Inborn errors of metabolism

Transcription

1 ESPEN Congress Nice 2010 From child to adult nutrition Inborn errors of metabolism Pascal Crenn

2 Inborn errors of metabolism: from child to adult Pascal Crenn Hôpital Raymond Poincaré Garches. France

3 Inborn errors of metabolism (IEM) = Hereditary metabolic disorders Rare Genetic enzymatic deficiencies (synthesis or breakdown pathway)

4 What are problems and specificities for adult doctors? Continuation of paediatric treatment Primary IEM diagnosis in adults

5 IEM in France (incidence for 2 yrs) Children Adults Total Intoxication Energetic deficiencies Complexes mol Other Total Adapted from Saudubray

6 Specific nutrition in IEM? Intoxication: avoid catabolism Acute: UCD, leucinosis, homocystinuria Chronic : PKU Energetic deficiencies beta oxydation and peroxysome: avoid lipolysis ie fasting (CHO 70%) glucose transportation: ketogenic diet (fat 70%) others

7 IEM in adult: acute clinical/biological presentation 1. Acute encephalopathy -coma 2. Acute psychiatric symptoms 3 Acute neurological sign: stroke, ataxia, PN.. 4. Sudden death -life threatening event 5. Rhabdomyolisis 6. Abdominal pain 7. Acute cardiac failure 8. Bone crisis 9. Hepatic failure 10. Metabolic acidosis 11. Ketosis 12. Hypoglycemia 13. Hyperlactacidemia 14. Hyperammonemia

8 Progress in global care after paediatric follow up Specific diet Drugs, enzymes Care of social and psychological problems Pregnancy (PKU+++) Improvement (survival, quality of life of child affected)

9 Limits with specific diet in IEM Restrictive (psychological problems): withdrawal with acute decompensation for some Possibilities to various deficiencies (AA, EFA, vitamins ): specific/mixture solutions (ex PKU) Specialized and trained dietetician mandatory Avoid fasting for some IEM (b oxydation) Avoid catabolism for others (UCD)

10 Hepatic glycogen storage disease (GSD) in adults

11 Hepatic glycogen storage disease type enzyme frequencies 0 Glycogen Synthase? I Glucose-6-Phosphatase 27 % III Debranching enzyme 28 % IV Branching enzyme 2 % VI Phosphorylase 7 % II V a glycosidase lysosomal (Pompe) Muscle phosphorylase (Mac Ardle)

12 GSD1 Glycogen = hepatomegaly Glycogen G-6-Phosphatase Liver, kidney Glucose-1-P Uric acid Triglycerids Glucose-6-P I Glucose fl Resp. ch Kr Pyruvate LIVER BLOOD Lactate

13 GSD1 in child Clinic : Liver enlargement (+ adenomas), truncal and head obesity Hypoglycaemia with fasting Kidney disease (tubulopathy). Biology : Post absorptive : hypoglycaemia + hyperlactacidemia HyperTG, hyperuricemia Others : Transa, rachitism

14 GSD1 in adults Same clinic, various severity, trend to ameliorate metabolic equilibrium (fast hypoglycaemia) Specific complications : Renal failure Osteopenia Hepatocellular carcinoma* *Franco et al, JIMD 2005

15 Treatment GSD with hypoglycemia Frequent meals (2 to 4 h) with slowly resorbed carbohydrates: maldodextrin, starch, Maïzena (uncooked corn-starch) In some case enteral nutrition during night

16 Phenylketonuria in adults

17 Continuation of PKU paediatric management (neonatal screening) 2 major concerns: 1) Phe-restricted diet continuation? 2) Pregnancy in PKU women

18 Phe-restricted diet continuation? Diet withdrawal in 50 to 90% PKU adults In most patients with a restricted diet continuation Phe > recommendations (variable depending country) in adults (> 16 yrs) < 600 µmol/l (USA) (10 mg/dl) < 700 (UK) < 1200 (Germany) < 1300 (France) *Hanley WB, Am J Med 2004

19 Phe-restricted diet continuation? Arguments Neurological abnormalities Psychological disorders and social misadaptation Pregnancy preparation But no clear demonstration of clinical interest Difficulties to restricted diet Mitchell & Scriver, 2000 Walter et al., Lancet 2002

20 Pregnancy in PKU women Fetopathy (20-30%) in pregnant PKU mothers (if Phe>360 mmol/l): microcephalia, fetal growth, cardiac malformations; abortion Metabolic control (Phe µmol/l) before and during all pregnancy Specific nutritional need, compensate deficiencies Women information+++

21 Factors influencing outcomes in the offspring of mothers with PKU during pregnancy: the importance of variation in maternal blood Phe Methods: 67 mothers PKU/105 children at ages 1, 4, 8, and 14, and the times of starting a Phe-restricted diet, either before or after conception.. Results: -women with PKU should start a Phe-restricted diet before conception for development quotient and congenital heart disease -Phe levels should be consistent throughout the pregnancy to avoid any later developmental complications (IQ). Maillot et al, Am J Clin Nutr 2009

22 Urea cycle disorders (UCD) Orotic acid NH 4 + Acetyl-CoA + MITOCHONDRIA Carbamylphosphate Ornithine CYTOSOL UREA Glutamate N-Acetyl-Glutamate OTC Citrulline Arginine Biochemical diagnosis AA chromato P and U Orotic acid U Argininosuccinate

23 Mitochondrial disorders MNGIE («polip syndrom») Young adult Thymidine phosphorylase defect Intestinal pseudo-obstruction (CIPO) and cachexia PN in severe cases Various defects* with malnutrition and/or myointestinal involvement *Amiot et al, Gastroenterology 2009

24 Abeta and hypobetalipoproteinemia Hypocholesterolemia and lipid malabsorption Spinocerebellar degeneration and ataxia Genetic test Treatment by fat soluble vitamins (E++: 2 to 4 g/d)

25 Diet in various neuro-iem in adults Crenn, Maillot. Rev Neurol 2007

26 Conclusions Heterogeneity of nutrition management: various diet; enteral nutrition or parenteral nutrition for some Specific (vitamins ) complementation Network with paediatricians and dieteticians For a lot of IEM no nutritional specific or dietetic treatment (with exception of deglutition abnormalities: PEG )

27 Crenn, Maillot. Rev Neurol 2007