Diagnosis and Treatment of Childhood Hypercholesterolaemia

Essentials

• Identification and management of children with hereditary dyslipidaemia, especially familial hypercholesterolaemia, on the basis of the parents' history of coronary heart disease and high blood lipid levels. Screening the entire child population is not recommended.

Definition of dyslipidaemia

• LDL cholesterol > 3.0 mmol/l or
• Triglycerides > 1.7 mmol/l or
• HDL cholesterol < 1.0/1.2 mmol/l in sexually mature boys/girls

Hereditary hyperlipidaemias

• The most significant of these is familial hypercholesterolaemia (FH).
  • LDL cholesterol levels abnormal since birth.
  • Can be diagnosed from the age of one year.

Secondary dyslipidaemia

• Obesity is the most common cause.
• Other causes: hypothyroidism, liver disease, kidney disease, certain storage diseases, glucocorticoids and certain other medications
• In the dyslipidaemia of metabolic syndrome associated with obesity there are usually slightly elevated cholesterol and triglyceride levels and low HDL cholesterol levels

Most important target groups for treatment

• Patients with high risk of arteriopathy, in whom prevention of coronary artery disease should be started in childhood already
  • Familial hypercholesterolaemia (FH)
  • Type 1 diabetes
  • Chronic kidney disease or kidney or heart transplant

Screening of at risk families

• Hypercholesterolaemia should be looked for in families with
  • precocious coronary heart disease at age < 55 years in men or at age < 65 years in women, or
  • a first-degree relative with diagnosed FH or hyperlipidaemia together with tendinous or cutaneous xanthomas.
• If one of the parents has FH, the children should be screened for the disease after the age of 2 but before the age of 10 years.
  • If the FH gene mutation in the family is known, the child should undergo a test for the same gene, as necessary.
  • If the FH gene mutation in the family is not known, screening should be done by determining plasma total or LDL cholesterol.
• At screening, every family member older than 2 years of age should have their cholesterol, HDL cholesterol, triglycerides and LDL cholesterol measured after a 10-12-hour fast (the LDL cholesterol can also be calculated with Friedewald's formula Ldl).
• FH is a dominantly inherited disorder, which means that at least one of the parents of a child with FH has the same disorder.
• Increased values measured at screening should be double-checked.
• Secondary causes of hyperlipidaemias should be excluded by measuring TSH, ALT and urine albumin before commencing therapy.
• If the FH gene mutation in the family has not previously been ascertained, it can be sought with tests for major mutations, which can find 80-90% of all FH-related gene defects.
• Young patients (men < 55 years, women < 65 years) with coronary heart disease and hyperlipidaemias should be informed of the importance of having their children and grandchildren examined. A general practitioner or a doctor working at an outpatient department of internal medicine may initiate targeted screening.

Diagnostic criteria of FH

• Either
  • positive result in genetic testing for FH mutations or
  • LDL cholesterol concentration repeatedly and after exclusion of secondary hyperlipidaemia > 4.0 mmol/l (or total cholesterol > 6.7 mmol/l), and the child or his/her first- or second-degree relative has tendinous xanthomas.

Therapy: indications and practice Pravastatin for Familial Hypercholesterolemia in Children

• Plasma cholesterol of less than 5.0 mmol/l (LDL < 3.0 mmol/l) does not require further action. In borderline cases, general dietary advice should be given or repeated.
• With an increased plasma cholesterol, lifestyle changes and follow-up at 3, 6 and 12 months, for example, are usually sufficient.
  • A diet based on a reduction in the intake of saturated (hard) fat and its replacement with unsaturated (soft) fat, as well as use of plant sterol (or stanol) products, forms a safe basis for diet therapy in hypercholesterolaemic children. With these measures it is possible to decrease the concentration of LDL cholesterol by 0.5-1.0 mmol/l.
  • The child should be motivated to do regular physical training and active everyday exercise, which have a beneficial effect on hyperlipidaemia.
• If such treatment for 6-12 months does not decrease plasma cholesterol to below 6.0 mmol/l or LDL cholesterol to below 4.5 mmol/l, the child should be referred to a paediatric clinic for assessment by a paediatric endocrinologist or a paediatrician familiar with the therapy of hyperlipidaemias. If necessary, a dietician should be consulted for dietary instructions.
• A child with a significantly increased cholesterol concentration should be referred directly to a paediatric clinic.
• Drug therapy is usually used only in patients with familial hypercholesterolaemia. Drug therapy is considered starting from the age of 8-10 years. The appropriate age to start the medication is essentially determined by the prevalence and severity of coronary heart disease in close relatives. The first-line drug is a statin Statins for Children with Familial Hypercholesterolemia. The assessment of the need for, and the initiation of drug therapy should be done by a paediatrician specialized in lipid disorders.

References

• Kavey RE, Allada V, Daniels SR et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2006;114(24):2710-38. [PubMed]
• Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents., National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011;128 Suppl 5():S213-56. [PubMed]