Metabolic disorders

Question 1

PKU

Deficiency?

Answer 1

Phenylalanine hydroxylase

converts phenylalanine to tyrosine

Question 2

PKU

Result?

Answer 2

Phenylalanine builds up in the blood.

Phenylpyruvate and phenylacetic acid result as metabolites
and are excreted in the urine

Question 3

PKU

Symptoms

Answer 3

usually presents by 6 months e.g. with developmental delay

child classically has fair hair and blue eyes

learning difficulties

seizures, typically infantile spasms

eczema

‘musty’ odour to urine and sweat - secondary to phenylacetate, a phenylketone

Question 4

PKU

Dx

Answer 4

Guthrie
blood phenylalanine
phenylpyruvic acid in urine

Question 5

PKU

Tx

Answer 5

take as much phenylalanine out of diet as you can, and institute as early as you can i.e. w/in
first 2 months.

Question 6

Homocystinuria

Answer 6

rare autosomal recessive disease caused by deficiency of cystathionine beta synthase. This results in an accumulation of homocysteine which is then oxidized to homocystine

Question 7

Homocystinuria

Features

Answer 7

often patients have fine, fair hair

musculoskeletal: may be similar to Marfan’s - arachnodactyly etc

neurological patients may have learning difficulties, seizures

ocular: downwards (inferonasal) dislocation of lens

increased risk of arterial and venous thromboembolism

also malar flush, livedo reticularis

Question 8

Homocystinuria

Dx

Answer 8

cyanide-nitroprusside test, which is also positive in cystinuria

Question 9

Homocystinuria

Tx

Answer 9

Treatment is vitamin B6 (pyridoxine) supplements

Question 10

Urea cycle defects

Answer 10

7 enzyme defects of the urea cycle (starts with ammonia urea) – all lead to hyperammonaemia

All AR apart from OTC (X-linked)

Question 11

Urea cycle defects

Red flags

Answer 11

Vomiting without diarrhoea,

respiratory alkalosis/hyperammonaemia,

avoidance/change in diet,

neurological encephalopathy

Question 12

Urea cycle defects

Tx

Answer 12

remove ammonia, reduce ammonia production

Question 13

Organic acidurias

Answer 13

Disrupt BCAA metabolism

Question 14

Organic acidurias

Presentation

Answer 14

neonate, unusual odour, lethargy, feeding problems, truncal hypotonia, limb hypertonia and myoclonic jerks.

Hyperammonaemia with metabolic acidosis and a high anion gap (not from lactate)

Hypocalcaemia, neutropenia, thrombopenia and pancytopenia.

Question 15

Organic acidurias

Chronic intermittent forms of fatty acid oxidation

Answer 15

Recurrent episodes of ketoacidotic coma, cerebral abnormalities

Reyes Syndrome: vomiting, lethargy, increasing confusion, seizures, decerebration, respiratory arrest.

Question 16

Carb disorders - Galactosaemia

Complications

Lab

Answer 16

Unable to break down galactose

3 known disorders of galactose metabolism. Of these galactose-1-phosphate uridyl transferase (gal-1-PUT) is the
most severe and most common.

hepatomegaly, avoid eating, jaundice (conjugated hyperbilirubinaemia), vomiting, diarrhoea,
sepsis e.g. E.Coli

Raised gal-1-phosphate causes liver and kidney disease

urine reducing substrate- pick up galactose, red cell gal-1-PUT

Question 17

Glycogen storage disease type 1

Deficiency?

Consequence

Presentation

Answer 17

11 types. Type 1 is Von Gierke’s disease - glucose-6-phosphate deficiency

Deficiency means gluconeogenetic organs (e.g. liver, muscle & kidney) cant export the glucose that they have
made. Glycogen is then made to stick it somewhere else in the cell

hepatomegaly, nephromegaly, hypoglycaemia, lactic acidosis, convulsions, neutropenia
(neutrophils very dependent on G6P activity)

3/12 months usually, very pretty round little faces.

Question 18

Lysosomal storage disease

Lab

Tx

Answer 18

Intraorganelle substrate accumulation leading to organomegally (connective tissue, solid organs,
cartilage, bone and nervous tissue) with consequences. Dysmorphia- claw like hands, broad face.
Regression of a child. Hydrops.

urine mucoploysaccharides and oligosaccharides. Leucocyte activities.

BMT, exogenous enzymes

Question 19

Lysosomal storage disease

Fabry’s

Answer 19

Genetic cause of dilated cardiomyopathy.

Cherry red spots.

Deficiency of a-galactosidase

Question 20

Peroxismal disorders

Answer 20

Metabolism of very long chain fatty acids and biosynthesis of complex phospholipids

Question 21

Peroxismal disorders

Neonate profile

Answer 21

severe muscle hypotonia, seizures, dysmorphia (lightbulb shaped head),

hepatic dysfunction including mixed hyperbilirubinaemia.

Question 22

Peroxismal disorders

Infant profile

Lab

Answer 22

retinopathy often leading to early blindness, sensorineural deafness,

hepatic dysfunction, mental deficiency, FTT, dysmorphic signs.

Bony changes involve a large fontanel which only closes after the first birthday,

osteopenia of long bones, and often calcified stippling especially the patellar region.

Lab: very long chain fatty acids

Question 23

Mitochondrial disorders

Result

Answer 23

defective ATP production leads to multisystem disease especially affecting organs with a high energy
requirement such as; brain, muscle, kidney, retina and endocrine organs.

Question 24

Mitochondrial disorders

Barth syndrome

Answer 24

cardiomyopathy

neutropenia

Myopathy

Question 25

Mitochondrial disorders

MELAS

Answer 25

mitochondrial encephalopathy

lactic acids

stroke like episodes

Question 26

Mitochondrial disorders

Kearns-Sayre

Answer 26

chronic progressive external opthalamoplegia

retinopathy

deafness

ataxia