Expanding the spectrum of PMM2-CDG phenotype

Abstract

Congenital Disorders of Glycosylation (CDG) are a group of recently described inborn errors of metabolism affecting glycosylation. CDG are disorders that have been reported with a great variability in the clinical presentation, especially for the most common PMM2-CDG. The classical form is neurologic but severe forms with multisystem disorders and hydrops fetalis have been described. Here, we extend on the opposite end the clinical spectrum to an asymptomatic PMM2-CDG case. The case was the father of a child who died of neonatal galactosemia few days after birth. He presented without any clinical or biological signs, except a typical CDG 1 pattern in Western blot of glycoproteins associated with a deficient phosphomannomutase activity in blood leukocytes and compound heterozygosity in PMM2 gene. The sister of the father, who was also affected by PMM deficiency, presented with infertility and premature ovarian failure. Finally, the absence of any abnormal clinical or biological signs as for the case completes the clinical spectrum of PMM2-CDG at its extreme end, at the opposite of the supposed total lethality of the R141H homozygous status.