Presentation
The stroke-like event our patient presented with, is reportedly a frequent finding in CDH-1a patients, and is most likely caused by an active epileptic inhibitory process rather than real ischaemia. [4] To summarize, we present a typical case of CDG-1a [eurorad.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]
In contrast, more mildly affected patients may only present with hypotonia and seizures, or behavioral abnormalities and speech disability. [rarediseasesnetwork.org]
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]
Entire Body System
- Developmental Delay
B3GALTL-CDG – Symptoms may include eye problems, developmental delays, facial anomalies and short stature. [chop.edu]
Individuals who are only mildly affected may present with isolated developmental delay, intellectual disability and coagulation abnormalities. [fcdgc.rarediseasesnetwork.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]
Genes related to Dpm1-cdg DPM1 ADNP-AS1 View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Dpm1-cdg Intellectual disability Seizures Global developmental delay Generalized hypotonia Microcephaly Ataxia [mendelian.co]
- Disability
Individuals who are only mildly affected may present with isolated developmental delay, intellectual disability and coagulation abnormalities. [fcdgc.rarediseasesnetwork.org]
In contrast, more mildly affected patients may only present with hypotonia and seizures, or behavioral abnormalities and speech disability. [rarediseasesnetwork.org]
N-linked type II forms of CDG include: MAN1B1-CDG – Symptoms may include intellectual disability, facial anomalies and behavior issues. [chop.edu]
Genes related to Dpm1-cdg DPM1 ADNP-AS1 View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Dpm1-cdg Intellectual disability Seizures Global developmental delay Generalized hypotonia Microcephaly Ataxia [mendelian.co]
However, motor disability may worsen with time and may lead to the loss of independent ambulation and autonomy. [ojrd.biomedcentral.com]
- Feeding Difficulties
The most common CDG type, PMM2-CDG, shows a phenotype of inverted nipples, abnormal fat pads, strabismus, hypotonia and feeding difficulties from a few months of age. [onlinelibrary.wiley.com]
Feeding difficulties can lead to a failure to gain weight and grow slower than normal (failure to thrive). Ocular abnormalities, sensorineural hearing loss, cardiac abnormalities and skeletal dysplasias are possible. [fcdgc.rarediseasesnetwork.org]
Feeding difficulties and intestinal problems (such as protein-losing enteropathy (PLE)), are common in ALG6-CDG, which may lead to a failure to gain weight and grow slower than normal (failure to thrive). [rarediseasesnetwork.org]
GMPPA-CDG – Symptoms may include feeding difficulties and gastrointestinal defects. PGM1-CDG – Symptoms may include muscle weakness, short stature, cleft palate, blood clotting problems and liver disease. [chop.edu]
Feeding difficulties leading to failure to thrive are also common. Failure to thrive is defined as the failure to grow and gain weight as would be expected based upon age and gender. [rarediseases.org]
- Recurrent Infection
Othere more variable clinical features included seizures, hypsarrhythmia, poor feeding, microcephaly, recurrent infections, dysmorphic features, shortened limbs, and coagulation defects. [uniprot.org]
Deficiencies in this transporter result in marked thrombocytopenia and neutropenia as well as recurrent infections. [themedicalbiochemistrypage.org]
Fucose therapy can be beneficial in treating recurrent infections associated with this form of CDG and improving health. However, fucose therapy does not help with other symptoms of this disorder. [rarediseases.org]
A typical feature was recurrent infections with marked leukocytosis. Neutrophils of these patients lack sialyl-Lewis x, a fucose-containing carbohydrate ligand of the selectin family of cell adhesion molecules. [nature.com]
- Inflammation
The recurrent infections are attributed to undetectable sialylated Lewisx on the surface of neutrophils which prevents them from adhering to the endothelium at sites of inflammation. [themedicalbiochemistrypage.org]
Sialyl Lewis antigen, a normal fucose-containing carbohydrate ligand to the selectins known cell adhesion molecules, is crucial for recruitment of neutrophils to any inflammation site. [nature.com]
Liver, Gall & Pancreas
- Hepatomegaly
Both exhibited psychomotor impairment, hypotonia, hepatomegaly, microcephaly, and seizures. [themedicalbiochemistrypage.org]
[…] size table The first report of a patient with CDG-Ih is that of a still-surviving patient, who from infancy had protein-losing enteropathy with bouts of severe diarrhea and threatening dehydration, episodic generalized edema, ascites, hypoalbuminemia, hepatomegaly [nature.com]
Eyes
- Esotropia
Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, peripheral neuropathy (PN), strabismus, nystagmus, optic disc pallor, and reduced rod function on electroretinography. [owlapps.net]
Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic pallor, and reduced rod function on electroretinography.[11] Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic [wikidoc.org]
Patients #11 and #14 had no reported signs suggesting PMM2-CDG during childhood, except patient #11 who had an isolated esotropia starting at two months of age. [ojrd.biomedcentral.com]
Esotropia, long philtrum, large, hypoplastic or dysplastic ears, hypotonic facies, and downslanting palpebral fissures are seen (top row). Profile view shows the prominent chin, which is more pronounced with age (bottom row). [atm.amegroups.com]
Musculoskeletal
- Small Head
DOLK-CDG – Symptoms may include seizures, low muscle tone or floppiness (hypotonia), abnormally small head (microcephaly), scaly skin and failure to thrive. [chop.edu]
Neurologic
- Global Developmental Delay
Genes related to Dpm1-cdg DPM1 ADNP-AS1 View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Dpm1-cdg Intellectual disability Seizures Global developmental delay Generalized hypotonia Microcephaly Ataxia [mendelian.co]
Constitutionally, patients commonly have failure to thrive due to feeding and GI abnormalities and global developmental delay. [atm.amegroups.com]
In NGLY1-CDDG the most common presentation is global developmental delay, hyperkinetic movement disorder, peripheral neuropathy, alacrimia/hypolacrimia [103]. [mdpi.com]
- Dysarthria
Intellectual retardation is often overestimated because of dysarthria and motor difficulties. Psychomotor reeducation might improve quality of life. Similar articles CDG type Ia and congenital cytomegalovirus infection: two coexisting conditions. [pubmed.ncbi.nlm.nih.gov]
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]
- Hyperactivity
In conclusion, congenital disorders of glycosylation should be considered in cases of unexplained behavioral symptoms such as hyperactivity and concentration difficulties and mild neurologic signs. [pubmed.ncbi.nlm.nih.gov]
- Cognitive Disorder
The implications of disordered glycosylation in neural development may be relevant for the development and maintenance of normal cognitive functions. [mdpi.com]
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]
Treatment
Specific treatment is only available for PMI-CDG, namely oral mannose supplementation. Galactose treatment is beneficial for the endocrine, liver and coagulation problems in PGM1-CDG. Citing Literature [onlinelibrary.wiley.com]
Treatment and Prognosis To date, there are no known specific treatment options for ALG12-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. Some ALG12-CDG patients die within the first years of life. [fcdgc.rarediseasesnetwork.org]
Treatment and prognosis To date, there are no known specific treatment options for ALG6-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. [rarediseasesnetwork.org]
Treatment Treatment Options: The administration of caloric supplements through tube feeding may be required to maintain adequate nutrition.Orthopedic deformities can sometimes be corrected surgically. [disorders.eyes.arizona.edu]
It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice. [uniprot.org]
Prognosis
Most diagnosed ALG6-CDG patients are still young, which makes long-term prognosis difficult. Most of the older patients reached puberty, and a few of them reached adulthood. [rarediseasesnetwork.org]
Treatment and Prognosis To date, there are no known specific treatment options for ALG12-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. Some ALG12-CDG patients die within the first years of life. [fcdgc.rarediseasesnetwork.org]
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]
Etiology
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]
Clinical features and genetic etiology of more common CDG by pathway is summarized in Table S1. [atm.amegroups.com]
Prognosis depends on the underlying etiology, which is diverse and includes infections, perinatal events and genetic disorders. [mdpi.com]
Epidemiology
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
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]
Prevention
Treatment is aimed at the management of symptoms and the prevention of complications. Some ALG12-CDG patients die within the first years of life. Mild cases, however, seem to have a good life expectancy. [fcdgc.rarediseasesnetwork.org]
Treatment is aimed at the management of symptoms and the prevention of complications. Most diagnosed ALG6-CDG patients are still young, which makes long-term prognosis difficult. [rarediseasesnetwork.org]
N-linked type I forms of CDG have genetic defects that prevent the oligosaccharide building blocks from attaching to proteins as new proteins are formed. [chop.edu]
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]