Congenital disorder of glycosylation type 1T with a novel truncated homozygous mutation in PGM1 gene and literature review.

ABSTRACT

The congenital disorders of glycosylation are a group of clinically and biochemically heterogeneous diseases characterized by multisystem involvement due to glycosylation defect of protein and lipid. Here we report a 49-year-old man with exercise-induced fatigue and pain of muscle, tachypnea, cleft palate and bifid uvula. Exercise induced elevation of serum creatine kinase (CK), ammonia and lactic acid was recorded. The abnormal levels of myoglobin, CK-MB and LDH as well as S-T elevation in electrocardiogram were observed in repeated hospitalization recordings. Electromyography showed myopathic damage. Repetitive nerve stimulation test of low rates showed decrement in the left deltoid muscle. He was identified with a novel homozygous frameshift variant in Phosphoglucomutase type 1 gene (c.405delT p.N135Kfs*9) by whole exome sequencing. Muscle biopsy exhibited minimal variation in fiber size without abnormal glycogen accumulation. Compared with controls', the patient's sample showed no signal at ∼61 kDa using N- or C-terminus antibody of Phosphoglucomutase type 1 in western blotting. A signal at ∼20 kDa was detected in patient using N-terminus antibody. Immunofluorescence revealed trace expression of C-terminus and a much lower expression of N-terminus on the sarcolemma than normal. Our findings indicate that c.405delT encodes a truncated protein with abnormal distribution and expression in skeletal muscle. In conclusion, genes associated with congenital disorders of glycosylation should be analyzed in patients with maxillofacial dysplasia, exertional weakness, cardiac involvement and exercise-induced-ammoniemia, without glycogen storage in skeletal muscle.