Background: Phosphoglucomutase 1 (PGM-1) deficiency (glycogen storage disease type XIV) is a congenital disorder of glycosylation with impaired glycogen and glycan biosynthesis causing hypoglycemic episodes. Other clinical features include brachial arch manifestations, myopathy, endocrinopathies, and elevated liver function tests.
Objectives: Elucidating the substantial genetic, diagnostic and therapeutic challenges in a patient presenting with Pierre Robin sequence and severe hypoglycemic episodes.
Methods and Results: A 1.25 years old child with Pierre Robin sequence presented with frequent, fasting and postprandial hypoglycemic episodes, augmented following a nutritional switch to lactose free formula.
In spite of almost continuous feeding via PEG- glucose monitoring revealed frequent hypoglycemic episodes with relatively low glucose variations and a paradoxical decline in glucose levels from 57 mg/dl to 44 mg/dl during glucagon test.
Repeated "critical samples" did not elucidate a pathophysiologic etiology for the hypoglycemia.
Transferrin isoelectric focusing showed decreased tetrasialo-transferrins and increased asialo-, monosialo-, disialo and trisialotrasferrins indicating interrupted synthesis and processing of glycans - a highly specific pattern of PGM1 deficiency.
PGM-1 sequencing revealed compound heterozygotes mutations- p.F380fs21* (exon 7) and p.E450*(exon 9)- with early stop codons and premature protein truncation.
A trial of galactose supplementation recently reported to allow efficient glycogenesis and glycan synthesis resulted in profound clinical and biochemical improvement enabled significant pauses of 90 minutes between meals without hypoglycemia.
Conclusion: In this unique case of recurrent hypoglycemic episodes the identification of the rare glycosylation defect -PGM-1 deficiency- enabled dramatic clinical improvement achieved by a relatively simple nutritional modification.
