Chem path - metabolid disorders and screening Flashcards
Briefly explain Wilson and Junger criteria
In short:
Needs to be able to solve a medical problem cost effectively in a well thought out manner that can be implemented in a practical way.
Child child presents with seizures and hypopigmentation. Skin smells ‘musty’ and head looks small for age. Baby wasn’t heel prick tested at birth.
Phenylketouria
Body lacks enzyme phenylalanine hydroxylase, so is unable to hydroxylase the amino acid phenylalanine into tyrokine, leading to a build up.
When broken down, releases toxic metabolites:
Phenylpyruvate
Phenylacetic acid, which is excreted in urine. (hence ketouria)
Needs to be on Phe/protein restricted diet, with protein substitutes (non phe of course) to cover deficiencies.
What are the consequences of untreated phenylketouria?
Severe LD - IQ<50
Also causes hyperactivity, seizures, mood and behavioural issues.
Irreversible damage if untreated as a child. If managed well as a child, can live on to a perfectly normal and healthy life.
1/10000 incidence, easy to test (check blood phenylalanine levels) and very easily treatable - hence why very appropriate for screening
What is a Gutrie test?
Neonatal heel prick test. Involves pricking a neonate and gushing its blood over a ‘gutrie card’, which has magical bacteria that can tell you if you got an inborn error of metabolism.
Requires a specialist newborn screening lab
Phenylketouria positive predictive value?
~80% for classical PKU - the autosomal recessive deficiency in phenylalanine hydroxylase
What do they look for in congenital hypothyroidism?
TSH, PPV of ~60-70% - reason for low PPV is a low TSH may be transient - due to maternal Abs.
Common! 1 in 4000 have severe deficiencies whilst many more have mild/moderate.
Nothing remarkable to present - might have excessive sleeping, jaundice, low and hoarse cry and reduced interest, but will mostly go unnoticed.
If left untreated, will result in permanent learning disability and growth stunt.
Caused by iodine deficiency (most common cause worldwide) as well as genetic or anatomical.
A completely absent thyroid will present with large anterior fontanelle, a persistent posterior fontanelle, a large tongue and umbilical hernia
What do they test for in Cystic Fibrosis?
High immune reactive trypsin test
Immune reactive trypsinogen (IRT) is a pancreatic enzyme precursor found in the blood that is raised in most of those with CF at birth, regardless of whether their mutation is pancreatic sufficient or insufficient. The concentration of IRT is elevated in babies with CF since pancreatic ducts are partially blocked leading to abnormal enzyme drainage.
1:2500 - again very common
Added after evidence showed early intervention showed best outcomes. If test is positive -> DNA mutation detection
Which inborn error of metabolism that is routinely screened is a defect in Beta oxidation?
MCADD (Medium Chain Acyl CoA Dehydrogenase)
Cannot make Acetyl CoA with beta oxidation - so fat metabolism is inhibited. This means cannot make ketone bodies and glucose cannot be spared as easily. Therefore, if there is a hypo - death. Generally will present quite late
Cause of cot death - hypoketotic hypoglycaemia. Screen by detecting C6-C10 AcylCarnitines by tandem mass spec. Acylcarnitines build up due to pathway block.
May present similarly to phenylketonuria but not as severe?
Homocystinuria
Defect in metabolism of methiaonine (start codon) by enzyme cystathionine beta synthase. Leads to a buildup of homocysteine in blood and urine.
Can present similarly to PKU but is not as severe. More likely, it will cause connective tissue and muscle problems.
a. Lens dislocation
b. Mental retardation
c. Thromboembolism
Same diet restrictions apply as PKU
