CDGIL is a multisystem disorder caused by a specific defect in glycoprotein biosynthesis. It is characterized by severe microcephaly, hepatomegaly, and bronchial asthma. Other features include defects in the nervous system, such as development delay and psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, seizures, and immunodeficiency. Brain MRIs of affected patients may reveal volume loss in the cerebral hemispheres and cerebellum and delayed myelination. Some patients may also present with bipolar affective disorder.
CDGIL patients require life-long treatment and support. The treatment is focused on symptoms and may include physical therapy, and educational aids. Anti-epileptic medications are administered in the case of seizures. Researchers are studying gene therapy as an approach to therapy for individuals with CDGs or related disorders. 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 in question. However, gene therapy is still in a nascent stage and treatment options using gene therapy are not popularly available.
AlSubhi et al. (2016) studied four patients from a large consanguineous family diagnosed with ALG9-CDG. The index case was a 6-year-old female who was born with hip dislocation, dysmorphic features (frontal bossing, depressed nasal bridge, low seated ears, large mouth, and hypertelorism), and congenital heart disease in the form of minor tricuspid regurgitation. When she reached the age of 4-months, the patient started to develop frequent seizure attacks in the form of frequent clusters of clonic and tonic movements with up-rolling of the eyes. After the first 5 years of life, the patient became seizure free with a normal EEG but she showed global developmental disability. All growth parameters were at the 5th percentile at 6-years. She was hypotonic and showed exaggerated deep tendon reflexes but without clonus. Skeletal survey showed delayed bone age and mild skeletal dysplasia. Brain MRI showed global cerebrum and cerebellar atrophy with delayed myelination. Her family history revealed three other affected cousins. Two of them had a similar presentation to the index, with the only difference being that one of the two had less severe developmental disability. The fourth patient was a 25-day-old boy diagnosed by fetal ultrasonography at 28 weeks of gestation with hydrops fetalis, which consisted of severe skin edema, pericardial effusion, and ascites. At birth, he was found to have atrial septal defect and mild dilatation of the right ventricle. Skeletal survey showed mild skeletal dysplasia. Cranial ultrasound showed wide subarachnoid spaces. The clinical and the biochemical findings described in these patients added to the spectrum of presentations of ALG9-CDG, with skeletal dysplasia, ranging in severity from mild to severe, appearing to be a consistent feature of the condition.