Condition AZ: p

Characteristic features include:

• low birth weight
• heart defects
• structural eye defects
• cleft lip and/or palate
• meningomyelocele (a spinal defect; see entry Spina Bifida)
• omphalocele (abdominal defect; see entry Abdominal Exstrophies)
• abnormal genitalia
• low-set ears
• abnormal palm creases
• scalp defects
• extra digits and overlapping of fingers over thumb
• abnormal brain development (holoprosencephaly)
• learning disability

Patau syndrome is often detected during pregnancy (see prenatal diagnosis) and some parents will opt not to continue the pregnancy. In some cases a spontaneous miscarriage will occur.

Sometimes a baby may be born with features of Patau syndrome after normal scans in the pregnancy. In this situation, a blood sample from the baby will be sent for karyotype analysis to confirm the diagnosis.

Parents should meet with the obstetric and neonatal teams to discuss the diagnosis and to prepare for delivery and the care of their baby. It is likely that the baby will be admitted to the special care baby unit, and will require supportive treatments over the first days of life. Many babies with Patau syndrome have congenital problems such as a cleft lip/palate or heart defects. They will need treatments to alleviate symptoms and improve their quality of life.

Sadly, many children with Patau syndrome will be lost during a pregnancy, are stillborn or do not survive past the first week of life. A few children will live longer than one year and there are some cases of adults with this condition. If a baby is well enough to leave hospital, community support arrangements should be put in place, and follow-up plans made with the local paediatric team.

Inheritance patterns
Patau syndrome usually happens as ‘one off’ (sporadic) event in a family. In this situation the chance of another baby with Patau syndrome in the family is low. In rare cases, a balanced translocation in a parent can give rise to an unbalanced translocation in their child. This situation is detected on the baby’s karotype.

Prenatal diagnosis
Screening for Patau syndrome is now offered at 10-14 weeks of pregnancy using a combined blood test and ultrasound scan as part of antenatal care. If this screening test gives a high risk result a further definitive test (chorionic villous sample test or amniocentesis) is offered.

Features of Patau syndrome can be detected on the routine detailed anomaly scan at 20 to 22 weeks gestation (see prenatal diagnosis section) in around 80% of cases. In this situation a definitive chromosome test will be offered. Parents may opt not to continue with the pregnancy. In many cases the baby is lost as a spontaneous miscarriage.

Information and support in the UK for Patau syndrome is provided by SOFT UK (see entry Edwards’ syndrome).

The condition is hallmarked by the four different types of episode/crises which are outlined below and patients may have any or all of them.

Birth episode
Affected babies are born red and stiff. This abates within minutes and is presumably secondary to ‘the pain of birth.’ No apnoeas (cessation of breathing) or bradycardias (heart beat slowness) are noted at the time of birth.

Rectal episode
The episode which defines the phenotype is the rectal- or lower-body episode. Defecation is almost always the sole trigger in infants and children. From birth until about eight years of age these children have paroxysms (episodes) of pain following defecation. They often become restless for a few hours prior to opening their bowels. After opening their bowels they experience a severe burning pain which starts in the anus, ascends up the rectum and spreads all over their bodies but is especially severe in the abdominal area. This pain is often accompanied by apnoea and bradycardia resembling reflex anoxic seizures which lasts up to several minutes. EEG recordings during an episode show no seizure activity. Following the reflex anoxic seizures there is the classical flushing as described above.

Although children eventually outgrow defecation induced rectal episodes, affected adults fear defecating in case an episode is triggered. Adults experience similar attacks albeit rarely. Triggers include unexpected falls, fights, sexual activity and vivid dreams but not defecation.

Ocular crisis
These are the most frequent of the crises and occur in adults and children. They are mostly paroxysmal in nature (sudden attacks); however, if provoked, a change in temperature and a cold wind are the commonest triggers. Some individuals have up to twenty a day. They describe the pain as if someone is poking red hot needles into the back of one eye. This lasts for up to thirty seconds and resolves spontaneously. After this the eye waters, the pupil dilates and there is flushing on that side of the face.

Mandibular/facial crisis
Typically these occur in older children and adults and are often triggered by the first mouthful of food at a meal. Yawning is also a common trigger. Patients may experience a burning pain over the jaw area on one side of the face. It may spread round the back of the neck, and up to the ipsilateral eye (on the same side). In these instances there is an overlap with the ocular crisis. Once the pain abates the skin over the jaw area flushes and the nostril on the same side runs.

Diagnosis is based on a careful history, a normal examination and normal EEG (electroencephalogram), ECG (electrocardiogram) and nerve conduction studies.

In children, it has been important to manage the inevitable constipation that ensues from stool withholding secondary to fear of defecation. The episodes themselves respond to medication useful in the management of chronic neuropathic pain disorders – namely anticonvulsants. Carbamazepine is the most effective of these.

