Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.4.2.8 (phosphomannomutase)
 238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbohydrate deficient glycoprotein syndromes (CDGS) are inherited disorders in glycosylation. Isoelectric focusing of serum transferrin is used as a biochemical indicator of CDGS; however, this technique cannot diagnose the molecular defect. Even though phosphomannomutase (PMM) deficiency accounts for the great majority of known CDGS cases (CDGS type Ia), newly discovered cases have significantly different clinical presentations than the PMM-deficient patients. These differences arise from other defects affecting the biosynthesis of N-linked oligosaccharides in the endoplasmic reticulum and in the Golgi compartment. The most notable is the loss of phosphomannose isomerase (PMI) (CDGS type Ib). It causes severe hypoglycemia, protein-losing enteropathy, vomiting, diarrhea, and congenital hepatic fibrosis. In contrast to PMM-deficiency, there is no developmental delay nor neuropathy. Most symptoms in the PMI-deficient patients can be successfully treated with dietary mannose supplements. Another defect is the lack of glucosylation of the lipid-linked oligosaccharide precursor. The clinical features of this form of CDGS are milder, but similar to, PMM-deficient patients. Yeast genetic and biochemical techniques were critical in unraveling these disorders since many of the defective genes were known in yeast and corresponding mutants were available for complementation. Yeast strains carrying mutations in the homologous genes are likely to provide conclusive identification of the primary defects in novel CDGS types that affect the synthesis and transfer of precursor oligosaccharides.
 ...
PMID:Molecular basis of carbohydrate-deficient glycoprotein syndromes type I with normal phosphomannomutase activity. 1057 Oct 10

Physicians have become accustomed to thinking of certain inborn errors of metabolism (e.g., lysosomal, peroxisomal, and mitochondrial diseases) as being associated with specific subcellular organelles. In recent years, a family of disorders of N-glycosylation has been recognized, in which the metabolic defect is expressed in the cytosol, endoplasmic reticulum, and Golgi apparatus. These could be conveniently thought of as "prelysosomal" disorders. At least six of these entities are characterized by hypoglycosylation of many glycoconjugates, and have been designated as the carbohydrate-deficient glycoprotein syndromes. Given the ubiquity of the products of N-glycosylation in the cellular economy, it is not surprising that these defects in metabolism have protean clinical manifestations. Delayed development and other neurologic symptoms are wedded to variable dysfunctions of the heart, liver, and endocrine and coagulation systems. Patients can have dysmorphic features or cerebellar hypoplasia, attesting to the antenatal expression of these disorders. The most frequently recognized phenotype (several hundred cases worldwide) has been designated carbohydrate-deficient glycoprotein syndrome type la, and results from mutations in phosphomannomutase, a cytosolic enzyme involved in the synthesis of the lipid-linked oligosaccharide that is eventually attached to nascent glycoproteins through the amide group of asparagine residues. All forms of carbohydrate-deficient glycoprotein syndrome express an excess of hypoglycosylated isoforms of circulating transferrin, which serves as a useful screening tool. Physicians should consider screening for carbohydrate-deficient glycoprotein syndrome in individuals with delayed development, seizures, strokelike episodes, cerebellar hypoplasia, and demyelinating neuropathy with or without other signs of multisystem disease.
 ...
PMID:Screening for "prelysosomal disorders": carbohydrate-deficient glycoprotein syndromes. 1059 62