What is it?
This is a metabolic genetic disorder affecting the metabolism of the amino acid, phenylalanine.The disorder results in phenylalanine accumulating in the blood and brain. If left untreated this can damage the brain and nervous system causing learning disabilities, behavioural difficulties and seizures.
What causes it?
It is an autosomal recessive condition where the liver enzyme phenylalanine hydroxylase cannot metabolize phenylalanine to tyrosine effectively.
Are there any risk factors?
It is an autosomal recessive disorder. This means to inherit the condition both parents must have at least one of a pair of alleles with the mutated gene controlling phenylalanine hydroxylase. The child must inherit both mutated alleles, one from each parent, to develop the condition.
What is the pattern in Wales and the world?
The prevalence in Wales is 0.96 per 10,000 live births, as recorded by CARIS. This compares with an estimated prevalence of 1 per 10,000 live births in Europe by Orphanet. Orphanet is a register of rare conditions and records a higher prevalence of PKU in Ireland and Italy, and especially Turkey, but lower prevelance in Finnish, African and Japanese populations.
What about detection?
PKU is usually diagnosed at the newborn bloodspot screen. This uses a small sample of blood taken from the baby’s heel on day 5 to day 8 of life. Parents of children known to have PKU may be offered an earlier bloodspot screening test specific for PKU, one to two days after birth. There is no antenatal detection.
Numbers reported to CARIS
On average about three cases per year are reported to CARIS.
What is the management and outcome?
If PKU is diagnosed early, an affected baby can grow up with normal brain development by managing and controlling phenylalanine levels primarily through diet combined with amino acid supplementation. This includes avoiding many protein sources and dairy products. When left untreated, complications include severe learning difficulties, brain function abnormalities, microcephaly, mood disorders, irregular motor functioning, and behavioural problems. There is some evidence that adults with PKU that have been treated may be more likely to develop mental health problems such as depression or anxiety [Source: NHS Direct/NHS Choices].
Mothers with PKU
High levels of phenylalanine which cross the placenta can affect the developing fetus in terms of congenital heart disease, growth restriction, microcephaly and learning difficulties. It is essential that maternal phenylalanine levels are carefully controlled. Mothers with PKU are not at risk of additional complications during pregnancy.
Further information:
What is it?
This is a rare inherited disorder where the body cannot metabolise fat properly. It can present as an encephalopathy, usually with hypoglycaemia, resulting in coma or death.
What causes it?
The enzyme Medium Chain Acyl-CoA Dehydrogenase is responsible for the dehydrogenation step of fatty acids as they undergo beta-oxidation in the mitochondria. This provides energy after the body has used up its stores of glucose and glycogen e.g. illness or fasting. If the enzyme is deficient this pathway cannot work to create an additional energy supply.
What are the risk factors?
The deficiency gene is inherited as an autosomal recessive. This means that an affected individual must inherit a mutated allele from both of their parents. Most cases of MCADD are related to a prevalent point mutation (985A>G).
What is the pattern in Wales and the world?
Expected prevalence has been put at 0.94 per 10,000 (Oerton J et al 2011). Only 4 cases have been reported to CARIS (1998-2012) and this would equate to a prevalence of 0.08 per 10,000. However, as MCADD has been added to newborn bloodspot screening in Wales from June 2012, the prevalence recorded by CARIS may change over time.
What about detection?
Newborn bloodspot screening commenced in Wales in June 2012. If there is a known family history of MCADD then earlier blooodspot screening may be offered one to two days after birth specifically for MCADD. There is no antenatal detection.
What is the management and outcome?
The introduction of screening should improve the outcome for those diagnosed and result in more families being aware they could be carriers of MCADD.
Those diagnosed with MCADD need to avoid fasting for prolonged periods of time and careful management of any illness. Management of illness may include frequent regular feeds, or drinks of glucose polymer; if this is not tolerated, emergency intravenous treatment may be needed.
Adults with MCADD need to also be aware of and safely manage risks of heavy alcohol intake and particular approaches to weight management.
Further information:
What is it?
The baby is born with a thyroid gland which is not functioning normally. This results in low thyroxine levels. Some babies are born with jaundice, dry skin, puffy eyelids, larger tongue, hoarse cry, feeding problems, constipation and sleepiness. Without thyroxine the baby will not develop properly, mentally or physically.
What causes it?
