metabolic Flashcards
inheritance and cause of phenylketonuria
autosomal recessive
deficiency of phenylalanine hydroxylase -> phenylalanine accumulates
inhibits updatek of tyrosine and trytophan in brain
presentation of phenylketonuria
Facial - fair hair, blue eyes, wide spaced teeth, enamel hypoplasia
psychomotor developmental delay , seizures
purposeless hand movements, rhythmic rocking
eczema rash
musty odour
diagnosis of phenylketonuria
- plasma phenylalanine levels >20
management of phenylketonuria
- phenylalanine restricted diet
- large amino acids e.g. tyrosine, tryphophan
inheritance and cause of maple syrup urine disease
autosomal recessive
deficiency of BCKDC leading to accumulation of branced amino acids e.g. luecine, isoleucine and valine
presentation of maple syrup urine disease
present in first few days of life with…
- vomiting
- faltering growth
- sweet smelling urine
- poor feeding
- abnormal movements
diagnosis of maple syrup urine disease
- elevated leucine levels (in newborn screening)
- urine organic acids - increased branched chain keto acids
- normal gas
cause of tyrosinaemia type 1
autosomal recessive
deficiency of FAH leading to accumulation of TYROSINE, methionine and succinylacetone
presentation of tyrosinaemia
- severe liver dysfunction - jaundice, hepatomegaly, cirrhosis, risk of hepatocellular carcinoma
- cabbage odour
- faltering growth, developmental delay
- peripheral neuropathy
diagnosis of tyrosinaemia type 1
- increase succinylacetone (newborn screening)
- elevated tyrosine and succinylaceteone in urine and serum
- abnormal LFTs
cause of non ketotic hyperglycinaemia
autosomal recessive
mutations in glycine cleavage system causing accumulation of glycine in brain
presentation of non ketotic hyperglycinaemia
present few hours of life with…
- myoclonic seizures hiccups
- apnoea
- hypotonia
- encpehalopathy
leads to profound intellectual disability and death
diagnosis of non ketotic hyperglycinaemia
- elevated glycine in blood and CSF
- genetic mutation GLDC or AMT
- MRI brain
management of non ketotic hyperglycinaemia
- supportive
- sodium benzoate - reduces glycine levels
- dextromethorphan- NMDA antagonist
cause of cystinuria
autosomal recessive
defective renal tubular reabsorption of cystine causing build up of cystine and forming stones
presentation of cystinuria
- renal stones- flank pain, haematuria
- faltering growth
- urine smells of rotting eggs due to sulphur stones
diagnosis of cystinuria
- urine analysis - cystine crystals
- amino acid chromatography - increased cystine levels in urine
presentation of glutaric aciduria type 1
dystonic movements triggered by minor illness
regression
presentation of homocystinuria
stiff joints
learning difficulties
sublexed lens
thrombosis
presentation of urea cycle disorders
present as newborn with
- failure to feed
- seizures
- vomiting
- encephalopathy
- tachypnoea
diagnosis of urea cycle disorders
- very high ammonia
- metabolic acidosis
- urine for organic acids
- normal glucose
management of acute presentation of urea cycle disorders
- IV glucose
- IV sodium benzoate
- IV sodium phenylbutyrate
- may need haemodialysis
diagnosis of orthinine transcarbamylase
X LINKED RECESSIVE
increased alanine and glutamine
reduced citrilluline and arginine
urine - orotic acid
cause of MCADD
mutations in ACAMD gene so inability to breakdown medium chain fatty acids into energy
presentation of MCADD
during illness/ prolonged fasting:
- hypoketotic hypoglycaemia
- metabolic crisises - reduced GCS, lethargy
- recurrent infections
MCADD diagnosis
- newborn screening - acylcarnitine (raised C6-C10)
- genetic testing
- hypoglycaemia with low ketones
- raised C8 acylcarnitine levels
presentation of refsums disease
anosmia
retinitis pigmentosa
chronic ataxia
neuropathy
deafness
cause of galactosaemia
autosomal recessive
inability to metabolise galactose so accumulation of Gal-1-P and UDP
presentation of galactosaemia
- e.coli sepsis as newborn
- vomiting
- jaundice
- faltering growth
- oil drop cataractas
- developmental delay and seizures
diagnosis of galactosaemia
- increased Gal-1-P levels
- red cell enzyme levels - reduced GALT
- increased galcitiol levels in blood and urine
cause of hurler syndrome
mucopolysaccharidosis type 1 - inherited lyosomal storage disorder
accumulation of glycosaminoglycans
presentation of hurler syndrome
- developmental delay in first year of life
- coarse facial features - flat nasal bridge widely spaced eyes macroglossia
- craniosyntosis
- corneal clouding
diagnosis of hurler syndrome
- white cell enzyme activity in leukocytes - L -iduronidase activity
- genetic testing
- urine elevated GAG
Types of glycogen storage disease
lack of enzyme for glycogen metabolism
- pompes
- mcardles
- von Gierkes
presentation of pompes disease
- cardiomyopathy
- faltering growth- hypoglycaemia
- hypotonia
presentation of McArdles disease
pain in muscle during exercise
weakness
presentation of nieman pick disease
- neurodegeneration
- cherry red spot
- skin pigmentation
diagnsosis of nieman pick
white. cell enzyme assay
presentation of cystinosis
- retinitis pigmentosa
- hypothyroid
- renal tubular acidosis
features of von gierkes disease
- doll like face - big cheeks
- short
- thin extremities
- big proturbulent abodmen from hepatomegaly
what is von gierkes disease
glycogen storage disorder
deficiency of glucose 6 phosphatase
plasma = milky appearance due to high triglycerides
