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.