33 - Neonatal screening

What is the concept of screening?

Process of identifying apparantly healthy people who may be at risk of a disease

What is the Wilson and Junger Criteria?

A criteria that should be applied before implementing a potential population screening programme

What are the 5 terms included in the Wilson and Jungner Criteria?

1) Disease must be common

2) Natural history must be known

3) Early therapeutic intervention beneficial

4) Acceptable and affordable screening test

5) Diagnostic confirmatory test

On what day are all newborn babies screened?

Day 5

What is another term used to describe the neonatal screening test?

Heel prick test

What is the process of neonatal screening (heel prick test)?

1) Blood sample is taken and placed on a new-born spot card

2) 3mm discs are punched from spots and placed in a machine

3) Discs are placed in a tandem mass spectrometry machine

How many rare health conditions are screened for in the UK neonatal test?

9

What are the 9 rare health conditions screened for in the neonatal screening test?

1) Congenital hypothyroidism

2) Sickle cell and Hb disorders

3) CF (cystic fibrosis)

4) PKU (phenylketonuria)

5) MCADD (medium chain acyl CoA dehydrogenase deficiency)

6) MSUD (maple syrup urine disease)

7) IVA (isovaleric acidaemia)

8) Homocystinuria - non-pyridoxine responsive

9) GA1 (glutaric aciduria type 1)

What rare health condition is currently being piloted for neonatal screening in the UK?

SCID

What is phenylketonuria (PKU)?

Amino acid phenylaline is unable to be broken down causing accumulation and so neurological damage and lack of skin colouration

What amino acid accumulates in PKU?

Phenylalanine

What are some clinical signs of phenylketonuria (PKU)?

- Severe intellectual disability

- Seizures

- Spasticity

- Behavioural problems

- Eczema in childhood

What is the treatment for phenylketonuria (PKU)?

- Low phenylalanine diet

- Biopterin/sapropterin supplementation

What are 2 deficiencies associated with phenylketonuria (PKU)?

1) Tyrosine deficiency

2) Vitamins and trace element deficiency

How does biopterin treat phenylketonuria?

It is a cofactor in the enzyme breakdown of phenylalanine

What causes congenital hypothyroidism?

Thyroid dysgenesis or agenesis

What molecule is screened for in congenital hypothyroidism testing?

TSH

How is congenital hypothyroidism treated?

Thyroxine

What is the pattern of inheritance of medium chain acyl CoA dehydrogenase deficiency?

Autosomal recessive

What causes medium chain acyl CoA dehydrogenase deficiency?

An inherited defect of fatty acid oxidation meaning the body cannot use its own fat reserves to produce energy in periods of fasting and metabolic stress

What are 2 physiological signs associated with medium chain acyl CoA dehydrogenase deficiency?

1) Hypoglycaemia

2) Metabolic compensation

What are 3 presentations of MCADD?

1) Seizures

2) Brain damage

3) Death

What molecules are tested for in neonatal MCADD screening?

1) C8

2) C8/ C10 ratio

What test diagnoses MCADD following positive screening?

Blood spot acyl carnitine test

How is MCADD treated?

Fasting avoidance

What molecule is tested for in CF neonatal screening?

IRT

What is used to diagnose CF after a positive screening test?

DNA analysis

What are 3 treatments for CF?

1) Ivacaftor

2) Elexacaftor

3) Tezacaftor

What are 2 common haemoglobinopathies?

1) Sickle cell

2) Beta-thalassaemia

What does tandem mass spectrometry detect?

- Amino acid disorders

- Fatty acid oxidation defects

- Organic acidaemias

What is Maple Syrup Urine Disease (MSUD)?

A defect in branched chain 2-keto acid dehydrogenase complex and so an accumulation of leucine, valine, isovaline

What are 5 presentations of untreated MCUD?

1) Encephalopathy

2) Cerebral oedema

3) Poor feeding

4) Ketoacidosis

5) Seizures

What molecules is screened for in MCUD?

Leucine

What causes homocystinuria?

Impaired cystathionine beta-synthase activity resulting in elevated homocysteine and methionine in plasma/urine

What are the 2 types of homocystinuria?

1) Pyridoxine (vit B6) responsive

2) Pyridoxine unresponsive

Give 5 presentations of untreated homocystinuria?

1) Myopia followed by dislocation of the lens

2) Osteoporosis

3) Thinning and lengthening of the long bones

4) Mental retardation

5) Thromboembolism

What molecule is screened for in homocystinuria?

Methionine

What causes glutaric aciduria Type 1?

A deficiency of glutaryl-CoA dehydrogenase used in lysine breakdown causing lysine accumulation

Give 6 presentations of untreated glutaric aciduria Type 1?

1) Non-specific intercurrent illness

2) Encephalopathic crisis

3) Gastrointestinal infection

4) Pneumonia

5) Dystonia

6) Dyskinesia

What is dystonia?

Involuntary sustained muscle contractions, producing twisting or squeezing movement and abnormal postures

What is dyskinesia?

Difficulty performing voluntary movements

What molecule is screened for in glutaric aciduria Type 1?

Glutaryl carnitine (C5DC)

What causes isovaleric acidaemia?

A deficiency of isovaleryl-CoA dehydrogenase involved in leucine catabolism

Give 4 presentations of untreated isovaleric acidaemia?

1) Vomiting

2) Lethargy

3) Coma

4) Infection

What molecule is screened for in isovaleric acidaemia?

Isovaleryl carnitine (C5)

What are clinical signs of SCID?

- Poor feeding

- Chronic diarrhoea

- Failure to gain weight

What is the treatment for SCID?

- HSCT (haematopoietic stem cell transplantation?

- Gene therapy

What causes tyrosinaemia Type 1?

Defect in FAH (fumarylacetoacetate hydrolyse) gene

What are 6 clinical features of untreated tyrosinaemia Type 1?

1) Fever

2) Diarrhoea

3) Vomiting

4) Hepatomegaly

5) Clotting disturbances

6) Jaundice

What molecule is screened for in tyrosinaemia Type 1?

succinylacetone

What are the treatments for tyrosinaemia Type 1?

- Nitisinone

- Low tyrosine diet