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Mol Genet Metab. 2001 May;73(1):77-85.

Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type Ib: long-term outcome and effects of mannose supplementation.

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1
The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.

Abstract

We report the diagnosis and follow-up of two sibs reported in 1980 with recurrent venous thromboses and protein-losing enteropathy; one sib with biopsy-proven hepatic fibrosis died at age 5. The combination of symptoms was suggestive of the recently characterized congenital disorder of glycosylation type Ib (CDG-Ib), which is caused by a deficiency of the enzyme phosphomannose isomerase (PMI). An abnormal serum transferrin isoelectric focusing (IEF) pattern and a reduced PMI activity confirmed the diagnosis of CDG-Ib. Furthermore, mutational analysis of the MPI gene revealed two missense mutations, 419 T --> C (I140T) and 636 G --> A (R219Q), a single base substitution in intron 5, 670 + 9G --> A, as well as a polymorphism 1131A --> C (V377V) in both sibs. The surviving 33-year-old sib has had no further symptoms following childhood. Short-term low-dose oral mannose supplementation improved her transferrin IEF pattern and normalized her antithrombin III activity, further substantiating the beneficial effect of mannose in CDG-Ib. When her mannose blood level was measured, she showed a lower steady-state level but a faster mannose clearance rate. These results suggest that the clinical manifestations of PMI deficiency, although serious in childhood, can improve with age, even without mannose therapy, and allow for a normal adult life. However, the long-term prognosis may vary from patient to patient.

PMID:
11350186
DOI:
10.1006/mgme.2001.3161
[Indexed for MEDLINE]

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