Inheritance patterns
Autosomal dominant. Mutations in the sodium channel gene SCN9A cause paroxysmal extreme pain disorder in several families

Prenatal diagnosis
In a family where the mutation is known it is possible to offer prenatal diagnosis.

Families can use Contact’s freephone helpline for advice and information To meet other families with disabled children, join Contact’s closed (private) Facebook group.

People with acute pancreatitis suffer moderate to severe pain in the upper abdomen. This comes on suddenly and usually also moves through to the back. There is a feeling of sickness (nausea) and often vomiting with loss of appetite. There is tenderness on touching the abdomen and the pain will force people to lie down and be still. Lots of fluid moves into the inflamed tissues and may cause a fall in blood pressure making the person become sweaty and feverish. These symptoms gradually resolve in most people over a few days to a week.

In severe cases the lungs and kidneys become seriously damaged and the pancreas gland may be partly or completely destroyed in a form of gangrene (pancreatic necrosis) and if untreated will cause death.

The main causes are gallstones or alcohol but also injury by accidents or instrumentation, medications and infections. In about 1% this is due to inherited genes.

By measuring the level of a pancreas enzyme (amylase) from a blood sample, and in severe cases using a computerized tomography (CT body) scan.

Fluid is replaced by using a vein drip, along with injections to relieve pain. Pulse rate, blood pressure and urine output are also regularly measured. In severe cases, treatment will be needed on an intensive care unit. Dead and infected pancreatic tissue will be removed by inserting tubes and instruments and surgery.

To avoid recurrent attacks the gallbladder should be removed if due to gallstones and abstinence if due to alcohol.

Inheritance patterns
An altered PRSS1 gene causes inherited pancreatitis with 30-40% of individuals in a family developing symptoms. Other inherited genetic alterations just increase the risk without affecting multiple family members (SPINK1, CFTR and CLDN2).

Prenatal diagnosis
Not applicable.

Pancreatitis Supporters Network

Tel: 07949 973430
Email: [email protected]
Website: pancreatitis.org.uk

The Network is a Registered Charity in England and Wales No. 1027443. It provides information and support to anyone affected by pancreatitis. The Network runs an online discussion forum and a pen pal scheme.

Group details last updated February 2016.

The main features include

• hypotonia (floppiness)
• a distinctive appearance, with a high, rounded forehead, widely spaced eyes and a large mouth with a thin upper vermillion (lip)
• streaks or patches of darker (hyperpigmentation) or lighter (hypopigmentation) skin
• developmental delay (see entry Global Developmental Delay); varies from mild to severe
• learning difficulties (see entry Learning Disability)
• epilepsy
• sparse hair or bald patches around the temples, and sparse eyebrows.

A number of other features may be associated with PKS, including heart defects, gastro-oesophageal reflux, umbilical hernia, missing teeth and hearing and vision problems. Diaphragmatic hernia occurs when there is a hole in the muscle that separates the contents of the abdomen from the chest, so part of the gut may develop in the chest, leaving too little room for the lungs to grow. This occurs more frequently in babies with PKS.

A chromosome is a thread-like structure that is present in the nucleus of cells. Usually individuals have 23 pairs of chromosomes (46 chromosomes in each cell). Individuals with PKS have an extra chromosome made up of material from the twelfth pair of chromosomes in some cells, so 47 in total. The extra material from chromosome 12 is not present in all body cells, so the condition is described as a mosaic.

PKS is usually diagnosed after birth. Chromosome studies in a blood sample often produce a normal result in PKS due to mosaicism. Other tissues such as skin or the mucous covering of the inside of the mouth, are more likely to reveal the additional chromosome. Often, a buccal smear (where cells are scraped from the inner side of the cheeks) is taken first, and if this does not give a useful result a skin biopsy is taken.

There is no cure for the condition. Management involves providing medical support for the features of PKS, as well as appropriate education, emotional and social support. Some babies may be severely affected by diaphragmatic hernia and this may need immediate surgery. Heart defects may also require surgery. Seizures typically need to be controlled with medication. Regular checks of the child will be needed to assess their level of development and vision and hearing. Most (but not all) people will PKS will require care throughout their lives.

Inheritance patterns
PKS occurs sporadically, meaning no other family member is usually affected.

Prenatal diagnosis
Abnormalities on an ultrasound scan, such as short arms and legs, a diaphragmatic hernia, heart defect or polyhydramnios (too much fluid around the baby) may be observed. A mother can then be offered a chorionic villus sampling test (CVS) test to look for the extra chromosome 12 material.

Information and support in the UK for Pallister-Killian syndrome is provided by Unique (see entry Chromosome disorders).

