Metabolic disorders Flashcards
PKU
Deficiency?
Phenylalanine hydroxylase
converts phenylalanine to tyrosine
PKU
Result?
Phenylalanine builds up in the blood.
Phenylpyruvate and phenylacetic acid result as metabolites
and are excreted in the urine
PKU
Symptoms
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
PKU
Dx
Guthrie
blood phenylalanine
phenylpyruvic acid in urine
PKU
Tx
take as much phenylalanine out of diet as you can, and institute as early as you can i.e. w/in
first 2 months.
Homocystinuria
rare autosomal recessive disease caused by deficiency of cystathionine beta synthase. This results in an accumulation of homocysteine which is then oxidized to homocystine
Homocystinuria
Features
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
Homocystinuria
Dx
cyanide-nitroprusside test, which is also positive in cystinuria
Homocystinuria
Tx
Treatment is vitamin B6 (pyridoxine) supplements
Urea cycle defects
7 enzyme defects of the urea cycle (starts with ammonia urea) – all lead to hyperammonaemia
All AR apart from OTC (X-linked)
Urea cycle defects
Red flags
Vomiting without diarrhoea,
respiratory alkalosis/hyperammonaemia,
avoidance/change in diet,
neurological encephalopathy
Urea cycle defects
Tx
remove ammonia, reduce ammonia production
Organic acidurias
Disrupt BCAA metabolism
Organic acidurias
Presentation
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.
Organic acidurias
Chronic intermittent forms of fatty acid oxidation
Recurrent episodes of ketoacidotic coma, cerebral abnormalities
Reyes Syndrome: vomiting, lethargy, increasing confusion, seizures, decerebration, respiratory arrest.
Carb disorders - Galactosaemia
Complications
Lab
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
Glycogen storage disease type 1
Deficiency?
Consequence
Presentation
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.
Lysosomal storage disease
Lab
Tx
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
Lysosomal storage disease
Fabry’s
Genetic cause of dilated cardiomyopathy.
Cherry red spots.
Deficiency of a-galactosidase
Peroxismal disorders
Metabolism of very long chain fatty acids and biosynthesis of complex phospholipids
Peroxismal disorders
Neonate profile
severe muscle hypotonia, seizures, dysmorphia (lightbulb shaped head),
hepatic dysfunction including mixed hyperbilirubinaemia.
Peroxismal disorders
Infant profile
Lab
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
Mitochondrial disorders
Result
defective ATP production leads to multisystem disease especially affecting organs with a high energy
requirement such as; brain, muscle, kidney, retina and endocrine organs.
Mitochondrial disorders
Barth syndrome
cardiomyopathy
neutropenia
Myopathy
Mitochondrial disorders
MELAS
mitochondrial encephalopathy
lactic acids
stroke like episodes
Mitochondrial disorders
Kearns-Sayre
chronic progressive external opthalamoplegia
retinopathy
deafness
ataxia
