metabolic

Question 1

inheritance and cause of phenylketonuria

Answer 1

autosomal recessive

deficiency of phenylalanine hydroxylase -> phenylalanine accumulates

inhibits updatek of tyrosine and trytophan in brain

Question 2

presentation of phenylketonuria

Answer 2

Facial - fair hair, blue eyes, wide spaced teeth, enamel hypoplasia

psychomotor developmental delay , seizures

purposeless hand movements, rhythmic rocking

eczema rash

musty odour

Question 3

diagnosis of phenylketonuria

Answer 3

1. plasma phenylalanine levels >20

Question 4

management of phenylketonuria

Answer 4

1. phenylalanine restricted diet
2. large amino acids e.g. tyrosine, tryphophan

Question 5

inheritance and cause of maple syrup urine disease

Answer 5

autosomal recessive
deficiency of BCKDC leading to accumulation of branced amino acids e.g. luecine, isoleucine and valine

Question 6

presentation of maple syrup urine disease

Answer 6

present in first few days of life with…
- vomiting
- faltering growth
- sweet smelling urine
- poor feeding
- abnormal movements

Question 7

diagnosis of maple syrup urine disease

Answer 7

1. elevated leucine levels (in newborn screening)
2. urine organic acids - increased branched chain keto acids
3. normal gas

Question 8

cause of tyrosinaemia type 1

Answer 8

autosomal recessive

deficiency of FAH leading to accumulation of TYROSINE, methionine and succinylacetone

Question 9

presentation of tyrosinaemia

Answer 9

1. severe liver dysfunction - jaundice, hepatomegaly, cirrhosis, risk of hepatocellular carcinoma
2. cabbage odour
3. faltering growth, developmental delay
4. peripheral neuropathy

Question 10

diagnosis of tyrosinaemia type 1

Answer 10

1. increase succinylacetone (newborn screening)
2. elevated tyrosine and succinylaceteone in urine and serum
3. abnormal LFTs

Question 11

cause of non ketotic hyperglycinaemia

Answer 11

autosomal recessive

mutations in glycine cleavage system causing accumulation of glycine in brain

Question 12

presentation of non ketotic hyperglycinaemia

Answer 12

present few hours of life with…
- myoclonic seizures hiccups
- apnoea
- hypotonia
- encpehalopathy

leads to profound intellectual disability and death

Question 13

diagnosis of non ketotic hyperglycinaemia

Answer 13

1. elevated glycine in blood and CSF
2. genetic mutation GLDC or AMT
3. MRI brain

Question 14

management of non ketotic hyperglycinaemia

Answer 14

1. supportive
2. sodium benzoate - reduces glycine levels
3. dextromethorphan- NMDA antagonist

Question 15

cause of cystinuria

Answer 15

autosomal recessive
defective renal tubular reabsorption of cystine causing build up of cystine and forming stones

Question 16

presentation of cystinuria

Answer 16

• renal stones- flank pain, haematuria
• faltering growth
• urine smells of rotting eggs due to sulphur stones

Question 17

diagnosis of cystinuria

Answer 17

1. urine analysis - cystine crystals
2. amino acid chromatography - increased cystine levels in urine

Question 18

presentation of glutaric aciduria type 1

Answer 18

dystonic movements triggered by minor illness
regression

Question 19

presentation of homocystinuria

Answer 19

stiff joints
learning difficulties
sublexed lens
thrombosis

Question 20

presentation of urea cycle disorders

Answer 20

present as newborn with
- failure to feed
- seizures
- vomiting
- encephalopathy
- tachypnoea

Question 21

diagnosis of urea cycle disorders

Answer 21

1. very high ammonia
2. metabolic acidosis
3. urine for organic acids
4. normal glucose

Question 22

management of acute presentation of urea cycle disorders

Answer 22

1. IV glucose
2. IV sodium benzoate
3. IV sodium phenylbutyrate
4. may need haemodialysis

Question 23

diagnosis of orthinine transcarbamylase

Answer 23

X LINKED RECESSIVE

increased alanine and glutamine
reduced citrilluline and arginine
urine - orotic acid

Question 24

cause of MCADD

Answer 24

mutations in ACAMD gene so inability to breakdown medium chain fatty acids into energy

Question 25

presentation of MCADD

Answer 25

during illness/ prolonged fasting: - hypoketotic hypoglycaemia - metabolic crisises - reduced GCS, lethargy - recurrent infections

Question 26

MCADD diagnosis

Answer 26

1. newborn screening - acylcarnitine (raised C6-C10) 2. genetic testing 3. hypoglycaemia with low ketones 4. raised C8 acylcarnitine levels

Question 27

presentation of refsums disease

Answer 27

anosmia retinitis pigmentosa chronic ataxia neuropathy deafness

Question 28

cause of galactosaemia

Answer 28

autosomal recessive inability to metabolise galactose so accumulation of Gal-1-P and UDP

Question 29

presentation of galactosaemia

Answer 29

- e.coli sepsis as newborn - vomiting - jaundice - faltering growth - oil drop cataractas - developmental delay and seizures

Question 30

diagnosis of galactosaemia

Answer 30

1. increased Gal-1-P levels 2. red cell enzyme levels - reduced GALT 3. increased galcitiol levels in blood and urine

Question 31

cause of hurler syndrome

Answer 31

mucopolysaccharidosis type 1 - inherited lyosomal storage disorder accumulation of glycosaminoglycans

Question 32

presentation of hurler syndrome

Answer 32

- developmental delay in first year of life - coarse facial features - flat nasal bridge widely spaced eyes macroglossia - craniosyntosis - corneal clouding

Question 33

diagnosis of hurler syndrome

Answer 33

1. white cell enzyme activity in leukocytes - L -iduronidase activity 2. genetic testing 3. urine elevated GAG

Question 34

Types of glycogen storage disease

Answer 34

lack of enzyme for glycogen metabolism - pompes - mcardles - von Gierkes

Question 35

presentation of pompes disease

Answer 35

- cardiomyopathy - faltering growth- hypoglycaemia - hypotonia

Question 36

presentation of McArdles disease

Answer 36

pain in muscle during exercise weakness

Question 37

presentation of nieman pick disease

Answer 37

- neurodegeneration - cherry red spot - skin pigmentation

Question 38

diagnsosis of nieman pick

Answer 38

white. cell enzyme assay

Question 39

presentation of cystinosis

Answer 39

- retinitis pigmentosa - hypothyroid - renal tubular acidosis

Question 40

features of von gierkes disease

Answer 40

- doll like face - big cheeks - short - thin extremities - big proturbulent abodmen from hepatomegaly

Question 41

what is von gierkes disease

Answer 41

glycogen storage disorder deficiency of glucose 6 phosphatase plasma = milky appearance due to high triglycerides