Inborn errors of metabolism are genetic disorders caused by defects in metabolic pathways. There are over 700 known conditions. Clinical features can include deterioration after apparent normalcy, parental consanguinity, unexplained seizures or encephalopathy, metabolic acidosis, vomiting, peculiar odor, or liver disease in pregnancy. Depending on presentation, inborn errors are classified into intoxication, energy failure, or storage disorder groups. Diagnosis involves blood and urine tests to check for abnormalities in glucose, ammonia, lactate, amino acids, fatty acids, and organic acids. Magnetic resonance imaging can also show characteristic findings for certain conditions.

1. Inborn Errors of Metabolism
Dr.Rajesh kumar

2. Introduction
• Inborn errors of metabolism (IEM) are disorders:
• due to block in the chemical pathways
enzyme,
cofactor, or
transporter deficiency
• Incidence of IEM vary widely and can be as high as 1 in 800
• Presently more than 700 conditions have been described
• High index of suspicion is essential
• Diagnosis is important for treatment and prognostication but also for
genetic counselling and antenatal diagnosis in subsequent pregnancie

5. • Deterioration after a period of apparent normalcy
• Parental consanguinity
• Family history of neonatal deaths
• Rapidly progressive encephalopathy and seizures of unexplained cause
• Severe metabolic acidosis
• Persistent vomiting
• Peculiar odor
• Acute fatty liver or HELLP (hemolysis, elevated liver enzymes & low
platelet counts) during pregnancy: seen in women carrying fetuses with
long-chain-3-hydroxyacyl-coenzyme dehydrogenase deficiency (LCHAD)

8. Clinical features

11. Acute liver disease
• This could manifest as: Jaundice alone-Gilbert syndrome, Criggler-
Najjar syndrome Hepatic failure (jaundice, ascites, hypoglycemia,
coagulopathy)- Tyrosinemia, galactosemia, neonatal
hemochromatosis, glycogen storage disease type IV
• Neonatal cholestasis: alpha-1 antitrypsin deficiency, NiemannPick
disease type C

12. • Hypoglycemia:
• persistent and severe hypoglycemia may be an indicator of an
underlying IEM. Hypoglycemia is a feature of galactosemia, fatty acid
oxidation defects, organic acidemias, glycogen storage disorders and
disorders of gluconeogenesis

13. • CARDIOMYOPATHY
• cardiomyopathy is a prominent feature in some IEM including fatty
acid oxidation defects, glycogen storage disease type II and
mitochondrial electron transport chain defects.

14. • Hypotonia:
• Although hypotonia is a common finding in any sick neonate, severe
global hypotonia can be the presenting feature of some of the
potentially treatable IEM including carnitine transport defect, fatty
acid oxidation disorder (FAOD), primary coenzyme Q (CoQ) defects,
neurotransmitter disorders, and riboflavin transport def

20. • Depending on the presentation,
• IEM are classified as
• Group 1 Intoxication group
• Group 2 Energy failure group
• Group 3 Storage disorder

25. Investigation
• 1) Complete blood count (neutropenia and thrombocytopenia seen
•
• in propionic and methylmalonic acidemia)
•
• 2) Arterial blood gas and electrolytes
•
• 3) Blood glucose
•
• 4) Plasma ammonia (normal values in newborn: 90 to 150 µg/dL or
•
• 64 to 107 µmol/L)
•
• 5) Arterial blood lactate (normal values: 0.5-1.6 mmol/L)
•
• 6) Liver function tests
•
• 7) Urine ketones
•
• 8) Urine reducing substances
•
• 9) Serum uric acid (low in molybdenum cofactor deficiency)

28. • In neonates with persistent hypoglycemia and suspected
• underlying IEM, presence of non-glucose reducing substances
• in the urine is suggestive of galactosemia. If there is no evidence
• of reducing substances in the urine, presence or absence of
• ketonuria would help diagnose the underlying condition: while
• the former would suggest glycogen storage diseases,
• gluconeogenic defects or organic acidemias, the latter (no
• ketonuria) would in dicate fatty acid oxidative defects,
• ketogenesis defects or hyperinsulinism.

35. • Very-long-chain fatty acids
• (VLCFA) elevation and low plasmologen suggests ZSD.
• Plasma transferrin isoelectric focussing detects certain CDG

39. • MRI findings have been described for
• MSUD : cytotoxic edema of myelinated white matter),
• PA and MMA (basal ganglia involvement), ZSD (polymicrogyria and
germinolytic cysts),
• ISOD (diffuse white matter involvement similar to HIE) and
• respiratory chain defect (symmetric putaminal involvement)