Metabolics

Question 1

A child has seizures, intellectual disability, fair skin and hair, movement disorder, spasticity. They also have mousy odour urine. What is the likely classical metabolic disorder and what investigation would you do to identify the diagnosis?

Answer 1

Phenylketonuria

• Phenylalanine is toxic to brain and sx occur over time (NOT an acute presentation)
• Most Dx on NMS now!
• Invx: plasma amino acids: increased phenylalanine, urine organic acids, gene testing
• Tx: restriction of phenylalanine in the diet, supplementation with medical formula

Question 2

A child has a history of recurrent thrombosis, and intellectual disability. They also have a history of ectopia lentis. On exam you notice tall stature/marfanoid body habitus. What is the most likely diagnosis? What investigations would you do to identify the diagnosis?

Answer 2

Homocysteinuria

• Note differences to Marfan’s inc. downward lens displacement and intellectual disability
• Invx: pAA (increased methioniene and homocystein), uOA, genetics
• Tx: Methionine restriction, aspirin, B6

Question 3

A child presents with acute liver failure and has a type II RTA. What metabolic disorder is at the top of your differential?

Answer 3

Tyrosinemia I

• Hepatic dysfunction, can progress to cirrhosis; FTT, porphyric crises, renal fanconi
• Invx: pAA (increased tyrosine), uOA (succinylacetone - pathognomonic)
• Tx: phenylalanine and tyrosine restriction, may need liver transplantation

Question 4

You are following a child in your general pediatrics clinic with Tyrosinemia I. What screening lab for malignancy would you do?

Answer 4

AFP

-Like all metabolic hepatopathies, can progress to hepatocellular carcinoma

Question 5

A child presents with subdural hemorrhage. What metabolic disorder is on your differential?

Answer 5

Glutaric Aciduria Type I

• Macrocephaly (MRI: benign extraaxial hydrocephalus and benign frontotemporal atrophy), acute metabolic basal ganglia stroke w/ fever, spont. subdural hemorrhages
• Invx: uOAs (inc. glutaric acid), free and total carnitine (dec), acylcarnitine profile, genetics

Question 6

What type of metabolic d/o presents with hyperammonemia and respiratory alkalosis?

Answer 6

Urea cycle defects

• Most common d/o = Ornithine Transcarbamylase Deficiency (OTC)
• Note: organic acid d/o often have severe metabolic acidosis (in contrast to resp. alkalosis)

Question 7

What is the pathognomonic, finding on uOA for tyrosinemia?

Answer 7

Succinylacetone

Question 8

What type of metabolic d/o presents with hyperammonemia and metabolic acidosis?

Answer 8

Organic acid disorders

-Metabolic acidosis, hyperammonemia, elevated ketones and lactate

Question 9

Which metabolic d/o which can be identified on newborn screening can be a result of a false positive related to G6PD?

Answer 9

Galactosemia

-GALT enzyme activity (false positive in G6PD)

Question 10

Which metabolic disease results in cherry red spots on the fundus?

Answer 10

Tay Sachs

Gaucher also had cherry red spots

Question 11

What group of metabolic disorders should you think of when you see the following:
Hypoglycemia (Ketotic)
Lactic acidosis
HyperTGs
Hyperuricemia
Hepatomegaly

Answer 11

Glycogen Storage Disorders