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]

Affected individuals may also present with eye, skin, and cardiac disease, as well as facial dysmorphisms. [atm.amegroups.com]

"Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late presentation and literature review". Journal of Inherited Metabolic Disease. 32 Suppl 1: S313-9. doi:10.1007/s10545-009-1262-1. PMID 19757145. [en.wikipedia.org]

Now, some CDG types have been recognized as presenting with ASD [76], with most frequent presented in Table 5. [mdpi.com]

• 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]

  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]

  Constitutionally, patients commonly have failure to thrive due to feeding and GI abnormalities and global developmental delay. [atm.amegroups.com]

  In summary, X-linked PIGA mutations present with ESp with hypsarrhythmia and profound developmental delay. In the severe forms also brain abnormalities (thin corpus callosum and delayed myelination) have been reported [63,64]. 2.1.12. [mdpi.com]

• Feeding Difficulties

  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]

  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]

• Developmental Disorder

  The symptoms are varied and often not specific: They range from serious crises after birth with loss of consciousness, seizures, respiratory disorders, or organ failure, to physical and mental developmental disorders. [heidelberg-university-hospital.com]

  University Medical Center, Nijmegen Phenotypes Developmental and epileptic encephalopathy 15, OMIM:615006 developmental and epileptic encephalopathy, 15, MONDO:0014003 Intellectual developmental disorder, autosomal recessive 12, OMIM:611090 intellectual [panelapp.genomicsengland.co.uk]

• Fever

  In another case, although Ese developed without fever, almost all the subsequent seizures appeared during fever period. In the initial interictal EEG diffuse slow waves with multifocal discharges dominated. [mdpi.com]

• Failure to Thrive

  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]

  DOLK-CDG – Symptoms may include seizures, low muscle tone or floppiness (hypotonia), abnormally small head (microcephaly), scaly skin and failure to thrive. [chop.edu]

  Constitutionally, patients commonly have failure to thrive due to feeding and GI abnormalities and global developmental delay. [atm.amegroups.com]

  Signs and symptoms[edit] Failure to thrive (FTT) - Failure to gain weight and grow at the expected rate.[2] Cerebellar hypoplasia - Small cerebellum, which is the part of the brain that coordinates movement.[3][4][5][6][7] Liver disease - Elevated liver [en.wikipedia.org]

  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]

• Vomiting

  Many children with a CDG develop persistent vomiting and dysfunction of oral motor skills, which involve the muscles of the face and throat. [rarediseases.org]

  Visceral signs (vomiting, diarrhoea, liver failure) were present in 8/20 patients and were always associated with truncal hypotonia and strabismus during the first year. [ojrd.biomedcentral.com]

  Recurrent symptoms in patients with CDG include failure to thrive, global developmental delay, vomiting, stroke-like episodes, and skeletal abnormalities. [atm.amegroups.com]

  Soon in infancy, cyclic episodes of vomiting and/or diarrhea with threatening dehydration were frequent and often urgent reasons for hospitalization. [nature.com]

  The diagnosis is definite with at least two category A criteria (headaches with vomiting, seizures, hemiplegia, cortical blindness and acute focal lesions in neuroimaging) and two category B criteria (high plasma or cerebrospinal fluid (CSF) lactate, [mdpi.com]

• Hepatomegaly

  […] 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]

• Strabismus

  Ophthalmological involvement 25/28 patients had strabismus at some point during their lifetime and which persisted to adulthood for 24 patients. At least four patients underwent one or two strabismus surgeries, with poor outcome. [ojrd.biomedcentral.com]

  Patients do not respond well to reflex tests.[10] Strabismus - Crossed eyes, mainly presented as infantile Esotropia[11] Nystagmus - Involuntary eye movements caused by Cerebellar ataxia.[11][12] Hypotonia - Weak muscle tone, commonly known as floppy [en.wikipedia.org]

  Figure 1 Ichthyosis, hypotonia, and strabismus in a patient with SRD5A3-CDG. Courtesy of NIH, Lynne Wolfe, CRNP, Donna Krasnewich, MD, PhD. [atm.amegroups.com]

  Additional common symptoms include abnormal fat distribution, defects in blood clotting that can cause abnormal bleeding or clotting (coagulation defects), gastrointestinal symptoms such as vomiting and diarrhea, eye abnormalities such as crossed eyes (strabismus [rarediseases.org]

  Morava E et al. in 2012 described refractory epilepsy in 10/14 patients with onset within the first year of life, and recognizable phenotype: microcephaly, developmental delay, strabismus, abnormal blood coagulation tests [36]. [mdpi.com]

• Esotropia

  Patients do not respond well to reflex tests.[10] Strabismus - Crossed eyes, mainly presented as infantile Esotropia[11] Nystagmus - Involuntary eye movements caused by Cerebellar ataxia.[11][12] Hypotonia - Weak muscle tone, commonly known as floppy [en.wikipedia.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]

• Global Developmental Delay

  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]

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]

• Pericardial Effusion

  effusion - Fluid around the heart.[9] Peripheral neuropathy (PN) - Impaired nerve impulse transmission to the legs. [en.wikipedia.org]

  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 [atm.amegroups.com]

  Life-threatening episodes of severe disease with vital organ failure requiring urgent hospitalization include cardiac failure with pericardial effusion and/or hepatic insufficiency with coagulopathy. [nature.com]

For over 40 years, our department has specialized in the diagnosis and treatment of inherited metabolic diseases. [heidelberg-university-hospital.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 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]

We suggest routine screening and follow-up for ophthalmological anomalies in all children diagnosed with CDG syndrome to provide early treatment and adequate counselling. [pubmed.ncbi.nlm.nih.gov]

More than 115 mutations in PMM2 gene have been found to cause this disease.[13] Treatment[edit] There is no cure for PMM2 deficiency. [en.wikipedia.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]

Prognosis depends on the underlying etiology, which is diverse and includes infections, perinatal events and genetic disorders. [mdpi.com]

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 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]

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]

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]

Early diagnosis allows us to initiate specific treatment as soon as possible after birth and thus prevent disability and deaths. [heidelberg-university-hospital.com]

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]

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]