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PICU Considerations of Inborn error of metabolism
- 1. IEM in critical care PRESENTER- DR. SIDDAN MODERATOR : DR. MANAS SIR
- 2. Objectives Introduction Critical care concerns Basic pathophysiology Case scenario Laboratory evaluation Emergency management Post mortem evaluation Take home message
- 3. Inborn error of metabolism Hereditary diseases that disrupt normal biochemical processes Individually rare, but collectively common (Incidence of 1:1500 livebirth) Wide range in severity of presentation and time of onset Severe IEM usually present in newborn period or infancy, milder - later in childhood and even in adulthood The presentation most metabolic conditions are non specific
- 4. Inborn error of metabolism 1. Accounts for about 2-5 % of PICU admission. 2. Most common presentation is neurological (60%) 3. Diagnosis is important not only for treatment and prognostication 4. Genetic counselling and antenatal diagnosis in subsequent pregnancies
- 8. Mechanism of ammonia toxicity
- 10. Case scenario 1 A 1 year old female infant apparently well till last 3 days, was started on cerelac recently. Child started having of multiple episodes of vomiting and irritability. Later child developed lethargy and abnormal breathing. On examination Acidotic breathing GCS: E2V2M4 which progressed to E1V1M4 Hepatomegaly Chest- clear
- 11. Initial evaluation ABG pH: 6.98 PCO2: 23 HCO3: 3 Na: 142 Cl: 104 Lactate 1.3 AG 35 Ketones 4+ RBS 162mg/dl Ammonia 342 Organic acidemia Mitochondrial disorders
- 12. Case scenario 2 A 1 month old male infant apparently well till last 1 week. Currently mother c/o decreased feeding and activity. For last 2 days child also has fast breathing and feeding diaphoresis. O/E: HR: 190/min, RR: 73/min Lethargic Hepatomegaly + Chest- bilateral basal crept
- 13. Initial evaluation ABG pH: 7.12 PCO2: 26 HCO3: 8.2 Na: 139.2 Cl: 100 Lactate 4 AG 31 Ketones nil RBS 32mg/dl Ammonia 129 POCUS Echo Poor cardiac contractility Fatty acid oxidation disorder
- 14. Cardiomyopathies in IEM Diagnostic Approaches to Pediatric Cardiomyopathy of Metabolic Genetic Etiologies and Their Relation to Therapy Gerald F. Cox, MD, PhD
- 15. Cardiomyopathies in IEM Cardiac Manifestations in Children with Inborn Errors of Metabolis: Kyriaki papadopoulou-legbelou, maria gogou and athanasios evangeliou
- 16. Case scenario 3 A 4 year old male child apparently well till last 1 week presented with c/o left sided upper and lower limb weakness. He has past h/o similar episode 2 year back but on right side and associated with generalised seizure. O/E: Lethargic Left sided hemiparesis Short stature and underweight
- 17. Initial evaluation ABG pH: 7.22 PCO2: 32 HCO3: 14 Na: 139.2 Cl: 100 Ketones nil RBS 71mg/dl Ammonia 120 Lactate 10 SGOT SGPT 179 244 MELAS
- 18. IEM Presenting as stroke/stroke like episodes
- 19. Case scenario 4 A 1 year old female infant apparently well till last 15 days presented with c/o recurrent easy bruising all over the body and lethargy since morning. Mother also complains that child not gaining weight since early infancy. Her elder sibling died due to some unknown liver disease. O/E: Icterus +, HR: 98/min Failure to thrive present, Developmental delay Hepatomegaly
- 20. Initial evaluation PT/APTT >120 sec/87 Platelet 2.1 lakh RBS 28 mg/dl SGOT SGPT TB/DB TP/Albumin 106 98 13/8.9mg/dl 3.8/1.7 Alpha fetoprotein 30000IU/ml TYROSINEMIA
- 21. Metabolic Liver Diseases Presenting as Acute Liver Failure in Children SEEMA ALAM AND BIKRANT BIHARI LAL From Department Of Pediatric Hepatology, Institute Of Liver And Biliary Sciences, New Delhi, India
- 22. Case scenario 5 A 1 month old female infant apparently well till last 15 days, was referred from outside hospital I/v/o recurrent low sugar records and feed intolerance. At presentation child had fever and decreased activity O/E: HR: 175 with poor peripheral pulses and cold peripheries Cataract Hepatomegaly Hypotonia
- 23. Initial evaluation SGOT SGPT 190 200 PBS Haemolytic picture RBS 30 mg/dl Blood c/s Klebsiella pneumonia Urine dipstick negative Urine for reducing substance Negative Galactosemia
- 24. Why Gram negative sepsis in Galactosemia?
- 25. Case scenario 6 A 1 year old female infant was referred from outside hospital I/v/o difficulty in weaning from ventilator. The child was intubated in CO2 narcosis. Hospital records shows there was difficulty in intubation. Past history: Recurrent chest infections Failure to thrive Developmental delay with vision disturbance
- 27. What are causes of CO2 retention? What are the causes of difficult airway? Ventilatory issues in current condition?
