The spectrum and outcome of the. neonates with inborn errors of. metabolism at a tertiary care hospital

Transcription

1 The spectrum and outcome of the neonates with inborn errors of metabolism at a tertiary care hospital Dr. Sevim Ünal Neonatology Division, Ankara Children s Hematology Oncology Research Hospital, Ankara, TURKEY

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3 Hereditary affections Commonly present around the time of birth Most affected newborns born healthy, subsequently deteriorate Constitute a significant diagnostic and therapeutic challenge for pediatricians - neonatologyst

4 Easily misdiagnosed as sepsis or birth asphyxia Most patients require aggressive support (MV, dialysis) Large resources require to care of patients even for relatively short NICU / PICU stays Diagnosis often needs to be established quickly, early measurement of biochemical markers (i.e. plasma NH 3 ) is necessary

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6 Objective: To determine the neonates diagnosed IEM and their outcomes in our hospital

7 IEM - METHODS Neonates diagnosed IEM in our NICU determined retrospectively January (3 years) Patients were regularly followed-up prospectively

8 Neonates consulted to metabolism-nutrition division; Neonatal encephalopathy of probable metabolic origin Unexpected / prolonged hypoglycemia Resistant metabolic acidosis Hepatic failure of probable metabolic origin Feeding intolerance Unexplained hypotonia Dysmorphic findings, hydrops fetalis

9 Standart laboratory analysis; Hemogram Blood sugar Arterial blood gases Liver - kidney functions Serum electrolytes Coagulation profile

10 Spesific laboratory analysis; Plasma NH 3 ; EDTA plasma by glutamate dehydrogenase Plasma - urine amino acids; automated ion-exchange chromatography with ninhydrine Urinary organic acids; gas chromatography - mass spectrometry Confirmation; Enzymatic studies of cultured fibroblasts or liver tissue, or molecular analysis

11 Glc > 250 mg/dl: insulin therapy (infusion) Hyperammonemia: Na-phenyl butirate iv, Na-phenyl acetate iv, N-carbamylglutamate iv, L-arginine hydrochloride iv-po, L-carnitine po, Sodium benzoate iv Acute metabolic crisis/encephalopathy: Emergent PD

12 Encephalopathy, resistant metabolic acidosis, feeding intolerance: Protein intake discontinued, TPN, high glucose infusion rate Hyperammonemia amino acidopathies: Proteinrestricted diet Prolonged jaundice & positive urine reducing substance: Lactose free nutrition

13 Developmental examination: Specialist of developmental pediatrics by the Guide for Monitoring Child Development (Ertem IE,Dogan DG, Gok CG, et al (2008). A Guide for Monitoring Child Development in Low- and Middle-Income Countries. Pediatrics 121(3);e581-e589. doi: /peds ) Neurologic examination: Pediatrician and neurologyst not aware of study

14 Statistical analysis; SPSS (Statistical Package for the Social Sciences) computer pocket program (13.0) Chi-square test relationship between factors affecting outcome Statistical significance p value < 0.05

15 Neonatal screening in Turkey; Phenylketonuria (1983) Congenital hypothyroidism (2005) Biotinidase deficiency (2008)

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17 IEM - RESULTS During 3 years; 45 neonates diagnosed IEM among 2600 hospitalized Ratio of IEM in our NICU: 1.73% Ratio of consanquinity 68.9% Sibling history 33.3%

18 Characteristics Result Gestational age (mean±st dev, min-max) 38.4±2.5 weeks (31-41) Birth weight (mean±st dev, min-max) 2987±588 g ( ) Age on admission (mean±st dev, min-max) days (0-45) Mother s age (mean±st dev, min-max) 27.9±6.4 years (19-43) Delivery route (vajinal/cesarean section) 20/25 (0.8) Gender (Female/male) 23/22 (1.1) Dysmorphic findings (n) (%) Major Minor (2%)4 (7.8%) 1 (2.2%) 3 (6.7%)

19 Admission complaints n (%) Poor feeding and/or inactivity Guthrie abnormalities Jaundice Respiratory abnormalities Vomiting Seizure History of another sibling with IEM Fever Non-immune hydrops fetalis 20 (44.4%) 8 (17.8%) 5 (11.1%) 3 (6.7%) 3 (6.7%) 3 (6.7%) 1 (2.2%) 1 (2.2%) 1 (2.2%)

20 Clinical characteristics n (%) Liver failure, coagulopathy 20 (44.4%) Resistant hypoglycemia 15 (33.3%) Lactate elevation 14 (31.1%) Resistant metabolic acidosis 11 (24.4%) Mechanical ventilation (n)(%) 26 (57.8%) Neoates treated with PD (n) (%) 14 (31.1%) Inotropic support (n) (%) One drug Multiple drugs 15 (33.3%) 8 (17.8%)

21 Indications to PD n (%) Toxic MSUD 4 (8.9%) Amino acid (leucine) Propionic acidemia 2 (4.4%) Metabolic acidosis Methyl malonic acidemia 2 (4.4%) Metabolic acidosis Citrullinemia 4 (8.9%) Amino acid (citrulline) Probable urea cycle disorder (UCD) 1 (2.2%) Elevated NH 3 Pyruvat carboxylase deficiency 1 (2.2%) Metabolic acidosis

22 IEM n (%) Amino acid disorders Phenylketonuria Maple syrup urine disease Non-ketotic hyperglycinemia Tyrosinemia Organic acidemias Propionic acidemia Methyl malonic acidemia Glutaric aciduria type.2 Disorders of UCD Citrullinemia Other 15 (33.3%) 8 (17.8) 5 (11.1) 4 (7.8) 2 (4.4) 8 (17.8%) 5 (11.1) 2 (4.4) 1 (2.2) 6 (13.3) 4 (8.9) 2 (4.4) Sugar intolerances; Galactosemia 4 (8.9)

23 Rare IEM n (%) Mitochondrial disorders - Pyruvat carboxylase def. 2 (4.4) Complex molecules synthesis/catabolism defects (Zellweger syndrome) Ketolysis defect (SCOT- Succinyl-Coa:3-ketoacid Coa transferase deficiency) 1 (2.2) 1 (2.2) Molybdenum cofactor deficiency 1 (2.2) Transcobalamin deficiency 1 (2.2) Congenital disorders of glycosylation type 1a 1 (2.2) Wolman disease 1 (2.2)

24 45 infants 8 died 41 infants discharged 4 died 3 lost to follow 1 followed by local unit 29 infants followed

25 Follow-up period was 2-42 months 17 infants were < 1 year old at last control

26 Percentile Weight (n) Head sircumference (n) Lenght (n) < 3% % %

27 Outcome n % Normal findings Exitus Developmental delay 9 20 Cerebral palcy (MSUD, UCD, PA, tyrosinemia) Lost to follow Followed by local unit Total

28 Factors affecting prognosis; Gestational age (p = 0.045) PD therapy (p = 0.008) Delivery route (p = 0.048)

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30 Conclusion: Incidence of IEM in our NICU is 1.73% IEM is not uncommon in NICU PICU Individually rare, collectively responsible significant neonatal morbidity and mortality Mortality is higher in neonates

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34 High mortality ratio (26.7%) and poor outcome suggested to be related the late admission, prematurity and PD Low mortality-morbidity (death / permanent neurological sequelae) is essential to early diagnosis and treatment (PD, hemodialysis) After suspicion, immediate reference of patient to an appropriate center (specific labaratory analysis)

35 NS is important in early diagnose, especially for the countries with high ratios of consanguinity Early diagnosis should be performed by expanded newborn screening, including very prematures Study limitation: Short follow - up period (2-42 months)

36 Thank you!