| Topic | Key facts | Ontology / IDs | Key sources |
|---|---|---|---|
| Identity / overview | MPI-congenital disorder of glycosylation (MPI-CDG) is a rare disorder of protein N-glycosylation caused by pathogenic variants in **MPI**; unlike many other CDGs, it is dominated by gastrointestinal, hepatic, endocrine, and coagulation manifestations, with usually no intellectual disability or major neurologic impairment. Former names include **CDG-Ib**, **CDG type Ib**, **carbohydrate-deficient glycoprotein syndrome type Ib**, **phosphomannose isomerase deficiency / mannose phosphate isomerase deficiency**, **protein-losing enteropathy-hepatic fibrosis syndrome**, and **Saguenay-Lac Saint-Jean syndrome**. | **OMIM:** 602579; MeSH in trial browse: “Congenital disorder of glycosylation type 1B”; suggested disease label: MPI-CDG | (pqac-00000010, pqac-00000017) |
| Inheritance / gene | **Autosomal recessive** disorder due to biallelic pathogenic variants in **MPI** on chromosome 15q. The MPI gene has **8 exons** and spans ~**5 kb**. | Suggested gene: **MPI**; inheritance: AR | (pqac-00000010, pqac-00000022) |
| Core mechanism | MPI catalyzes **fructose-6-phosphate ↔ mannose-6-phosphate**, the first step toward GDP-mannose synthesis for N-glycosylation. MPI deficiency lowers intracellular mannose availability; in patients, endogenous mannose is insufficient, leading to **protein N-hypoglycosylation**. Consensus guideline notes plasma mannose is **<10 μmol/L** in MPI-CDG vs **50–100 μmol/L** in healthy individuals; glycosylation can be normalized when serum mannose exceeds **~200 μmol/L**. Excess mannose can cause **Man-6-P accumulation**, glycolytic inhibition, ATP depletion, and neurologic toxicity (“honeybee effect”). | Suggested GO terms: **protein N-linked glycosylation**, **mannose metabolic process**; suggested CHEBI concept: **D-mannose** | (pqac-00000008) |
| Typical onset / course | Symptoms begin in **infancy** in the large majority; consensus review found **93%** infantile onset with mean onset **1.2 years**, but adolescent presentations and asymptomatic adults have been reported. In the 2023 review, onset ranged **birth to 15 years**, with **43/50** cases starting before age 2. Diagnostic delay ranged **0–30 years** (median **2.15 years**). | Suggested onset terms: congenital/infantile; chronic multisystem course | (pqac-00000009, pqac-00000002) |
| Hallmark phenotypes (2023 frequencies) | 2023 literature review of 52 patients reported: **chronic diarrhea 41/46**, **vomiting 23/27**, **hepatomegaly 39/44**, **hepatic fibrosis 20/37**, **protein-losing enteropathy 30/36**, **elevated transaminases 24/34**, **hyperinsulinemic hypoglycemia 24/34**, **hypoalbuminemia 33/38**, **prolonged coagulation 26/30**, **splenomegaly 13/21**, **non-pitting edema 14/20**, **failure to thrive 13/36**, **portal hypertension 4/9**, **epilepsy 2/17**, **thrombosis 12/14**, **elevated leukocytes 5**; **intellectual disability 0/28**. | Reliable phenotype suggestions: **hepatomegaly**, **diarrhea**, **vomiting**, **protein-losing enteropathy**, **hypoglycemia**, **hypoalbuminemia**, **hepatic fibrosis**, **portal hypertension**, **thrombosis** | (pqac-00000002, pqac-00000001) |
| Diagnostics | First-line biochemical screen: **serum/plasma transferrin isoelectric focusing (TIEF)** showing **CDG type I pattern** (decreased tetrasialotransferrin, increased disialo-/asialotransferrin); reported **100% sensitivity** in described genotyped patients, but non-specific vs other CDG-I disorders. **HPLC/capillary electrophoresis** for CDT% also reported **100% sensitivity** in described patients. Confirmation: **MPI enzyme assay** in fibroblasts/leukocytes or **MPI gene testing**; enzyme activity usually **<10%** of normal, though **14–21%** residual activity has been reported in some severe cases. Differential diagnosis includes **PMM2-CDG**, **galactosemia**, **hereditary fructose intolerance**, liver disease, chronic alcohol abuse, and other causes of hypoglycemia/PLE/hepatopathy. | Suggested lab/ontology terms: transferrin IEF, carbohydrate-deficient transferrin; gene: **MPI** | (pqac-00000016, pqac-00000022, pqac-00000011, pqac-00000014) |
