Inborn errors metabolism

(IEM)

Dr Lei Lei Win

IEM
IEMs may present as

• An acute metabolic emergency in a sick child.

• Chronic problems involving either single or multiple organs, either
recurrent or progressive, or permanent.
 They are mostly AR or X-linked
IEM
Screening for treatable IEM in a sick child
In an acutely ill child, IEM should be considered a differential diagnosis along with
other diagnoses:

• In all neonates with unexplained, overwhelming, or progressive disease

particularly after a normal pregnancy or birth, but deteriorates after feeding.

• In all children with acute encephalopathy, particularly preceded by vomiting,

fever or fasting.

• In all children with unexplained symptoms and signs of metabolic acidosis,

hypoglycaemia, acute liver failure or Reye-like syndrome.

• Prevention of IEM : screening all neonates for wide range of disorders

CLUES to IEM
• Unexplained death among sibling(s) due to sepsis or “SIDS”.
• Unexplained disorders in other family members (progressive
neurological disease).
• Consanguinity.
• Deterioration after a symptom-free interval in a newborn.
• Unusual smell - burn sugar (MSUD).
IEM with GLOBAL DEVELOPMENTAL DELAY (GDD)
General Management of IEM

• Restriction of dietary intake

• Replacement of missing enzyme, metabolite or cofactor

• Removal of toxic metabolite

• Transplantation of bone marrow or liver

General Management of IEM (Contd.)

• INITIAL APPROACH:

• Rule out non metabolic causes of symptoms like sepsis or asphyxia

• Consult geneticist or metabolic expert
• Do all tests eg blood , urine CSF
• Treat hypoglycemia /hyperammonemia

• Further management:
• Hydration / nutrition /correction of acidosis
• Stop all oral intake --to eliminate protein, galactose , fructose
General Management of IEM (Contd.)

• IV lipid after ruling out fatty acid oxidation disorders

• Hold protein till aminoacidopathy, organic academia corrected and urea

cycle defect excluded

• Special enteral formula and parenteral aminoacids are available

• Treat significant acidosis (pH <7.2) with continuous NaHCO3

• Elimination of toxic metabolites –haemodialysis

General Management of IEM (Contd.)

• Treatment of coexisting risk factor like sepsis, thrombocytopenia

• Cofactor replacement with vitamins like biotin for propionic

academia vit B12 for methylmalonic Acidemia and thiamine for
MSUD

• Neonates may be well and normal at birth. Then present with non
specific sign/symptoms. Common patterns are: vomiting, lethargy,
refusal of feed, hypotonia, drowsiness, unconsciousness and apnoea.
GALACTOSAEMIA
• AR
• Deficient galactose-1-phosphate uridyl transferase leads galactose
accumulation to liver, kidney brain.

• Manifests with poor feed, vomiting, jaundice, hepatomegaly .hepatic

failure , cataract and developmental delay when started with breast
feed or formula milk.

• Management with lactose and galactoe free diet.

• IQ < 80 even if treated
HOMOCYSTINURIA
• AR
• Cystathione synthatase deficiency.

• Developmental delay, learning difficulty, convulsion, subluxation of

lens.

• Marfan like structure.

• Fair complexion, brittle hair. Thromboembolic episodes.

• Responds to large doses of pyridoxine. May need low methionine diet

with cysteine in addition with re-methylating agent betaine.
PHENYLKETONURIA
• AR.

• Due to deficiency of phenylalanine hydroxylase or defect in biopterin

synthesis or recycling.

• Presents with dev delay, musty odour, fair haired, blue eyed, may
have eczema and seizures.

• Guthrie test detects earlier.

• Treatment—dietary phenylalanine restriction-life long.

GLYCOGEN STORAGE DISEASE-GSD
• AR.
• Prevents mobilization of glucose from glycogen.
• So abnormal accumulation of glycogen in liver/muscle.
• 9 types.
• Pompes disease type II –severely affects heart –cardiomyopathy.
• Von Gierkes disease—type I liver mostly affected.

• May have hypoglycemia and hepatomegaly.

• Management—frequent feeds to avoid hypoglycemia.
• In pompes –myozyme enzyme replacement
FAMILIAL HYPERLIPIDEMIA
• AD
• Risk factor for coronary heart disease.
• Defect in LDL receptor.
• if serum LDL is >3.3mol/L or serum cholesterol > 5.3mmol/L to do
HDL. Xanthoma may be present.
• Treatment is bile acid sequestrants, HMG-CoA reductase inhibitors-
the statins.
• Fenofibrate also tried.
• May need liver transplant ,so referral to specialist centre
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