Approach to metabolic diseases

Question 1

What are the cases of high ammonia?

Answer 1

Very high >1000 - urea cycle defects (OTC deficiency) (no acidosis. Do plasma AA)
Organic acidopathies (if metabolic acidosis)
Aminoacidopathies
Fatty acid oxidation defects (in older child)

Hypercatabolic state, protein load, severe liver disease, patent ductus venosis, prem babies with resp problems in first 24 hours.

Question 2

How are metabolic diseases roughly classified?

Answer 2

Small molecule disorders (mainly acute encephalopathy)

Diseases of organelles

Question 3

What are four initial markers you look for in metabolic disorders?

Answer 3

1. Acid base balance
2. Ammonia
3. Glucose
4. Ketones

Question 4

What are the biochemical markers of amino acidopathies?

Answer 4

Metabolic acidosis with high anion gap
normal ammonia
low glucose
Ketones ++

Question 5

What are the biochemical markers of organic acidurias?

Answer 5

Metabolic acidosis with high+ anion gap
Raised ammonia (not as high as urea cycle disorders)
Low glucose
Ketones +++

Question 6

What are the biochemical markers of fatty acid oxidation defects?

Answer 6

Metabolic acidosis (not always)
High ammonia
LOW glucose
NO ketones

Question 7

What are the biochemical markers of urea cycle defects?

Answer 7

Metabolic acidosis (sometimes resp alkalosis)
Very high ammonia+++
Normal glucose
Normal ketones

Question 8

When do you use dialysis in sick metabolic kids?

Answer 8

Critically ill with high ammonia/acidaemia

Question 9

When do you give IV arginine?

Answer 9

In urea cycle defects without acidemia

Question 10

When do you give Vit B12

Answer 10

methylmalonic acidemia

Question 11

When do you give biotin?

Answer 11

Multiple carboxylase deficiency

Question 12

Which metabolic disorders give you hypoglycemia?

Answer 12

Disorders of energy metabolism

Disorders of fatty acid oxidation

Question 13

Which metabolic disorders affect Renal function?

Answer 13

Galactosemia
Hereditary fructose intolerance
Wilson's
Tyrosinemia
Cystinosis

Question 14

Which metabolic disorders give you hepatitis?

Answer 14

Galactosemia
Tyrosinemia (type 1)
Fructose intolerance
GsD 4
Wilson's
Storage disorders (Gaucher's, Niemann-Pick)

Question 15

Which metabolic disorders affect the muscle?

Answer 15

GSD 5 (McArdle's)
Carnitine palmitoyl transferase deficiency

Others:
Pompe’s
Fatty acid oxidation derfects
Glycolytic disorders, mitochondrial electron transport chain defects.

Question 16

What metabolic disorders give you hepatomegaly with no neurologic involvement?

Answer 16

Defects in energy metabolism (i.e. GSD_
Peroxisomal disorders
Lysosomal storage disorders (gaucher/nieman pick)

Question 17

What types of metabolic disorders give you cerebral palsy with no hx of perinatal insult?

Answer 17

Arginase deficiency (urea cycle defect)
Fumarase deficiency
Glutaric aciduria type 1

Question 18

Which metabolic conditions give you stroke/thrombosis?

Answer 18

Homocystinuria
Organic acidopathies
MELAS
Protein C/S deficiency

Question 19

What metabolic disorders give you lactic acidosis?

Answer 19

Glucose 6 phosphatase deficiency
Defects in citric acid cycle
Defects in pyruvate metabolism
Defects in mitochondrial electron transport

Question 20

Which metabolic disorders give you proteinuria with no red reflex?

Answer 20

Galactosemia
Wilson disease
Lowe syndome (oculo-cerebral-renal syndrome)

Question 21

What are reducing substances in urine?

Answer 21

glucose, galactose, lactose, fructose, pentose (NOT SUCROSE)

Question 22

What gives you sweaty feet urine?

Answer 22

Isovaleric acidemia

Question 23

What gives you cabbage smell urine?

Answer 23

Tyrosinemia type 1

Question 24

What gives you musty/mousy smell urine?

Answer 24

PKU