Management of IEM
-
Upload
sathish-kumar -
Category
Documents
-
view
227 -
download
0
Transcript of Management of IEM
-
8/2/2019 Management of IEM
1/41
Dr.Lakshmi.L
-
8/2/2019 Management of IEM
2/41
Treatment Initial Emergency management
Definitive
-
8/2/2019 Management of IEM
3/41
Emergency managementInitial ED treatment does not require knowledge of the
specific metabolic disease or even disease category.
1. Establishment of ABC
2. Correction of acute metabolic derangements
-
8/2/2019 Management of IEM
4/41
Emergency managementAs In any critically ill child establish a stable
airway, breathing, and circulation
Metabolic correction includes:
Correction of Hydration
Correction of biochemical abnormalities Metabolic acidosis
Hypoglycemia
Hyperammonemia
-
8/2/2019 Management of IEM
5/41
Metabolicderangements
Accumulation
of toxicmetabolites
Loss ofsubstrate
mixed
-
8/2/2019 Management of IEM
6/41
Metabolicderangements
Accumulation
of toxicmetabolites
Loss ofsubstrate
mixed
correction ofmetabolicabnormalities
-Elimination of
toxic metabolites-prevention offurther formationof toxicmetabolites-cofactor
administration
Provision ofadequate substrate
-
8/2/2019 Management of IEM
7/41
Goals of the initial treatment for patients with an inborn error of metabolism
correction of metabolic abnormalities, and
Elimination of toxic metabolites
prevention of further formation of toxic metabolites Administration of Adequate calories
Treatment of precipitating factors when possible
Institute co factor therapy
Even the apparently stable patient with mild symptoms maydeteriorate rapidly with progression to death within hours.
With appropriate therapy, patients may completely recoverwithout sequelae.
-
8/2/2019 Management of IEM
8/41
Correction of hypoglycemia
Hypoglycemia is one of the common manifestation of
many IEMs. Every attack of hypoglycemia is detrimental to the
growing brain.
Further more One of the goals in IEM management is
to prevent catabolism and establish anabolic state So Correction of hypoglycemia is paramount
important in newborn with IEM
-
8/2/2019 Management of IEM
9/41
Hypoglycemia in Galactocemia
GSD
Gluconeogenic defects OA
FAO deffects
Ketogenesis defects
Fructose-1,6-diphosphatase deficiency
Hereditary fructose intolerance
-
8/2/2019 Management of IEM
10/41
Correction of hypoglycemia Hypoglycemia corrected by IV dextrose bolus, 10%
dextrose in newborn, 25%dextrose in older infants
0.25-0.5 g/kg/dose (1-2 mL/kg); not to exceed 25 g/dose, and
followed by continuous IV administration of dextrose.
For all patients in whom an IEM cannot be ruled out, givedextrose 10-15% IV at a rate high enough (1 to 1.5maintenance) to prevent catabolism (8-10 mg/kg/min).
A target glucose of 120 170 mg/dl is maintained If necessary Add insulin 0.2-0.3 IU/kg, as needed to
maintain normoglycemia.
-
8/2/2019 Management of IEM
11/41
Correction of dehydration This enables us to achieve adequate renal perfusion
and elimination of toxic metabolites
Shock if present is corrected with normal saline Dehydration with 5DNS
Hypotonic fluids are avoided in view of developmentof cerebral edema
-
8/2/2019 Management of IEM
12/41
Treatment of acute acidosis
Acidosis in IEM Could beorganic acidemia
congenital lactic acidosis
-
8/2/2019 Management of IEM
13/41
Organic acid acidosis Defects in Organic acid metebolism
Fatty acid oxidation disorders
Defects in ketone metabolism Ketothiolase deficiency
Succinyl-CoA: 3-ketoacid-CoA transferase deficiency
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
-
8/2/2019 Management of IEM
14/41
Primary Lactic acidosis Primary lactic acidoses
Pyruvate dehydrogenase complex deficiency
Pyruvate carboxylase deficiency Phosphoenolpyruvate carboxykinase deficiency
Mitochondrial respiratory/electron transport chaindefects
-
8/2/2019 Management of IEM
15/41
Treatment of acidosispH 7.35-7.457.1 7.35, asymptomatic- frequent review of the metabolic
parameterspH 7.1 deteriorating Sodium bicarbonate starting with half correction (base deficit
*weight*0.3)/2 Administered slowly(0.35-0.5mEq/kg/hr (max 1-2mEq/kg/hr)) Review frequently Monitor potassium
When potassium is low and patient symptomatic potassiumcorrection given (1 mEq/kg/h)
Intractable acidosis needs hemodialysis
-
8/2/2019 Management of IEM
16/41
Organic acidemia Kept nil oral
Iv glucose
Supportive care L-Carnitine: 100mg/kg/day iv or oral
Vitamin cocktail
Biotin 10mg/day oral
Vitamin b12 1-2mg/day im
Thiamine 300mg/day iv
-
8/2/2019 Management of IEM
17/41
Management of congenital lactic
acidosis Supportive care
L-carnitine: 50-100 mg/kg orally
Vitamin cocktail Thiamine: up to 300 mg/day in 4 divided doses.
