REVISION UCD GUIDELINE – AWMF-Leitlinien-Registernummer 027/006 ABBREVIATIONS ............................................................................................................................................................. 3 INTRODUCTION............................................................................................................................................................... 4 AIM OF THIS GUIDELINE ............................................................................................................................................. 4 PART I: GENERAL RECOMMENDATIONS ............................................................................................................... 5 1 CLINICAL DIAGNOSIS – SIGNS AND SYMPTOMS .......................................................................................... 5 1.1 CLINICAL SUSPICION OF UCD ................................................................................................................................. 5 1.2 ACUTE AND CHRONIC PRESENTATIONS ................................................................................................................... 5 1.3 TRIGGERS OF METABOLIC CRISIS ............................................................................................................................ 7 1.4 LABORATORY INVESTIGATIONS .............................................................................................................................. 7 2 DIFFERENTIAL DIAGNOSIS ................................................................................................................................. 8 2.1 CONDITIONS AND GENETIC DISORDERS OTHER THAN UCDS PRESENTING WITH NEONATAL HYPERAMMONEMIA .... 8 2.2 CONDITIONS AND GENETIC DISORDERS WHICH CAN PRESENT WITH LATE-ONSET HYPERAMMONEMIA .................... 9 3 BIOCHEMICAL AND ENZYMATIC ANALYSIS ................................................................................................ 9 3.1 ALGORITHM FOR FURTHER INVESTIGATIONS OF HYPERAMMONEMIA ...................................................................... 9 3.2 ENZYME ANALYSIS ................................................................................................................................................10 3.3 ROLE OF LIVER BIOPSY OR OF OTHER TISSUE SAMPLES DURING WORK-UP FOR A SUSPECTED UCD .....................10 4 GENETIC ANALYSIS ............................................................................................................................................. 10 4.1 ROLE OF MOLECULAR GENETIC ANALYSIS FOR DIAGNOSIS OF UCDS.....................................................................10 4.2 PROGNOSTIC VALUE OF MUTATION ANALYSIS .......................................................................................................11 4.3 ROLE OF STRUCTURE ANALYSIS AND ASSESSMENT OF PATHOGENICITY OF MUTATIONS ........................................11 5 PRENATAL TESTING ............................................................................................................................................ 11 5.1 ROLE OF PRENATAL TESTING IN UCDS ..................................................................................................................11 5.2 METHODS AND SAMPLES FOR PRENATAL TESTING IN UCDS ..................................................................................11 6 NEWBORN SCREENING ....................................................................................................................................... 12 6.1 NEWBORN SCREENING FOR MITOCHONDRIAL UCDS..............................................................................................12 6.2 NEWBORN SCREENING FOR CYTOSOLIC UCDS ......................................................................................................12 7 MANAGEMENT OF ACUTE HYPERAMMONEMIA ....................................................................................... 13 7.1 INITIAL MANAGEMENT OF ACUTE HYPERAMMONEMIA ...........................................................................................13 7.2 DRUGS AND DOSAGES TO BE USED IN ACUTE DECOMPENSATIONS OF UCDS ..........................................................15 7.3 MANAGEMENT OF A NEONATE AT RISK OF A UCD AT BIRTH .................................................................................17 7.4 CRITERIA TO START EXTRACORPOREAL DETOXIFICATION......................................................................................17 7.5 MANAGEMENT OF ACUTE HYPERAMMONEMIA IN ADULTS .....................................................................................17 7.6 METHODS TO BE USED FOR EXTRACORPOREAL DETOXIFICATION ...........................................................................17 7.7 DIETARY MANAGEMENT DURING ACUTE DECOMPENSATION ..................................................................................18 8 LONGTERM MANAGEMENT OF UCDS ........................................................................................................... 19 8.1 PRINCIPLES OF DIET FOR LONG-TERM TREATMENT OF UCDS .................................................................................19 8.2 PRACTICAL ASPECTS OF DIET FOR LONG-TERM TREATMENT OF UCDS ..................................................................21 8.3 PHARMACOTHERAPY IN LONG-TERM TREATMENT OF UCDS .................................................................................23 8.4 SPECIAL SITUATIONS: VACCINATIONS AND SURGERY & ANESTHESIA ....................................................................25 9 LIVER TRANSPLANTATION FOR UCD PATIENTS ....................................................................................... 26 9.1 LONGTERM NEUROLOGICAL OUTCOME AFTER LIVER TRANSPLANTATION ..............................................................26 9.2 QUALITY OF LIFE AFTER LIVER TRANSPLANTATION ...............................................................................................26 9.3 INDICATIONS AND IDEAL AGE FOR LIVER TRANSPLANTATION ................................................................................26 9.4 RECOMMENDED TYPES OF DONOR AND TRANSPLANT ............................................................................................27 2 9.5 ETHICAL CONSIDERATIONS RELATED TO LIVER TRANSPLANTATION ......................................................................27 10 MONITORING ......................................................................................................................................................... 27 10.1 MONITORING IN PLASMA .......................................................................................................................................27 10.2 MONITORING IN URINE ..........................................................................................................................................28 10.3 ROLE OF NEUROIMAGING .......................................................................................................................................28 10.4 PSYCHOLOGICAL ASPECTS IN THE CLINICAL CARE FOR UCD PATIENTS .................................................................29 PART II: DETAILED RECOMMENDATIONS ........................................................................................................... 30 11 NAGS AND CPS1 DEFICIENCY ........................................................................................................................... 30 11.1 THE ROLE OF ENZYME ANALYSIS FOR DIAGNOSIS OF NAGS OR CPS1 DEFICIENCY ...............................................30 11.2 GENETIC ANALYSIS OF NAGS AND CPS1 DEFICIENCY ..........................................................................................31 11.3 TREATMENT OF NAGS DEFICIENCY – SPECIAL CONSIDERATIONS ..........................................................................31 11.4 TREATMENT OF CPS1 DEFICIENCY – SPECIAL CONSIDERATIONS ...........................................................................31 12 OTC DEFICIENCY .................................................................................................................................................. 31 12.1 ENZYME ANALYSIS FOR DIAGNOSIS OF OTC DEFICIENCY ......................................................................................31 12.2 GENETIC ANALYSIS OF OTC DEFICIENCY ..............................................................................................................31 12.3 INVESTIGATIONS TO DIAGNOSE SUSPECTED FEMALE OTC CARRIERS.....................................................................32 12.4 TREATMENT OF OTC DEFICIENCY – SPECIAL CONSIDERATIONS .............................................................................32 13 ASS DEFICIENCY (CITRULLINEMIA TYPE 1) ............................................................................................... 32 13.1 ENZYME ANALYSIS OF ASS DEFICIENCY ...............................................................................................................32 13.2 GENETIC ANALYSIS OF ASS DEFICIENCY ...............................................................................................................32 13.3 TREATMENT OF ASS DEFICIENCY – SPECIAL CONSIDERATIONS .............................................................................33 14 ASL DEFICIENCY .................................................................................................................................................. 33 14.1 ENZYME ANALYSIS OF ASL