CDG is being diagnosed more quickly in the UK now that there is increased awareness of it in the medical community. Click here for a full list of CDG subtypes.
There are various ways in which signs and symptoms of CDG first present to parents and clinicians: through pregnancy scans, though problems at birth, through the health visitor’s visit, or through a General Practitioner (GP). The more severe the effects of the CDG, the more quickly signs and symptoms are noticed.
The diagnosis of CDG should be considered in any child with unexplained (and often profound) developmental delay, failure to thrive, stroke-like symptoms, seizures and cerebellar dysfunction. CDG affects most organ systems to varying degrees, so children will often display abnormalities in liver enzymes, digestion and absorption, glandular function (i.e. thyroid), blood clotting, and immunologic function (infectious susceptibility).
Initial concerns will be escalated to a paediatrician (children’s doctor) at a local hospital, who will then take a detailed patient history, and conduct a thorough clinical evaluation. A diagnosis of CDG may then be suspected based on the patient’s characteristics (doctors call this the patient’s ‘presentation’). Some of the signs and symptoms of CDG are listed below.
The family stories on our community page tell of different family journeys to diagnosis.
Signs and symptoms
The symptoms and severity of CDG vary from child to child. Some of the symptoms become more prominent at different ages. Most types of CDG are associated with minor differences in facial and body features, neurological problems, slow growth, clotting problems, liver and/or intestinal problems. Some CDG children have significant medical problems during infancy. Physicians should suspect CDG in children who present with the following signs and symptoms:
- Hypotonia (low muscle tone)
- Failure to thrive (slow growth)
- Developmental delay
- Hepatopathy (liver disease) presenting as elevated liver enzymes (ALT and AST)
- Coagulopathy (any bleeding may be severe or prolonged, may show as abnormal clotting as adults)
- Esotropia (crossed eyes)
- Cerebellar hypoplasia (changes in the brain that can be seen on brain imaging)
At a later age, adolescence or adulthood, affected individuals may have these additional clinical features:
- Ataxia (poor balance and movement coordination)
- Dysarthria (slurred speech)
- Absent puberty in females
- Retinitis pigmentosa (pigment in the retina of the eye)
- Progressive scoliosis (curvature of the spine)
- Joint contractures (deformity as a result of stiffness or constriction in the connective tissues of the body)
It is recommended that in any unexplained syndrome, CDG should be considered.
The first clinical test is to analyse how much glycosylation is present on glycosylated proteins in the body. There is a protein in the blood, called transferrin, and this is normally glycosylated, so a simple blood test is taken and the transferrin analysed. Any abnormal transferrin patterns can be detected by separating the molecules with specialised techniques.
This test is useful to identify any defect in N-linked glycosylation (type I CDG) but is not 100% accurate and further tests may be needed. In the same way, apolipoprotein CIII patterns can be analysed to detect O-linked glycosylation (type II CDG).
Further testing is used to determine the CDG subtype (there are many and counting). This could be done by testing for specific enyme activity, but not all CDGs can be detected in this way.
Molecular genetic testing is used to confirm the diagnosis. Sometimes this is done in Leuven, Belgium, by CDG experts.