A rare, inherited condition caused by a dysfunctional enzyme that fails to produce lipid anchors that are essential to carry sugars across the cell. Symptoms manifest during infancy or early childhood, including developmental delay, intellectual disability, seizures and complex movement disorders. In a subset of patients, symptoms worsen during adulthood.
Symptoms
DHDDS-CDG is a very rare condition which mostly affects the brain. There are two types of DHDDS-CDG, caused by different inheritance patterns. The recessive form, inherited by both parents, leads to blindness and has been reported in families Ashkenazi Jewish origin. The dominant form, where the patients have only one faulty copy of the gene, can be inherited through one of the parents or arise during conception (called a De Novo mutation). To date, 59 patients with a dominant form of DHDDS-CDG have been reported in literature, and around 30-40 families with the recessive form have been reported.
Individuals with dominant DHDDS-CDG typically develop their first signs and symptoms of the condition during infancy or early childhood. During childhood and adulthood, they can develop additional new symptoms, or their existing symptoms can worsen. Worsening/progression of symptoms is quite unique for DHDDS-CDG, and usually not observed in other types of CDG. Characteristic symptoms for the dominant form are developmental delay, seizures, regression, and complex movement disorders. The movement disorder is variable and consist of shaking/trembling of hands (tremor), loss of coordination (ataxia), involuntary movements (chorea), muscle jerks (myoclonus) or involuntary muscle contractions (dystonia).
In most patients, no specific laboratory abnormalities or brain imaging abnormalities are found, which can suggest the presence of DHDDS-CDG. For patients with the recessive form of the disease, altered dolichol-18/19 ratios can be found in blood and urine. In blood, hypoglycosylation can be observed for the recessive form. These findings are not present in the dominant form.
Diagnosis
The ultimate diagnosis is made by using genetic testing in blood. Individuals with DHDDS-CDG can have either one or two faulty copies of the DHDDS gene.
Treatment and Prognosis
To date, there are no known specific treatment options for DHDDS-CDG. Treatment is aimed at the management of symptoms and the prevention of complications.