Chempath - metabolic disorders and screening

Question 1

true positive= 90
false positive = 5
true negative = 80
false negative = 10

What is the specificity?

Answer 1

Specificity = the probability that someone without the disease will correctly test -ve

80/85

Question 2

true positive= 90
false positive = 5
true negative = 80
false negative = 10

What is the sensitivity?

Answer 2

Sensitivity = the probability that someone with the disease will correctly test positive

90/100

Question 3

true positive= 90
false positive = 5
true negative = 80
false negative = 10

What is the positive predictive value

Answer 3

PPV = probability that someone with the disease will test +ve

90/95

Question 4

true positive= 90
false positive = 5
true negative = 80
false negative = 10

What is the negative predictive value

Answer 4

NPV = probability that someone without the disease will test -ve

80/90

Question 5

Phenylketonuria - what is it? what are its manifestations? how is it screened for?

Answer 5

Phenylalanine hydroxylase deficiency

Low IQ

measure phenylalanine levels

Question 6

Congenital hypothyroidism - what is the outcome? how is it screened for?

Answer 6

Dysgenesis/agenesis of thyroid gland

Measure TSH levels

Question 7

What level is measured in blood to screen for CF?

Answer 7

Immune reactive trypsin

Question 8

If immune reactive trypsin level is high, what is done next?

Answer 8

DNA mutation detection (4)
If 2 mutations –> CF
If 1 mutation –> repeat with 28
If 0 mutations –> repeat IRT level at 3 weeks of age

Question 9

Level measured in MCADD screening? how?

Answer 9

Acylcarnitine levels by tandem mass spec

Question 10

metabolic acidosis + high anion gap + high ammonia levels + cheesy sweaty smelling urine

Answer 10

Isovolaeric acidaemia

Question 11

Neonates with organic aciduria:

Findings on neuro exam?
Findings on ABG?
Findings on FBC?

Answer 11

Truncal hypotonia + limb hypertonia + myoclonic jerks

Metabolic acidosis + anion gap + high ammonia levels

Pancytopenia

Question 12

Chronic intermittent form of organic acuduria?

Answer 12

Reye syndrome, triggered by aspirin –> Vomiting, lethargy, seizures, confusion, respiratory arrest

Question 13

Eye effects in galactosaemia

Answer 13

Bilateral cataracts

Question 14

2 major presentations of galactosaemia

Answer 14

1) High CONJUG BR

2) SEPSIS

Question 15

Name the mitochondrial disorder that usually presents at 5-15years of age?

Answer 15

MELAS

= mitochondrial encephalopathy, lactic acidosis, stroke-like episodes

Question 16

Hypoketotic hypoglycaemia + hepatomegaly + cardiomyopathy = ?

Answer 16

Mitochondrial fatty acid beta oxidation disorder

Question 17

which lab investigation remains abnormal in remission of Reye syndrome?

Answer 17

Blood post carnitine profile

Question 18

Useful lab investigations in a child who’s taken aspirin and is now lethargic + vomiting + confused + seizing

Answer 18

• Plasma glucose + lactate
• Plasma ammonia
• Plasma amino acids
• Urine organic acids

Question 19

Which organs are particularly affected in mitochondrial disorders?

Answer 19

Brain, heart, kidney, retina

Question 20

the latest presentation of mitochondrial disorder?

Answer 20

Kearns-Sayre syndrome

= ophthalmoplegia, retinopathy, deafness, ataxia

Question 21

CDG type 1a = what type of disorder is this?

Answer 21

defect of post-translational glycosylation

Question 22

wtf is a peroxisomal disorder

Answer 22

Defect in metabolism of v long chain fatty acids + phospholipid synthesis

Question 23

a neonate has severe muscular hypotonia and dysmorphic features (+/-seizures and hepatic dysfunction). What type of metabolic disorder are you worried about?

Answer 23

Peroxisomal disorder

Question 24

What is seen on x-ray of a child with peroxisomal disorder

Answer 24

calcified stippling of the patella

Question 25

why does a child with peroxisomal disorder have a huge head?

Answer 25

Large fontanelle, which only closes at 1 year old

Question 26

Which metabolic disorder leads to organomegaly and why?

Answer 26

Lysosomal storage disease –> substrate accumulation in organelles –> organomegally (CT, solid organs, bone, CNS, cartilage)

This leads to dysmorphia

Question 27

2 Useful investigations for suspected lysosomal storage disorder (organomegaly of erryting)

Answer 27

1. Urine mucopolysaccharides

2. Leukocyte enzyme activity

Question 28

1 useful investigation for a child with suspected perixosomal disorder (severe hypotonia + huge head)

Answer 28

Very long chain fatty acid profile

Question 29

Which lab result is super raised after fasting in mitochondrial disorders?

Answer 29

Lactate

Question 30

How to differentiate between Reye syndrome vs mitochondrial fatty acid b-oxidation disorder?

Answer 30

Blood spot carnitine profile = abnormal in Reye’s

Both present with hypoketotic hypoglycaemia

Question 31

MSUD - inheritance?

Answer 31

Autosomal recessive

Question 32

MSUD is caused by…?

Answer 32

deficiency of branched chain keto-acid dehydrogenase complex

Question 33

Brittle hair
Developmental delay
Convulsions

Answer 33

Homocystinuria

Question 34

Cause of homocystinuria

Answer 34

cystathionine synthetase deficiency

Question 35

PKU - appearance and smell of child?

Answer 35

Fair child

Musty smell

Question 36

Name an eponymous syndrome which is a glycogen storage disease

Answer 36

Von Gierke’s

Question 37

Fabry’s disease - what kind of disorder is it? how does it present (3 Fx)?

Answer 37

Lysosomal storage disease

LDs + dysmorphia + cherry red spot

Question 38

Cherry red spot

Answer 38

Lysosomal storage disease eg Fabry’s

Question 39

V v sweaty feet

Answer 39

Maple syrup urine disease