T4: New-born Screening Flashcards
What is screening?
Screening is a process of identifying apparently healthy who may be at increased risk of a disease or condition. They can be then offered infirmation, further tests and/or treatment to reduce risk an complications. Screening is never 100% sensitive or specific i.e. false positive and negatives exists.
What is the Wilson and Junger criteria?
This criteria decides which diseases should be screened for. Criteria includes:
- Disease must be sufficiently common - Natural history must be known - Early therapeutic intervention beneficial - Acceptable and affordable screening tests - Diagnostic confirmatory tests
What do we currently screen for in the UK?
- PKU
- Congenital hypothyroidism - not typically inherited
- Sickle cell and Hb disorders
- CF
- MCADD
- MSUD - Maple syrup urine disease
- IVA
- Homocystinuria - non-pyrodixine responsive
- GA1
(Expanded screening)
Occasionally:
- Galactosaemia via PKU pathway) - Tryrosinaemia (via PKU pathway) - GA2 (raised acylcarnitines)
Give details about Phenylketonuria.
• Affects 1: 10,000 Caucasian births
• Caused by a deficiency in phenylalanine hydroxylase
• Severe intellectual disability if untreated
• Excellent prognosis if treated from birth
• Screening test: bloodspot phenylalanine
• Confirm diagnosis with plasma phenylalanine measurements
no need to measure enzyme or DNA
What is the course of untreated PKU?
Natural history of untreated PKU: - Severe intellectual disability - Seizures and tremors - Spasticity - An increased rigidity of muscles due to brain or spinal cord injury. - Behavioural problems and irritability Eczema in childhood
What is the treatment of PKU?
- Low phenylalanine diet - requires careful monitoring but there is the risk of tyrosine insufficiency and vitamin and trace element delicences due to synthetic diet. They would have a low amount of natural phenylalanine.
- The enzyme missing is phenylalanine hydroxylase. Biopterin is the cofactor of this enzyme. A pharmacological dose (saproterinin) of this can be given encouraging the little energy of this enzyme. This may increase slightly the amount of natural protein they can have.
- Large neutral amino acids can be supplemented. Since there is a lot of phenylalanine this can go in the brain preferentially meaning these large amino acids are deficient in the brain. You can supplement these (Val, leu, ileu)
Give details of congenital hypothyroidism.
- Most common affects 1:1500
- Severe prognosis if delayed treatment
- Excellent prognosis if treated from birth
- This is not usually inherited, tends to be sporadic
- Screening test is with bloodspot TSH
- Confirm diagnosis with plasma thyroid function tests - no need to measure enzyme rDNA
- Treatment with thyroxine this has to be carefully monitored though because as the children grow the requirement changes. This is essential for growth and development so monitoring is important.
Give details of MCADD.
- Affects 1:10,000 UK births
- Autosomal recessive inherited defect of fatty acid oxidation
- Body cannot use its own fat reserves to produce energy in periods of fasting or metabolic stress
- Hypoglycaemia and metabolic decompensation develop, which may result in seizures, brain damage or death - Screening test: bloodspot C8 and C8/C10 ratio
Confirmation of diagnosis: - Bloodspot acylcarnitines, urine organic acids, DNA analysis
- Treatment: avoidance of fasting
- Prognosis: good if decompensation avoided. ‘Safe’ times between meals increases as children grow older
What are haemoglonopathies and why are they screened for?
- Early detection and treatment of sickle disease
- Sickle cell disease affects 1:200 babies (can get up to 1 in 300 in places with a higher percentage of ethnic minorities)
- Also detect carriers and compound heterozygotes
- Beta thalassaemia major is detected
- Linked to antenatal haemoglobinopathy screening programme
Sickle cell disease is screened for as 20% of children with undiagnosed SCD may die within the first year due to: - Acute infection - Acute splenic sequestration - Cerebrovascular accident - stroke Screening provides improved outcomes: - Initiate prophylactic penicillin - Parental education
We test for amino acid disorders, fatty acid oxidation defects and organic acidaemia.
There is a variety in what is being tested for across the country and the world.
What is Maple Syrup Urine Disease?
This is the most urgently tested. Classic MSUD presents at 5-10 days of life, they present with encephalopathy, drowsy and floppy and can go into a coma. It can be hard to detect before it has progressed very far. Screening target in leucine. Prevalence is 1:1:116,000.
What is homocystinuria?
Look for methionine. If raised, this is tested for cysteine. Methionine is much easier to measure. Babies usually appear healthy. This is not diagnosed until 2-3 years after birth. If made early on you can present osteoporosis, mental retardation, thromboembolism. Without treatment the patient could die by the age of 30 usually due to thromboembolism.
What is Glutaric Aciduria Type 1?
The metabolic effect is glutaric aciduria 1a deficiency of glutaryl-CoA dehydrogenase. We test for glutaryl carnitine C5DC. 70% present after the neonatal period around 9 months with an encephalopathic crisis. 90% by 2 years. If they become catabolic infection, not eating well, GI illness etc. they can get encephalopathic crisis which can lead to dystonia and dyskinesia as permanent sequelae. They are neurologically intact but have a movement disorder.
What is Isovaleric Acidaemia?
Isovaleric acidaemia is a deficiency in isovalerly-CoA dehydrogenase involved in leucine catabolism. We screen looking for isovaleryl carnitine (C5). This can have a neonatal presentation. Prevalence is 1:155396.
Can have a spectrum of phenotypes:
- Vomiting, lethargy progressing to coma in the acute neonatal stage
- Later age can be precipitated by infection
Chronic intermittent presentations; failure to thrive and/poor developmental delay usually within the first year