Riboflavin: 100 mg/day in 4 divided doses.
Biotin 10 mg/day. (Biotin responsive Multiple
carboxylase deficiency may present with unexplainedlactic acidosis)
Add co-enzyme Q: 5-15 mg/kg/day
-
8/2/2019 Management of IEM
18/41
Hyperammonemia Urea cycle disorders
THAN
Congenital lactic acidosis Organic acidemias
FAO defects
-
8/2/2019 Management of IEM
19/41
Treatment of hyper ammonemia
Normal blood ammonia levels 10-40 mcmols/l Significant hyperammonemia is life threatening and must be
treated immediately upon diagnosis.1. Stop all feeds2. Supportive care3. Give adequate glucose/iv lipids to provide adequate calories
and prevent catabolism4. Administration of sodium phenylbutyrate and sodium
benzoate(alternate pathway for nitrogen excretion)
5. Arginine in hyperammonemia without acidosis(urea cycledefects except arginase deficiency), an infusion of 6 mL/kg of10% arginine HCL (0.6 g/kg) can be given intravenously over90 minutes.
6. L-carnitine-200mg/kg/day
-
8/2/2019 Management of IEM
20/41
Sodium benzoate (ivor oral)
250 mg/kg loadingdose
250-400mg/kg/dayin 4 div doses
-
8/2/2019 Management of IEM
21/41
Sodiumphenylacetate
LD-250mg/kg
250-500mg/kg/day
-
8/2/2019 Management of IEM
22/41
Hemodialysis
For ammonia greater than 500-600 mcg/dL,
if comatose or ventilator-dependent evidence of cerebral Edema
Levels >300 mcg/dl after ammonul treatment
Two to 3 days of therapy is usually necessary. The goalof HD is to achieve a plasma ammonia concentrationof
-
8/2/2019 Management of IEM
23/41
If hemodialysis is not readily available, peritoneal dialysis(< 10% as effective as hemodialysis) or double volumeexchange transfusion (even less effective) can be
performed while arrangements are made to transport toa center where hemodialysis is possible, as long as thisdoes not delay transfer.
-
8/2/2019 Management of IEM
24/41
Refractory seizures -suspected
metabolic etiology If patient persists to have seizures despite 2 or 3
antiepileptic drugs in adequate doses,
consider trial of pyridoxine 100 mg intravenously.
give trial of biotin 10 mg/day and folinic acid 5mg twicedaily (folinic acid responsive seizures).
Trial of pyridoxal phosphate 10 mg/kg/dose X 2 doses isalso recommended, however this is not available inIndia.
glucose transporter defect- responds to the ketogenicdiet
-
8/2/2019 Management of IEM
25/41
Further Inpatient Care Once initial stabilization attained and toxic
metabolites have been normalized For amino and organic acidopathies and urea cycle defects,
protein intake should be restricted to 40-50% ofrecommended daily allowance (RDA).
Lipids, 2-3 g/kg/d as 20% intralipid, can be given to increasecaloric intake, but they are contraindicated for certain fattyacid oxidation defects.
For patients able to tolerate enteral feeding, protein-restrictedpreparations may be given.
With definitive diagnosis, specific dietary regimens, availablefor most inborn errors of metabolism should be initiated.