Iodine deficiency is the most common cause in the developing world, but in the west, defective development of the thyroid gland is often responsible, whose causes are unknown. There are rare genetic defects affecting the synthesis of thyroxine.
It can also be caused by congenital hypopituitarism.
Any risk factors?
A maternal diet poor in iodine is the main known risk factor. Mothers with autoimmune thyroid disease, taking antithyroid drugs or exposed to high doses of iodine can result in transient congenital hypothyroidism.
Prevalence
The live birth prevalence in Wales is 6.6 per 10,000 (CARIS 1998-2016). Orphanet (rare conditions register) give an estimate of 1 to 5 per 10,000.
What about detection?
Congenital hypothyroidism is diagnosed on the newborn bloodspot screening programme.
What about management and outcome?
Babies diagnosed with congenital hypothyroidism are treated with thyroxine and usually develop normally.
Further information:
What is it?
Cystic fibrosis (CF) is a genetic disorder where sweat with a high salt content and mucus secretions with an abnormal viscosity are produced.
What causes it?
Cystic fibrosis is caused by a mutation in the CFTR gene (chromosome 7). This allows too much salt and water into cells, causing a build-up of sticky mucus in the body’s tubes and passages. These in turn can damage the lungs, digestive system and other organs.
Any risk factors?
Cystic fibrosis is an autosomal recessive condition. This means that an affected individual must inherit a mutated allele from both parents.
What is the pattern in Wales and the World?
It is considerably less common in Asian and African populations than in the white populations of Europe and North America. The Welsh prevalence is 4.34 per 10,000 live births (CARIS, 1998-2012). This means that about 1:2,300 live births are affected in Wales. The World Health Organisation estimate that between 1 in 2,000-3,000 live births are found to be affected by CF in the European Union and about 1:3,500 live births in the United States.
What is the management and outcome?
Antenally, it may present with echogenic bowel identified on ultrasound. Meconium ileus may present at birth. Respiratory, pancreatic (diabetes) and digestive complications reflect the difficulties with mucus secretions. Male infertility is common. Treatment includes high-energy diet, medicines and physiotherapy. Mortality and morbidity depend on the extent of bronchopulmonary involvement but has greatly improved in recent years. Of the 135 babies born with CF between 1998 and 2006 on the CARIS register, 98% survived to their fifth birthday.
What about detection?
Antenatal diagnosis is possible using chorionic villus sampling or amniotic fluid from amniocentesis.
Newborn bloodspot screening for cystic fibrosis detects the majority of cases. Later diagnosis is based on sweat tests and confirmation of the gene mutation.
Further information:
What is it?
Congenital adrenal hyperplasia (CAH) is an inherited endocrine disorder caused by an enzyme deficiency in steroid production that causes adrenal insufficiency.
The most frequent form is due to 21-hydoxylase deficiency. Girls present at birth with ambiguous genitalia and variable levels of virilization. They have a normal uterus but abnormal vaginal development. The external genitalia in boys are normal. Salt wasting forms of CAH lead to symptoms of dehydration and hypotension in the first few weeks of life and can be life threatening.
What causes it?
In most cases, CAH is caused by a mutation in the CYP21A2 gene located on chromosome 6p21.3. This affects cortisol and aldosterone production.
Any risk factors?
CAH is an autosomal recessive disorder and genetic counseling can be offered to parents with CAH. Dexamethasone can be given to pregnant women at risk of having offspring with the mutation (when fetus is female) in order to prevent virilization in girls.
What is the pattern in Wales and the world?
The prevalence rate in Wales is 0.84 per 10,000 live births. (1:11,900 live births). Estimates by Ophanet give a range of 1:5,000 to 1:15,000 live births
What about detection?
Antenatal diagnosis is possible by screening for the gene by amniocentesis or chorionic villus sampling if the condition is suspected.
Diagnosis of girls with classical CAH is usually at birth when ambiguous genitalia are present. Babies can be screened for CAH in order to identify those with the classical forms by measuring 17-hydroxy-progesterone (17-OHP) levels. Genetic screening at birth can also confirm a diagnosis but this is not done in Wales.
What is the management and outcome?
Lifelong hormone replacement therapy is needed to treat adrenal insufficiency and to decrease elevated androgen hormone levels. It is essential in allowing for normal growth and puberty in children. Hydrocortisone regulates menstrual cycles and promotes fertility in adult females. With proper treatment patients may have a normal life expectancy.