| First-line treatment / dose | Standard disease-specific treatment is **oral D-mannose**. Consensus recommended dose: **150–170 mg/kg/dose, 4–5 times daily**. In the 2023 review, **26/30** treated patients improved clinically/laboratorily; symptoms in the index case resolved within **1 week**. Monitoring every 3 months during oral therapy includes **unconjugated bilirubin, blood count, HbA1C, and mannose levels**; target mannose levels suggested as **T0 >20 μmol/L** and **T1h >100 μmol/L**. | Suggested treatment term: **D-mannose**; NCIT suggestion only where available concept exists for mannose | (pqac-00000020, pqac-00000003, pqac-00000000) |
| Key limitation / persistent liver disease | Mannose improves many clinical and biochemical abnormalities but **does not reliably halt liver disease**. Consensus guideline states patients may still develop **progressive liver fibrosis**, likely because characteristic lesions reflect **ductal plate malformation / congenital hepatic fibrosis**, which do not respond to mannose. Selected severe cases may require **liver transplantation**, especially for **portal hypertension with hepatopulmonary syndrome**. | Suggested anatomy: **liver**; suggested pathology: **hepatic fibrosis**, **portal hypertension** | (pqac-00000013, pqac-00000007) |
| Prognosis / mortality | Consensus review of 35 patients found **mortality 23.5% (8/35)**; all deaths occurred in infancy/early childhood at **4 months to 5 years** (median **2.2 years**). Causes, when known, included **hepatic failure (n=2)** and **sepsis (n=1)**; many deaths occurred before diagnosis/treatment. In the 2023 review, **8/11 untreated** patients died, supporting major benefit from timely diagnosis and mannose therapy. | Suggested outcome terms: mortality, hepatic failure, sepsis | (pqac-00000009, pqac-00000000) |
| Clinical trial / implementation | **NCT03404869**: “**Study of ORL-1M (D-mannose) in Patients With CDG-Ib**,” sponsor **Orpha Labs**; **Phase 1/2**, single-group, open-label, estimated **n=5**; primary outcome: improvement in **hypoglycemia, diarrhea and vomiting** at **6 months**; secondary outcome: improved **serum transferrin glycosylation** at **30 days**. Registry overall status is currently listed **UNKNOWN**; last known status **RECRUITING**; first posted **2018-01-19**. | **NCT03404869** | (pqac-00000017) |
| Animal / experimental models | **Zebrafish mpi morphants**: **13% residual Mpi activity** at 4 dpf, **50% embryonic lethality** by 4 dpf, and multisystem abnormalities in **82%** of survivors (small eyes, dysmorphic jaws, pericardial edema, small liver, curled tails); phenotypes were rescued by mannose **only if given before 24 hpf**. **Mouse models**: complete **Mpi knockout** is embryonic lethal; **hypomorphic mice** with patient-like residual activity appeared largely normal but had ~**15% embryonic lethality**. Mannose exposure worsened outcomes, reducing litter size and survival to weaning by **40%** and **66%**, respectively, and ~**50%** of survivors developed ocular defects/blindness, highlighting species-specific toxicity and caution in pregnancy. | Suggested model systems: **Danio rerio**, **Mus musculus** | (pqac-00000024, pqac-00000018, pqac-00000005) |


*Table: This table condenses the most actionable disease-characterization points for MPI-CDG, including identity, mechanism, phenotype frequencies, diagnosis, treatment, prognosis, trial activity, and model systems. It is formatted for direct use in a disease knowledge-base entry and cites the supporting evidence contexts.*