Metabolic Disorders

Question 1

Describe primary lactase deficiency
-What is it?
-Highest prevalence
-Who does it occur in?

Answer 1

-It is the absence of lactase persistence allele
-Highest prevalence in Northwest Europe
-Only occurs in adults

Question 2

Describe secondary lactase deficiency
-What is it caused by? (with examples)
-Who does it occur in?
-Is it reversible?

Answer 2

-Caused by injury to the small intestine: e.g. Gastroenteritis, Coeliac disease, Crohn’s disease, Ulcerative Colitis.
-Occurs in both adults and infants
-Generally reversible

Question 3

Describe congenital lactase deficiency
-Rarity
-Mode of inheritance
-What can’t be digested?

Answer 3

-Extremely rare
-Autosomal recessive defect in lactase gene
-Cannot digest breast milk

Question 4

Galactosaemia
-What is it?
-Symptoms
-Enzymes deficiency
-Problems
-Treatment

Answer 4

-Unable to utilise glucose

Enzymes deficiency:
-Galactokinase deficiency: galactose accumulates
-Transferase deficiency: galactose and G1P accumulate

Symptoms:
-Hepatosplenomegaly + Cirrhosis
-Renal failure
-Swelling
-Cataracts
-Hypoglycaemia

Problem:
-Galactose enters other pathways
-Depletes lens of NADPH -> structure damage -> cataracts
-Accumulation of G1P affects liver, kidney and brain

Treatment:
-No lactose in diet

Question 5

Describe essential fructosuria
-What’s missing?
-How is it detected?

Answer 5

-When fructokinase is missing
-Fructose is present in the urine

Question 6

Fructose intolerance
-What’s missing?
-What accumulates and its consequences
-Management

Answer 6

-Aldolase is missing
-Fructose 1-P accumulates in liver -> leads to liver damage and possible death
-Managed by removing fructose and sucrose from the diet

Question 7

G6PDH Deficiency
-What does decreased G6PDH activity lead to?
-Presentation
-Clinical sign
-Treatment

Answer 7

-Decreased G6PDH deficiency activity limits the amount of NADPH. Lower GSH means less protection against damage from oxidative stress.

Presentation:
-Splenomegaly
-Jaundice
-Fatigue
-Pallor

Clinical sign:
-Heinz bodies present

Treatment:
-Treat oxidative stress (stop primaquine)

Question 8

Describe Phenylketonuria (PKU)
-What is it?
-Mode of inheritance
-What accumulates?
-Presentation
-Treatment

Answer 8

What is it?
-Deficicency in phenylalanine hydroxylase

Mode of inheritance
-Autosomal recessive

What accumulates?
-Accumulation of phenylalanine in tissue, plasma and urine

Presentation:
-Phenylketones in urine
-Musty smell

Treatment:
-Strictly controlled low phenylalanine diet with enriched tyrosine
-Avoid artificial sweeteners
-Avoid high protein foods such as meat, milk and eggs

Question 9

Symptoms of PKU

Answer 9

Seizures
Hypopigmentation
Microcephaly (small head)

Question 10

Describe homocystinurias
-What is it?
-Mode of inheritance
-What does it affect?
-Treatment

Answer 10

What is it?
-A problem breaking down methionine

Mode of inheritance:
-Autosomal recessive disorders

What does it affect?
-Affects connective tissue, muscles, CNS, CVS

Treatment:
-Low methionine diet
-Avoid milk, fish, meat, cheese, eggs, nuts
-Cysteine, B12 and folate supplement

Question 11

Examples of glycogen storage diseases and what they are.

Answer 11

-von Gierke’s disease: glucose 6-phosphatase deficiency
-McArdle disease: muscle glycogen phosphorylase deficiency

Question 12

Hypercholesterolaemia
-What is it?
-Clinical signs

Answer 12

-High level of cholesterol in blood

Clinical signs:
-Xanthelasma (yellow patches on eyelids)
-Tendon Xanthoma (nodule on tendon)
-Corneal arcus (obvious white/blueish circle around eye)

Question 13

Treatment of hyperlipoproteinaemias
-First approach
-Drugs

Answer 13

First approach:
-Diet: reduce cholesterol and saturated lipids in diet. Increase fibre intake
-Lifestyle: increase exercise, stop smoking to reduce CVS risk

Drugs:
-Statins: reduce cholesterol synthesis by inhibiting HMG-CoA reductase e.g. Atorvastatin
-Bile salt sequestrants: forces liver to produce more bile acids, therefore using more cholesterol