effusions) has also been reported. [rarediseases.org]
Infants may also have hepatic disease, nephrotic syndrome and renal cysts, pericardial effusion and hypertrophic cardiomyopathy, failure to thrive, and multi-organ failure resulting in death within the first year of life in up to 20% of affected individuals [ncbi.nlm.nih.gov]
Serum
- Hypogammaglobulinemia
Glycosylation, hypogammaglobulinemia, and resistance to viral infections. N Engl J Med. 2014;370(17):1615–25. [PMC free article: PMC4066413] [PubMed: 24716661] Sanz-Nebot V, Balaguer E, Benavente F, Neusub C, Barbosa J. [ncbi.nlm.nih.gov]
Expanding spectrum of congenital disorder of glycosylation Ig (CDG-Ig): sibs with a unique skeletal dysplasia, hypogammaglobulinemia, cardiomyopathy, genital malformations, and early lethality. Am J Med Genet A 2007;143A:1371-8. 37. [biochemia-medica.com]
- Erythroblast
Carbohydrate-deficient glycoprotein syndrome type II: an autosomal recessive N-acetylglucosaminyltransferase II deficiency different from typical hereditary erythroblastic multinuclearity, with a positive acidified-serum lysis test (HEMPAS). [medlink.com]
Treatment
All diagnostic endeavors are followed by the quest for a reliable treatment. The isolated success of CDG-Ib treatment will be described with the hope that this may expand to other type I CDG disorders. [go.gale.com]
Treatment for glycosylation defects is mainly supportive, although targeted therapies are available for MPI-CDG, SLC35C1-CDG, PIGM-CDG, and PGM1-CDG. Details about these treatments are under the “Targeted Therapies and Prognosis” section below. [atm.amegroups.com]
Ketogenic diet - A novel treatment for early epileptic encephalopathy due to PIGA deficiency. [ncbi.nlm.nih.gov]
Standard Therapies Treatment The treatment of most forms of CDG is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]
Prognosis
The various types of CDG often have different symptoms and a different prognosis. Even individuals with the same type of CDG may not have the same symptoms and prognosis. [rareguru.com]
Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. [rarediseases.org]
Details about these treatments are under the “Targeted Therapies and Prognosis” section below. [atm.amegroups.com]
[…] microcysts with follow-up as indicated ●Ophthalmologic examination for evaluation of lens, retina, ocular mobility, and intraocular pressure ●Clinical genetics evaluation to discuss the hereditary component of CDGs and updates learned about the disorder PROGNOSIS [medilib.ir]
Etiology
Clinical features and genetic etiology of more common CDG by pathway is summarized in Table S1. [atm.amegroups.com]
In addition, several CDGs of so far unknown etiology (CDG-x) have been recognized. [biochemia-medica.com]
Epidemiology
EPIDEMIOLOGY — The prevalence and incidence of CDGs as a group have not been established [2]. [medilib.ir]
Epidemiology The incidence and prevalence of all types of CDG in aggregate have not been well established, although patients have been reported worldwide from almost every ethnic background and both sexes are equally affected. [atm.amegroups.com]
Pathophysiology
The pathophysiology results from depressed synthesis or remodeling of oligosaccharide moieties of glycoproteins. The ultimate result is the formation of abnormal glycoproteins affecting their structure and metabolic functions. [go.gale.com]
Although the pathophysiology of multitude symptoms remains to be elucidated, the relationship between certain glycosylation pathways and specific clinical symptoms has been clarified. [atm.amegroups.com]
Respiratory complications in the postanesthesia care unit: a review of pathophysiological mechanisms. Can J Respir Ther. 2013;49(4):21–9. Google Scholar Download references Acknowledgements Nothing. [jaclinicalreports.springeropen.com]
Prevention
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]
The MPDU1 gene was identified on the basis of the fact that it could rescue defects in Chinese hamster ovary (CHO) cells that prevented the synthesis and utilization of Dol-P-Man. [themedicalbiochemistrypage.org]
In gene therapy, the defective gene present in a patient is replaced with a normal gene to enable the production of the active enzyme and prevent the development and progression of the disease. [rarediseases.org]
For example, N-acetylgalactosaminyltransferase 3 (GALNT3) O-glycosylates the phosphaturic hormone, FGF23, preventing proteolytic cleavage and allowing its intact secretion. [atm.amegroups.com]