-
8/2/2019 Management of IEM
26/41
Definitive treatment Dietary Restriction
Supplement deficient products
Stimulate alternate pathway Supply vitamin co-factor
Transplantation (organ or bone marrow)
Enzyme replacement therapy
Gene therapy
-
8/2/2019 Management of IEM
27/41
Long term treatment of IEM Medical therapy specific for the inborn error of
metabolism diagnosed will need to be continued,usually for life.
Long-term, routine follow-up screening should beprovided for potential disease complications
-
8/2/2019 Management of IEM
28/41
Dietary treatment Strict adherence to dietary and pharmacologic
regimen is recommended for patients diagnosed withan inborn error of metabolism.
-
8/2/2019 Management of IEM
29/41
Galactosemia
lactose-restricteddiet for their entirelives
Glycogen storage disorders
The mainstay of therapy isfrequent feedings and
restriction of lactose andsucrose
-
8/2/2019 Management of IEM
30/41
Elimination ofdietary fructose andsucrose
HF
intolerance
Glucoseadministration
L-carnitine suppleFatty acidoxidation
defects
-
8/2/2019 Management of IEM
31/41
homocystinuria PKU
MSUD
indigenous diets basedon aminoacid contentof the diet
-
8/2/2019 Management of IEM
32/41
Enzyme replacement ERT is now commercially available for some
lysosomal storage disorders.
However, these disorders do not manifest in thenewborn period, an exception being
Pompes disease (GSD Type II) which may presentin the newborn period and for which ERT is now
available
-
8/2/2019 Management of IEM
33/41
COFACTOR REPLACEMENT
THERAPY The catalytic properties of many enzymes depend on
the participation of non protein prosthetic groups,such as vitamins and minerals, as obligatorycofactors. The following co-factors may be beneficialin certain IEM
-
8/2/2019 Management of IEM
34/41
Methylmalononic acidemia, homocystinuria, Vitamin B12
Holocarboxylase synthetase deficiency, Biotinase deficiency, biotin
Mitochondrial disorders, PDH def thiamin
Homocystinuria, xanthurenic aciduria, primary hyperoxaluria,Pyridoxin responsive fits, hyperornithemia
Pyridoxine,Pyridoxalphosphate
Hereditary orotic aciduria, Methionine synthase deficiency,
Cerebral folate transporter deficiency, hereditary folatemalabsorption,Kearns-Sayre syndrom
Folinic acid
Glutaric aciduria Type I, Type II, mild variants of ETF, ETFDH,complex I deficiency
Riboflavin
-
8/2/2019 Management of IEM
35/41
Organ transplantation Hematopoietic stem cell transplantation
Hepatocyte transplantation
-
8/2/2019 Management of IEM
36/41
Gene therapy The genetically defective function will be restored by
transfer of a normal gene into somatic cells.
The therapeutic potential and safety of gene therapyhas been explored in cultured cells and experimentalanimals,
but therapeutic clinical trials have not yet been
proposed or performed in humans
-
8/2/2019 Management of IEM
37/41
Prevention Genetic counselling
Prenatal screening
-
8/2/2019 Management of IEM
38/41
Prognosis Prognosis varies based on individual inborn error of
metabolism (IEM) and may differ for different forms ofa particular IEM.
A high index of suspicion is critical for early diagnosisand treatment of IEM.
Rapid treatment may be life saving and often results in
full recovery.
-
8/2/2019 Management of IEM
39/41
Patient Education Provide education regarding disease and patient care
(manifestations, course of disease, treatment,psychosocial support) as appropriate.
Provide genetic counseling to discuss recurrence risks,screening of other family members, and prenataldiagnosis.
Provide information regarding support groups.
National Organization of Rare Diseases (NORD) candirect families to resources for more than 1000 IEMs.Professional and peer support groups exist for manyIEMs.
-
8/2/2019 Management of IEM
40/41
conclusionDont think of IEM as rare, exotic and untreatable
disorders.
Think of IEM in sick newborns in parallel with othercommon conditions
Even if the chances of survival appear less, everyattempt must be made to reach a diagnosis so that
parents can be guided for future pregnancy
-
8/2/2019 Management of IEM
41/41