- 30. Case scenario 7 An 1 year old infant presented with status epilepticus. In emergency seizure did not responds to first and second line antiepileptics. Child was started on midazolam infusion and shifted to PICU. On reviewing the history child has developmental delay, recurrent early morning seizures O/E Microcephaly Failure to thrive
- 31. Initial evaluation EEG Epileptiform discharges in the background of generalised slowing MRI Brain Enlarged perivascular spaces, enlarged ventricles, and delayed myelination RBS 90 mg/dl CSF cytology Acellular CSF Sugar CSF Protein CSF culture 03mg/dl 69mg/dl sterile GLUT 1 Deficiency
- 34. Case scenario 8 A 15 year old female child presented to emergency with c/o acute pain abdomen. Outside USG was s/o appendicitis. USG done at AIIMS was s/o mild oedema of appendix. Child undergone appendectomy, but pain abdomen did not subside. No evidence of post operative infection. CECT abdomen s/o post operative changes. On POD 3 child developed 2 seizure episode and she became very irritable. Pediatric medicine opinion was taken. On evaluation child found to have Sodium of 118, mildly elevated liver enzymes and pancreatic enzymes Treated as symptomatic hyponatremia.
- 36. Case scenario 9 An 5 year old male child presented with recurrent fall attacks following sudden jerky movements for last 1 year. There is also h/o decreased vision, recurrent seizure and loss of achieved milestones. At presentation in emergency child was in status epilepticus which was aborted after antiepileptics. O/E Retinal dystrophy Extrapyramidal movements
- 37. Progressive myoclonic epilepsy - NCL
- 38. Case scenario 10 A 1 year old male infant presented with c/o fever for 5 days, decreased oral intake and activity for 1 day. Child had not passed urine for last 12 hour. Was admitted to outside hospital for 1 day and received some IV medication O/E: HR: 178/min Cold peripheries, low pulse volume Hepatomegaly present Lethargic
- 39. Initial evaluation ABG pH: 7.28 PCO2: 33 HCO3: 16 Na: 142 Cl: 104 Lactate 6.3 Ketones trace RBS 52mg/dl Blood c/s Staphylococcus aureus Not to forget basics – Its Septic shock
- 41. In General Family history Consanguinity Failure to thrive Recurrent episodes/Fluctuating course Dysmorphism Abnormal body/urine odor Hepatosplenomegaly
- 42. • Neuroregression • Tone abnormalities • Ophthalmological features • Profound encephalopathy • Hiccups • SRSE • HELLP Syndrome in mother • Hepatosplenomegaly • Non ketotic Hypoglycaemia • HOCM • Hypotonia and muscular weakness • Infancy • Arrythmia • Neonatal ALF • Relation to feed • Disproportionate encephalopathy • Failure to thrive • Recurrent vomiting • Coagulopathy at onset Seizure Cardiogenic shock Liver disease When to suspect IEM in Systemic manifestations?
- 43. Respiratory manifestations in patients with inherited metabolic diseases Francesca Santamaria, Silvia Montella, ERS Journal
- 44. Haematological findings in children with inborn errors of metabolism Betul Tavil · Hatice Serap Kalkanoglu Sivri
- 47. Testing pitfalls At least 5 mL plasma and 5 mL urine should be set aside before correction of metabolic abnormalities Studies such as plasma amino acids, plasma acylcarnitine profile, and urine organic acids need to be sent to a specialized laboratory, they should be sent by overnight courier. Delay affects results Ammonia values can be significantly elevated if the sample is not immediately rushed on ice to the laboratory and analyzed Lactate and pyruvate concentrations must be obtained simultaneously for comparison
- 51. Neuroimaging in IEM- When to suspect IEM? Symmetric brain disease Isolated or preferential involvement of the brainstem and/or cerebellum Changes mimicking HIE Acute on chronic lesions Volume loss/progressive atrophy MRS- relevant metabolic ratio
- 52. Immediate management Stabilize circulation, airway, and breathing Treat hypoglycemia to prevent catabolism Remove toxic metabolites Correct metabolic acidosis Provide cofactors Additional therapies in selected patients
- 53. Disease Empiric Cofactor therapy Urea cycle L-Arginine 600 mg/kg IV and 200-600 mg/kg/d Sodium benzoate 250 mg/kg IV and 250 mg/kg/d Sodium phenylacetate 250 mg/kg IV and 250 mg/kg/d Sodium phenylbutyrate 100- 200 mg/kg PO tid Biotinidase deficiency and multiple carboxylase deficiency Biotin 5-10 mg/d PO MMA and methionine synthase deficiency Hydroxocobalamin 1-5 mg/d IM/IV
- 54. Disease Empiric cofactor therapy Mitochondrial disorders Coenzyme Q10 25 mg tid PO Carnitine 50 mg/kg bid IV/PO Alipoic acid 100 mg q.d. PO/IV B complex vitamins 100 mg each q.d. PO Vitamin E 50 units q.d. PO Propionic academia/MMA Metronidazole 15 mg/kg/d divided q8-12 h PO/IV Ketotic hyperglycinemia Sodium benzoate 250 mg/kg IV and 250 mg/kg/d MSUD Thiamine 150 mg/d IV/PO; >3 y 300 mg/d
- 55. Disease Drugs Mitochondrial disorders Lactate containing fluids propofol Glycogen storage diseases V ( McArdle disease) and VII ( Tauri disease) Depolarizing neuromuscular blocker (succinylcholine) FAOD Propofol Drugs to avoid during certain IEM
- 58. Weiner DL. Metabolic emergencies. In: Textbook of pediatric emergency medicine, 5th ed, Fleisher GR, Ludwig S, Henretig FM (Eds), Lippincott, Williams and Wilkins, Philadelphia 2006. p.1193. IV Bicarbonate in severe metabolic acidosis?
- 62. Take home messages Suspicion is the key Always take extra samples before starting treatment Group based approach- Goal is to manage the case: not final diagnosis Toxin removal- No other option Metabolic autopsy case of death
- 63. References
- 64. THANK YOU…