Condition AZ: f

The most serious complication of hypertriglyceridaemia is acute pancreatitis. This occurs when the pancreas becomes inflamed and releases digestive enzymes into the abdomen causing damage. Pancreatitis causes very severe abdominal pain and can be life-threatening.

Many people with hypertriglyceridaemia experience abdominal pain because of long term inflammation of the pancreas. The liver and spleen may be enlarged and there may be fatty lumps in the skin (called eruptive xanthomas) often round the elbows and knees.

Hypertriglyceridaemia with excessive chylomicrons in the blood is usually a genetic disease. There may be an inherited deficiency of the enzyme lipoprotein lipase caused by mutation in the LPL gene, or more rarely of the protein apo C-II caused by mutations in the APOC2 gene. These disorders are very rare, affecting about 1 in every one million people in the UK, although more people from Asia are affected.

Hypertriglyceridaemia is diagnosed by a blood test to measure triglyceride levels. Special blood tests can be used to measure lipoprotein lipase and apo C-II levels, or genetic testing may be used to find the gene defect.

Some children are diagnosed when they have a blood tests and their blood plasma looks abnormally creamy.

Treatment is aimed at lowering blood triglycerides to a safe level. A very low fat diet is the main part of treatment. This should be supervised by an experienced dietician. Special fats called medium chain triglycerides (MCT) can be used in infant formulas or as dietary supplements to provide energy and MCT may help to reduce triglyceride levels. Fat soluble vitamins and essential fatty acids (often as walnut oil) should be given as supplements.

Inheritance patterns
Lipoprotein lipase and apo C-II deficiencies are recessively inherited – both parents carry one copy of a mutant LPL or APOC2 gene, and the affected child inherits the mutated gene from each unaffected carrier parent.

Prenatal diagnosis
Prenatal diagnosis is possible if the gene mutation is known, although it is rarely requested as effective treatment is available.

Information and support in the UK for organic acidaemias is provided by Metabolic Support UK (see entry Inherited Metabolic diseases).

Onset is usually between the ages of 4 and 16 years (but occasionally between 18 months and 50 years). The first symptom is usually gait ataxia or difficulty in walking.

The ataxia gradually worsens and spreads but the arms may remain relatively unaffected for a long period. The legs are most commonly affected, so that individuals often have to use a wheelchair in the advanced stages of the condition. There is often loss of position sense in the hands and feet. Individuals who develop FA at a young age may also develop skeletal problems such as curvature of the spine (called scoliosis) or high-arched feet (called pes cavus).

Dysarthria (slowness and slurring of speech) and dysphagia (problems with swallowing) can develop and become progressively worse. Individuals with FA often have abnormal eye movements (called nystagmus) and some may develop hearing and visual loss.

Various forms of heart disease can accompany FA, particularly thickening of the heart muscle (hypertrophic cardiomyopathy) which can cause problems with the pumping power of the heart and irregularities of heart rhythm (arrhythmias). Diabetes may also develop (see entry Diabetes Mellitus).

The genetic change (mutation) in the majority of individuals (97 per cent plus) is an abnormally long repetition of a DNA fragment (called a GAA repeat) in the Friedreich’s ataxia gene on chromosome 9. As this is a recessive condition, you have to have a double dose of mutated genes, in both chromosomes 9, to develop the condition.

This requires clinical assessment, including a medical history and thorough physical examination. Genetic testing (by blood test) provides a conclusive diagnosis.

Many of the symptoms of FA can be treated to help individuals maintain a good quality of life. Doctors can prescribe treatments for diabetes and heart problems, if present. Problems such as foot deformities and scoliosis can be corrected with braces or surgery. Physical therapy may prolong use of the arms and legs. There is currently no cure for FA or treatment that slows the degenerative process.

Advances in understanding the genetics of FA are leading to breakthroughs in treatment. Clinical trials of several proposed treatments have already occurred and further trials are currently underway.

Inheritance patterns
FA is inherited in an autosomal recessive manner.

