Introduction
Diagnosis
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Plasma glucose, insulin, C-peptide
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Creatinine, liver parameters, NF, CRP, CPK, uric acid, triglycerides
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Cortisol, GH, IGF1
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Oral hypoglycaemic agents
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Blood lactate
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Free fatty acids
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3-ßOH butyrate
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Acylcarnitines (dried blood spots)
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Plasma amino acids
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Ammonaemia
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Carnitine status (free and total)
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Urine dipstick (for ketone bodies)
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Urinary organic acids
When to consider a glycogenolysis disorder | When to consider a fatty acid oxidation disorder | When to consider a gluconeogenesis disorder |
---|---|---|
- Fasting hypoglycaemia | - Fasting hypoglycaemia | - Long fasting hypoglycaemia |
- Presence of ketosis (except for GSD I) | - Absence of ketosis | - Presence of ketosis |
- High blood lactate | - High CPK levels | - Lactic acidosis |
- Hyperuricaemia | - Acylcarnitine accumulation (example: MCAD: high C8 and high C8/C2 ratio) | - High alanine level during fasting |
- Hypertriglyceridaemia | - Urine organic acid accumulation (example: HMG-CoA lyase: 3-Hydroxy-3-Methylglutaric acid) | - Blood glycerol and urine glycerol-3-phosphate accumulation during fasting |
- Hepatomegaly | - High free carnitine plasma level (CPT1) | |
- Muscular signs | - Family history of sudden death |
Diseases | Persistent hypoglycaemia | Hypoglycaemia as an indicator | Positive and molecular diagnosis |
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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) |