There is no support group for Pallister-Hall syndrome in the UK. Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families. To meet other families with disabled children, join Contact’s closed (private) Facebook group.

Infantile-onset Pompe disease
This becomes apparent from within a few days to a few months of birth. Infants typically experience myopathy (muscle weakness), hypotonia (poor muscle tone), and a severe thickening of the heart muscle called hypertrophic cardiomyopathy (see entry Cardiomyopathies in Children). The cardiomyopathy results in heart failure (i.e. accumulation of fluids on the lungs) and hepatomegaly (an enlarged liver). The combination of heart failure and with the decreased muscle strength means that children often have with breathing difficulties. Affected infants will also fail to gain weight and grow as expected. They also can suffer from swallowing difficulties. Sadly, if left untreated, this form of Pompe disease can lead to death from heart failure in the first year of life.

Non-classic Infantile-onset Pompe disease
This form of infantile-onset Pompe disease also appears by one year of age. Symptoms are the same as infant-onset except for the absence of the cardiomyopathy.

Late-onset Pompe disease
The late-onset type of Pompe disease may not become apparent until later in childhood, adolescence or more commonly adulthood. Late-onset Pompe disease is usually milder than the infantile-onset forms of this condition and again does not involve the heart. Most individuals with late-onset Pompe disease experience progressive muscle weakness, especially in the legs and the trunk and including the muscles that control breathing. As the condition progresses, breathing problems can become more serious.

Changes to the GAA gene (known as mutations) cause Pompe disease. The GAA gene provides instructions for producing an enzyme called acid alpha-glucosidase (also known as acid maltase). This enzyme normally breaks down glycogen in a specialised region of the cell that normally recycles worn out cellular components. This part of the cell is called the lysosome.

In order to diagnose the condition conclusively, an enzyme assay test must be carried out. The test looks at the levels of acid alpha-glucosidase enzyme in the affected child. This can now be done on a simple blood spot test similar to that used in routine newborn screening. All patients will then be referred to a specialised treatment centre for further investigations and assessments.

An enzyme replacement therapy (ERT), called alglucosidase alfa (Myozyme) has been developed. The ERT is available in England by referral to one of the expert centres for lysosomal storage disease. NHS funding for this very expensive therapy is not assured for every patient and in Scotland it is still proving very difficult for some late-onset patients to access the therapy. It is worth noting that any previous organ damage that occurs prior to treatment is irreversible.

Inheritance patterns 
The condition is inherited in an autosomal recessive manner.

Prenatal diagnosis 
This is available if the genetic mutation in the family has been identified. Affected families should be referred to a genetic service for further information and support.

Pompe Support Network

Tel: 01730 231554
Email: [email protected]
Website: pompe.uk

The Pompe Support Network are a Charitable Incorporated Organisation (CIO) no. 1186383. The Pompe Support Network aims to benefit the whole Pompe community in many ways including: monitoring and supporting research, sharing information and representing the patient voice across industry, research and the NHS. They also offer several Facebook groups including ones for diet and nutrition, Exercise and Mental Wellbeing.

Group details added December 2019

Information and advice in the UK for Pompe disease is also provided by the Association for Glycogen Storage Diseases (UK) (see entry Glycogen Storage diseases).

For those purine and pyrimidine disorders that do present with symptoms, almost any system can be affected. Particular problems include kidney stones and renal disease (see entry Kidney disease), recurrent infections and severe immune deficiency, severe recurrent anaemia (anemia – US), muscle cramps and wasting, arthritis, neurological problems such as developmental delay, autism (see entry Autism Spectrum conditions) and seizures (see entry Epilepsy). They may also be responsible for adverse reactions to chemotherapy in patients undergoing treatment for cancer. Although originally thought to be childhood problems, it is clear that they may present at any age.

Symptoms may be severe and life-threatening.

Specific treatment is only available for a small number of these conditions at present.

Inheritance patterns
The mode of inheritance of these disorders is autosomal recessive, except Lesch Nyhan syndrome (HPRT deficiency) and phosphoribosylpyrophosphatesynthetase superactivity (PRPS) which are X-linked conditions, and familial juvenile hyperuricaemic nephropathy which is dominant. The degree of severity may be highly variable, even within the same family.

Prenatal diagnosis
Prenatal diagnosis is available for some of the purine and pyrimidine disorders.

Information and support in the UK for Purine and Pyrimidine Metabolic diseases is available from Metabolic Support UK (see entry Inherited Metabolic diseases).

Immunodeficiency UK

Helpline: 0800 987 8986
Email: [email protected]
Website: www.immunodeficiencyuk.org

Immunodeficiency UK is a national organisation supporting individuals and families affected by primary immunodeficiencies (PIDs) and secondary immunodeficiency (SID).

Group details last updated February 2024.