Chempath 6: Metabolic disorders and screening 2 Flashcards
A neonate presents with cataracts, conjugated bilirubinaemia, hepatomegaly after starting milk feeds.
Most likely metabolic disease ?
Galactosaemia
A positive Fehling’s and Benedict’s test in the absence of glucose in the urine suggests …………….
Glacatosaemia
These tests detect reducing sugars in the urine.
A baby born in Quebec Canada presents with bloody stool, failure to thrive, jaundice, hepatomegaly and a cabbage like odour.
What is the most likely diagnosis ?
Tyrosinaemia (type 1)
treated by restricting tyramine in the diet (soft cheese etc)
A neonate presents with signs of a non-infective encephalopathy, failure to thrive and hyperventilation. The consultant suggests that Protein may be the trigger.
Most likely diagnosis ?
Urea cycle disorders
list disorders that count as urea cycle defects
lysinuric protein intolerance
hyperornithaemia - hyperammonemia - homocitrullinuria
citrullinaemia type II
all result in a high ammonia
all autosomal recessive
high plasma glutamine
how do you treat ornithine cycle disorders
remove ammonia (using sodium benzoate or sodium phenyl acetate) reduce ammonia production (by low protein diet)
list key features of urea cycle disorders
vomiting without diarrhoea respiratory alkalosis hyperammonaemia neurological encephalopathy avoidance or change in diet
causes of hyperammonaemia with metabolic acidosis and a high anion gap
organic acidurias
caused by defects within the metabolism of branched chain AA
associated with funny smelling urine (cheesy/ sweaty smell)
presentation of organic acidurias in neonates
unusual odour lethargy feeding problems truncal hypotonia/ limb hypertonia myoclonic jerks hyperammonaemia with metabolic acidosis and high anion gap
presentation of chronic intermittent organic acidurias
recurrent episodes of ketosis coma
cerebral abnormalities
Reye syndrome: plasma ammonia, plasma/urine AA, urine organic acids, plasma glucose and lactate
list features of mitochondrial fatty acid beta oxidation disorders
cause hypoketotic hypoglycaemia
hepatomegaly and cardiomegaly
investigations = blood ketones, urine organic acids, blood spot acylcarnitine profile
features of carbohydrate disorders
cannot break down carbs
galactosaemia
glactose-1-phosphate uridyl transferase (Gal-1-PUT) deficiency is most severe and common form
leads to liver and kidney disease
presentation of carbohydrate disorders
vomiting diarrhoea conjugates hyperbilirubinaemia hepatomegaly hypoglycaemia sepsis bilateral cataracts
inv: urine reducing substances (high galactose levels), red cell Gal-1-PUT
tx - avoid galactose
features of glycogen storage disease type 1 (von Gierke disease)
phosphatase deficiency
cannot export G6P and G1P after glucose breakdown
become hypoglycaemic
features: hepatomegaly, nephromegaly, hypoglycaemia, lactic acidosis, neutropenia
features of mitochondrial disorders
maternally inherited
defective ATP production - multisystem disease esp affecting organs with high energy requirements
investigations in mitochondrial disorders
high lactate
CSF lactate/pyruvate
CK
muscle biopsy
features of congenital disorders of glycosylation
defect of post-translational protein glycosylation
associated with cardiomyopathy, osteopenia, hepatomegaly, sometimes dysmorphic facial features
features of paroxysmal disorders
metabolism of long chain fatty acids and biosynthesis of complex phospholipids
neonates: muscular hypotonia, seizures, hepatic dysfunction, mental deficiency
infantile: bony changes
features of lysosomal storage disorders
defects of lysosomal hydrolyses
accumulation of substrates within organelles - organomegaly
dysmorphia, regression
treat: BM transplant, exogenous enzymes
describe what’s been included in the Guthrie screening
1969 - PKU 1970 - congenital hypothyroidism 2004 - CF 2006 - SCD 2009 - medium chain acylcoa dehydrogenase deficiency
2 key features of PKU
phenylalanine hydroxylase deficiency
test phenylalanine levels
2 key features of congenital hypothyroidism
dysgenesis/agenesis of thyroid gland
test TSH levels
2 key features of CF
mutations of CFTR - viscous secretions - ductal blockages
test: immune reactive trypsin
if positive - DNA mutation detection
2 key features of medium chain acylcoa dehydrogenase deficiency
fatty acid oxidation disorder
acylcarnitine levels by tandem mass spectrometry
define specificity
probability in % that someone without the disease will correctly test negative
define sensitivity
probability in % that someone with the disease will test correctly positive
define PPV
probability that someone who tests positive actually has the disease
define NPV
probability that someone who tests negative actually doesn’t have the disease
list group 1 metabolic disorders
accumulation of toxins…
organic acidameias - high urea, ketones, met acidosis, treat with low protein diet, acetylcarnitise and harm-filtration, funny smells
urea cycle disorders - high ammonia, respiratory alkalosis, vomiting, treat with low protein diet
aminoacidopathies inc PKU - high phenylalanine, blue eyes, retardation
list group 2 metabolic disorders
reduced energy stores…
glycogen storage disorders - hypoglycaemia, lactic acidosis, hepatomegaly, developmental delay, hepatoblastoma, treat with regular CHO
galactossaemia - increased Gal-1-phosphate levels causing cataracts, hypoglycaemia, neonatal conjugated jaundice, test urine, treat with low lactose/galactose diet
fatty acid oxidation disorders - hypoglycaemia, neonatal conjugated jaundice, low ketones, screen with blood acylcarnitine, test iron organic acids, regular carbs
list group 3 metabolic disorders…
large molecule synthesis…
peroxisomal disorders - poor feeds, seizures, retinopathy, hepatomegaly, mixed hyperbilirubinaemia
glycosylation disorders - measure serum transferring, lead to retardation and nipple retraction
list group 4 metabolic disorders…
defects in large molecule metabolism…
lysosomal disorders - slow progressing, neuroregression, hepatosplenomegaly, cardiomyopathy, test urine mucopolysaccharides and WBC enzyme levels
list group 5 metabolic disorders…
mitochondrial
MELAS, Kearns, Sayre POEMS
involve CNS, muscle, heart, high lactate and CK, muscle biopsy diagnostic
