An evaluation of ALG6-CDG (former CDG Ic)
A recognisable phenotype with epilepsy, proximal muscle wakness, ataxia and behavioural and limb anomalies.
By Fiona Waddell
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ALG6-CDG, previously called CDG Ic, is a congenital disorder of glycosylation caused by a defect on the enzyme alpha1,3-glucosyltransferase. After phosphomannomutase 2-CDG (PMM2-CDG), ALG6-CDG is the second most common CDG. Eva Morava, MD, PhD, Tulane University Medical School (New Orleans, USA) and Center for Metabolic Diseases, University Hospital Leuven (Belgium. More information HERE) and her team evaluated the clinical data of 41 patients diagnosed with ALG6-CDG between 1995 and 2013 either registered by the Euroglycan database or followed by a clinician involved in Euroglycanet and participating in the reported study.
The study showed that hypotonia and developmental delay were the most common symptoms, epilepsy was present in the majority of the patients. Besides this, Morava found also a high percentage of other neurological symptoms, including absent speech, ataxia, proximal muscle weakness and visual loss. Several patients had behavioural abnormalities, including sleep disturbance, autistic behaviour, mood swings and periods of inertia alternating with periods of aggressive behaviour, which is unusual for most CDG-I patients.
Special features included facial dysmorphism, cardiomyopathy and limb malformations were also found in several patients. Some patients had severe distal limb reductions and abnormal fat distribution was present in a few patients. Protein Losing Enteropathy (PLE) is one of the most significant life-threatening symptom of ALG6-CDG. Four patients with PLE followed a low-fat/elementary protein diet and two patients received octreotide injections to decrease enteral protein loss. This turned out to be successful. Anaemia was common as well in ALG6-CDG patients. According to the data, most ALG6-CDG patients reached puberty and a few reached adulthood. The oldest patient was a 40-year old Dutch woman, but because chronic intestinal protein loss, frequent infections, hypoglycemia and hypogammaglobulinemia might lead to early mortality in young ALG6-CDG patients, prospective, regular screening of glycemia, coagluation and endocrine and liver function is necessary.
Since some children only present with hypotonia and seizures, or behavioural abnormality and speech disability, Morava and her team recommend systematic glycosylation screening in developmental disability.