Table 2.
Main causes of hypoglycaemia related to inborn errors of metabolism (IEM) in adults
| Diseases | Persistent hypoglycaemia | Hypoglycaemia as an indicator | Positive and molecular diagnosis |
|---|---|---|---|
|
Fasting hypoglycaemia | |||
|
Glycogenolysis disorders |
|
|
I: high blood lactates especially before meals, hypertriglyceridaemia, hyperuricaemia |
|
Glycogen Storage Disease |
|
|
Ketones rather low |
| Liver: |
|
|
|
| I, VI, IX, 0, Fanconi-Bickel |
|
|
III: high blood lactates especially after meals, hypertriglyceridaemia, |
| |
I, III, 0, Fanconi-Bickel |
|
Ketones rather high |
| Mixed: |
|
|
|
| III, IV |
|
III (debranching enzyme or amylo-1,6-glucosidase enzyme) |
GSD I/III: DNA (leucocytes) |
|
Defect of fatty acid oxidation |
|
|
- no ketones (or rather low during hypoglycaemia) |
| - carnitine cycle (CPT1/2) |
- CPT1 |
|
- high free carnitine plasma level (CPT1) |
| - ß fatty acid oxidation |
- VLCAD, MCAD, SCHAD, LCHAD |
|
- accumulation of plasma acylcarnitines (example : High C8 and high C8/C2 ratio in MCAD) |
| - electron transfer |
|
|
|
| - ketogenesis |
- HMG-CoA lyase |
MCAD |
- urine organic acid accumulation - ß oxidation in vitro (lymphocytes) |
| |
|
|
- DNA (leucocytes) |
|
Gluconeogenesis |
Fructose-1,6-biphosphatase |
Fructose-1,6-biphosphatase |
- lactic acidosis |
| |
|
|
- high alanine |
| |
|
|
- ketosis |
| |
|
|
- high glycerol |
| |
|
|
- urine: high 3 Ph glycerol |
|
Postprandial hypoglycaemia | |||
| NIPHS (sometimes in fasting period) |
- hypoglycaemia during infancy (SUR.1, Kir6.2, SCHAD, GDH, Glucokinase |
- Glucokinase mutation |
- hyperinsulinism |
| |
- sometimes progression to diabetes in adulthood (especially SUR-1) |
|
- hyperammonemia (GDH) - Genotyping (DNA leucocytes) |
| CDG Ia, Ib, Id (sometimes at anytime) |
- CDG Id |
no |
Isoelectric focussing of transferrin |
| |
|
|
- phosphomannomutase gene (Ia) |
| |
|
|
- phosphomannomutase isomerase gene (Ib) |
| |
|
|
- 1,3-mannosyltransferase (Id) |
| |
|
|
Hyperinsulinism |
| Inherited fructose intolerance |
- After ingestion of fructose (fruits, sucrose, sweet foods) |
|
- fructose test tolerance iv |
| |
- Late postprandial period |
|
- breath test fructose |
| |
|
|
- DNA leucocytes : aldolase B gene |
|
Exercise-induced hypoglycaemia | |||
| NIPHS | - MCT1 | yes | Genotyping (DNA leucocytes) |
GSD, glycogen storage disease; CPT, carnitine palmitoyltransferase-1; VLCAD, very long-chain acyl-CoA dehydrogenase; MCAD, medium-chain acyl-CoA dehydrogenase; LCHAD, long-chain 3-hydroxyacyl-CoA dehydrogenase; SCHAD, short-chain L-3-hydroxyacyl-CoA dehydrogenase;
lGDH, glutamate dehydrogenase; MCT1, monocarboxylate transporter 1; CDG, congenital disorders of glycosylation; NIPHS, non-insulinoma pancreatogenic hypoglycaemia syndrome.