Area of special interest Inborn Errors of Metabolism ... · Dr. A.Radha Rama Devi, M.D Consultant,...
Transcript of Area of special interest Inborn Errors of Metabolism ... · Dr. A.Radha Rama Devi, M.D Consultant,...
Dr. A.Radha Rama Devi, M.D
Consultant, Sr Paediatrician & Clinical Geneticist & President of Indian Society of Inborn Errors
Rainbow Children Hospital & Dr Reddys Institute of Life Sciences, University of Hyderbad
Sandor Speciality Diagnostics Pvt Ltd, Hyderabad
Area of special interest: Inborn Errors of Metabolism & Newborn Screening
Awards and honours : President Medal In MBBS; Gold medal in Medicine
British council Travel fellowship, UK.
Life time Achievement award in Inborn errors of Metabolism by the
Hyderabad branch of Indian academy of Paediatrics.
Senior Women Bio-scientist: Department of Biotechnology (2005)
Top 10 women in Medicine (2007)
Dr. I. C.Verma Outstanding Researcher Award- 2018
Sandor Oration Award- ISIEM,Pune,2019
Achievements: Started the first large scale New-born Screening in India.
How do I manage Suspected Inborn error of metabolism?
Dr.A.Radha Rama Devi
Rainbow children Hospital
Hyderabad
Inborn errors of metabolism – Points to remember
• With appropriate therapy, patients may completely recover without sequelae
• Early diagnosis is a prerequisite for effective treatment,
• Neonatal screening plays an important role in early diagnosis,
• Tandem mass spectrometry has increased the number of diseases that can bedetected.
Management of IEM-From diagnosis to prevention
• Includes
• Clinical presentation
• Biochemical diagnosis
• Molecular confirmation
• Treatment including Novel therapies.
• Family screening
• & Prevention
•
• PND
Management of IEM
Is a combination of 3 aspects – Nutritional Supplements, Dietary
Modifications and Medical Care.
Diet is the sole form of therapy or
used in combination with other
treatments
Cell therapy
Transplant
• Remember 75% of IEMs are treatable!
Principles of Management
• Treatment of patients with a known IEM should be disease and patientspecific.
• Management includes critical care and follow up care and prevention
• Strict adherence to dietary and pharmacologic treatment life long
• Avoid precipitating factors and stresses to prevent acute
decompensation
Follow treatment protocols developed by an IEM specialist.
Provide Instructions for resuscitation measures in an acute crisis.
Medical Care
Emergent treatment
• Critical management is similar to any other disease
• Establish airway, breathing, circulation
• Discontinue oral intake in patients with encephalopathy and
vomiting for the first 24-48hours
• Address associated complications – hypoglycaemia, MA,
Hyperammonemia.
Metabolic acidosis
• Correct electrolyte abnormalities.
• Add electrolytes at maintenance concentrations,
• Sodium bicarbonate or, if the patient is hypokalemic, potassium acetateshould be administered.
• Rapid correction or overcorrection may have paradoxical effects on theCNS.
• For intractable acidosis, consider haemodialysis // peritoneal dialysis.
Metabolic complications-Hypoglycemia
• IV dextrose bolus, as D10 for neonates and D10 or D25
beyond the neonatal period, followed by continuous IV
administration of dextrose.
• Prevent catabolism, and promote urinary excretion of
toxic metabolites
• High-volume maintenance fluid will also promote urinary
excretion of some toxic metabolites.
• Add insulin, 0.2-0.3 IU/kg, as needed to maintain glucose
level in the desired range.
Hyperammonemia
• Significant hyperammonemia is life-threatening and must
be treated immediately.
• To reduce ammonia, sodium benzoate 250mg/kg
• Ammonia level >500-600 mg/dL, hemodialysis
• If hemodialysis is not available, peritoneal dialysis (< 10% as effective as hemodialysis)
• or double volume exchange transfusion (even less effective)
Inpatient care :
• Once toxic metabolites have been normalized & able to tolerate enteral feeding, protein is reintroduced as an essential amino acid solution,
• initially at 0.5-0.75 g/kg/day and gradually increased.
• Include natural protein 0.8gm/kg/day in the form of breast milk or regular milk(never stop natural protein totally). Will cause symptoms of malnutrition
• Required calories/day is met with protein free formula foods.
Pharmacologic therapy
• To increase activity of abnormal cofactor-dependent
enzymes (e.g., thiamine [B-1] 5-20 mg/day PO up to 500
mg/day,
• biotin 5-20 mg/day PO,
• riboflavin [B-2] 200-300 mg PO tid,
• cobalamin [B-12] 1-2 mg/day IM) may be given.
Follow up
• Regular follow up is essential
• Evaluate growth & development
• Periodically monitor the levels of the metabolites either in urine or blood based on the type of the disorder.
• Adjust dietary requirement as per the weight and age.
• Medical therapy to be continued life long
Extended treatment
• Transplantation (organ or bone marrow)
• Enzyme replacement therapy
• Prevention & Counselling
OTC def
Liver Transplant
4yr girl
Rec Hyperammonemia >600Umol.
Rpted hospitalistion
Growth failure
Behavioral changes
Molecularly confirmed OTC gene mutation
Underwent pediatric cadaver transplant
2yrs post transplant, normal ammonia
On regular diet
Attending school
ERT IN GAUCHER TYPE I
• Management of a Known IEM
A case of organic aciduria
• As a representative for all IEMs management
• From Diagnosis- NBs
• Management
• Prevention
• 3months baby
• Irritability, refusal to feed
• Encephalopathy
• Hypoglycemia, hyperammonemia, met acidosis
• Managed in the ICU
• Follow-up with MMA diet, had two decompensation events and managed.
• Doing well, aged now 11yrs
• Family counselling, specific gene identified
• Provided PND in the next pregnancy.
A case of MMA- Sequence of management
MRI
Batwing appearance
Sylvian fissure
Child with Glutaric Aciduria Type I
35days old female infant born to 1st cousin couple.
Macrocephaly, (intrauterine)arachnoid cyst, Subdural
hematoma
NBS detected elevated C5DC in TMS(2.0/<0.7)
Neurosonogram Small cyst near the ventricles, minimal
internal hydrocephalous. AF wide patent bulging
Urine organic acids & mutation study confirm GAI
Diet replacement since 3rd week of life Normal
development Presently aged 12 yrs.
PND done in next pregnancy. Normal fetus
Late diagnosis
Severe Movement disorder
Dystonia
Wheel chair bound
ID with high GA levels
Second child affected ,diagnosed at 11
months
No follow-up
Caution:
Watch for tryptophan deficiency
symptoms during diet management.
Citrllinemia
IVA
IVA
MMAMMA
MMA
PKU
GA1
Take Home message
• DO NEW-BORN SCREENING TO ALL NEONATES
• DO METABOLIC SCREENING TO ALL HIGH RISK BABIES
• DO METABOLIC SCREENING TO ALL BABIE BORN TO RELATED PARENTS & PARENTS WITH BAD OBSTETRIC HISTORY
Give the required treatment for the specific disorder
Positive counselling and PND in subsequent pregnancies and
to their immediate families.