Prenatal diagnosis
Prenatal diagnosis is also possible via chorionic villus sampling for families where the mutation causing the condition is known. It is also possible to test unaffected individuals in affected families to see if they carry the mutation that causes the condition. Affected families should be referred to a genetics centre for information and advice.

Ataxia UK

Helpline: 0800 995 6037
Email: help@ataxia.org.uk
Website: ataxia.org.uk

The Organisation is a Registered Charity in England and Wales No. 1102391, established in 1964. It supports people affected by Friedreich’s, cerebellar and other ataxias, their carers, families and friends, to live with the condition. The Organisation provides information, a helpline, a network of local branches and self-help groups, contact with other affected families and welfare grants. It also supports medical and scientific research into causes and potential treatments.

Group details last updated March 2024.

Children with Freeman Sheldon syndrome may have:

• Distinctive facial appearance, including:

– microstomia (a small mouth) with pursed lips – giving the appearance of a ‘whistling face’
– prominent forehead and brow ridges
– mid-face hypoplasia (a sunken appearance of the middle of
the face)
– a short nose, and a long philtrum (area between the nose
and mouth)
– hypoglossia (unusually small tongue)
– micrognathia (small jaw)
– a high arch in the roof of the mouth (high-arched palate).

• Eye problems, including:

– hypertelorism (widely spaced eyes)
– deep set eyes
– down-slanting palpebral fissures (outside corners of the eyes that point downward)
– blepharophimosis (a narrowing of the eye opening)
– ptosis (droopy eyelids)
– strabismus (a squint, ie eyes that do not look in the same direction).

• Joint problems and bone problems, including:

– joint contractures (deformities) that restrict movement such as distal arthrogryposis  (multiple contractures in the hands and feet at birth)
– camptodactyly (permanently bent fingers and toes) due to contractures
– ulnar deviation  (a hand deformity in which all of the fingers are angled outward)
– clubfoot (inward- and downward-turning feet)
– curvature of the spine (scoliosis).

• Affected children may also experience:

– a failure to gain weight and grow at the expected rate (failure to thrive)
– speech problems
– hearing loss.

Children affected by Freeman-Sheldon syndrome may also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia.

Intelligence is unaffected in most people with Freeman-Sheldon syndrome, but around one-third have some degree of learning disability.

Freeman-Sheldon syndrome may be caused by mutations in the MYH3 gene. The MYH3 gene provides instructions for making a protein called embryonic skeletal muscle myosin heavy chain 3. This protein belongs to a group of proteins called myosins, which are important for muscle development and function.

Freeman-Sheldon syndrome is usually diagnosed on the combination of problems, such as the contraction of the joints and the appearance of the face. Genetic testing for the MYH3 gene may help if the diagnosis is uncertain.

Treatment for the condition consists of reducing the affects of the symptoms, therefore improving quality of life. Babies often need help with feeding in infancy and nutritional support. Growth should be monitored by a paediatrician through childhood. Physiotherapy should be used to alleviate the joint contractures and occupational therapy is often helpful. Many people require orthopaedic surgery to relieve joint contractures and improve function and mobility.

Glue ear can be a problem and is treated with grommets by an ear, nose and throat (ENT) specialist. A squint should be treated in the same way as in other children.

There may be malocclusion (misalignment) of the teeth and orthodontic treatment of this may be required. Opening the mouth fully for dental treatment may be difficult.

Inheritance patterns
Freeman Sheldon syndrome is usually inherited as an autosomal dominant trait, although often a child is the first member of the family to be affected. Affected families should be referred to a genetics centre for information and support

Prenatal diagnosis
Prenatal diagnosis would be available if the genetic alteration in the family is known.

Information and support in the UK for Freeman Sheldon syndrome is provided by steps (see entry Lower Limb Abnormalities).

A support group outside of the UK exists for Freeman Sheldon syndrome, please ring our helpline for details. To meet other families with disabled children, join Contact’s closed (private) Facebook group.