Recognition of the Infant/Child with Inborn Errors of Metabolism (IEM)

Question 1

What types of presentation would we see indicating IEM before birth?

Answer 1

–Hemoglobinopathies leading to hydrops fetalis

Question 2

What type of presentation would you look for at birth representing IEM?

Answer 2

Congenital lactic acidosis

Question 3

What types of IEM often cause sudden death at ~2-3 days?

Answer 3

Defects in fatty acid oxidation

Question 4

If you see a baby suddenly deteriorate after a symptom free period what might you think?

Answer 4

Adrenal insufficiency

Question 5

What are the endocrine causes of hypoglycemia in infancy?

Answer 5

1. –Adrenal insufficiency
2. –Growth hormone deficiency
3. –Hypothyroidism
4. –Hyperinsulinemia
5. –Hypopituitarism

Question 6

What are the metabolic causes of hypoglycemia in infancy?

Answer 6

1. Disorders of carbohydrate metabolism
2. Disorders of gluconeogenesis
3. Disorders of organic acid metabolism
4. Disorders of fatty acid oxidation and carnitine transport

Question 7

What are some “other” causes of hypoglycemia in infants?

Answer 7

Drugs - oral hypoglycemics/alcohol/aspirin

Sepsis

Question 8

–Infants presenting with hypoglycemia associated with lethargy, hepatomegaly and liver failure, cardiomyopathy and/or dysrhythmia may have what kind of defect?

Answer 8

a fatty acid oxidation defect

Question 9

•When evidence of liver failure remains despite correction of hypoglycemia, three disorders must be considered urgently, what are they?

Answer 9

–Galactosemia
–Hereditary fructose intolerance
–Tyrosinemia type I

Question 10

When considering a diagnosis of…

–Galactosemia
–Hereditary fructose intolerance
–Tyrosinemia type I

What must be excluded from the diet until an exact diagnosis can be made?

Answer 10

galactose , fructose and protein must be excluded from the diet until an exact diagnosis can be made

Question 11

Infants presenting with hypoglycemia that maintain normal glucose levels with permanent glucose provision without signs of liver failure with hepatomegaly may have what glycogen storage diseases?

Answer 11

Type I

Type III

fructose-1,6-biphosphatase defects

Question 12

Infants that cannot maintain adequate glucose levels despite constant glucose provision and without evidence of ketoacidosis most likely will have?

Answer 12

Hyperinsulinemia

Question 13

What are the two most common presentations of neurological deterioration?

Answer 13

Seizures

Hypotonia

Question 14

What can neurological deterioration be caused by?

Answer 14

Variety of conditions including…

1. organic acidemias
2. urea cycle defects
3. maple syrup urine disease
4. fatty acid oxidation defects
5. congenital lactic acidosis

Question 15

What is the rate of neurological deterioration dependent upon?

Answer 15

Nature and severity of defect. Well no shit.

Question 16

When do urea cycle and branched chain organ acidemias typically appear?

Answer 16

12-72 hours of age

Question 17

When does maple syrup urine disease appear?

Answer 17

4-7 days of age

Question 18

When does hyperglycemia appear generally?

Answer 18

48 hours of age

Question 19

A 2-year–old girl was brought to the ED after collapsing at home. She had been playing outside when she began to feel unwell. Shortly thereafter she collapsed but remained conscious but drowsy. Her parents transported her by car to the ED and while in route the girl had several self-limiting generalized seizures.

There was no history of head trauma or fever. She was born at full term with no perinatal complications. The family history was noncontributory. She had reached all of her developmental milestones.

Upon arrival at the ED she was unconscious with apneic spells and a heart rate of 50 beats/minute. CPR was initiated and her airway secured. Intraosseous lines were inserted and after 2 minutes of CPR asystole developed. Epinephrine and atropine were administered with a bolus of 0.9% saline. A glucose level of < 0.5 mmol/L was noted. A bolus of 5ml/kg of 10% dextrose was administered and the recheck of her blood glucose was reported at 7.7mmol/L. A strong pulse was palpated and sinus tachycardia was present.

• CT of the brain was normal
• Ebstein-Barr virus (EBV) IgM antibodies were strongly positive
• Toxicology screening was negative
• Metabolic screening including plasma amino acids, urine organic acids and plasma acylcarnitine profiling was performed

What’s the problem?

Answer 19

Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)