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[Metabolic and genetic investigations in childhood cardiomyopathies]
1Service de cardiologie pédiatrique, hôpital Necker-Enfants Malades, Paris.
Insights
Metabolic cardiomyopathy in children, often presenting with poor prognosis, requires accurate diagnosis for effective family counseling and treatment. Early identification of underlying causes like inborn errors of metabolism is crucial.
Area of Science:
- Pediatric Cardiology
- Inborn Errors of Metabolism
- Genetic Metabolic Disorders
Context:
- Metabolic cardiomyopathies constitute 15% of pediatric cardiomyopathies.
- Accurate etiological diagnosis is vital for prognosis and family counseling.
- Many metabolic cardiomyopathies have poor prognoses and are rarely curable.
Purpose:
- To highlight the diagnostic challenges and approaches for metabolic cardiomyopathies in infants and children.
- To emphasize the importance of identifying specific metabolic defects for management.
- To discuss the diagnostic criteria and methods for various metabolic cardiomyopathy subtypes.
Summary:
- Distinguishes between glycogen/mucopolysaccharide storage diseases (e.g., Pompe, Hurler) and oxidative metabolism deficits.
- Highlights diagnostic clues for oxidative metabolism deficits: family history, consanguinity, extracardiac disease, ECG, hypoglycemia.
- Mentions diagnostic tests: organic acid chromatography, acylcarnitine analysis, fatty acid oxidation studies, and mitochondrial respiratory chain analysis.
- Notes that only primary carnitine deficiencies are curable.
- Emphasizes diagnostic difficulties in mitochondrial cardiomyopathies due to complex genetic factors.
Impact:
- Facilitates earlier and more accurate diagnosis of metabolic cardiomyopathies in pediatric patients.
- Improves prognostic assessment and genetic counseling for affected families.
- Guides clinicians in suspecting and investigating metabolic etiologies in pediatric cardiomyopathy cases.
- Contributes to better understanding of the genetic and metabolic underpinnings of heart disease in children.
Abstract:
Metabolic cardiomyopathy of babies and children accounts for approximately 15% of all cardiomyopathies presenting at these ages. The confirmation of the aetiology is essential for treatment, which is rarely curative. For establishing a prognosis which is often poor, and, above all, for family counselling in cases of mendelian transmission or mitochondrial disease. Cardiomyopathy due to glycogen (Pompe's disease) or mucopolysaccharide (Hurler's disease) disorders are easy to diagnose because of obvious extracardiac manifestations. The diagnosis of the enzyme deficiency only requires a blood and/or urine test. Cardiomyopathies due to a deficit of oxidative metabolism are usually associated with multi-system abnormalities but may be isolated or the presenting sign of the deficit. The diagnosis should be suspected in cases of a positive family history of cardiomyopathy or sudden death, of co-sanguinity, of unusual or unexplained extracardiac disease, of atypical ECG changes or of hypoglycaemia. Chromatography of organic acids, analysis of acylcarnitines and -oxidation of the fatty acid oxidation. Of these conditions, only primary carnitine deficits are curable. The diagnosis of mitochondrial cardiomyopathy is based on the ratios of oxidoreduction and, above all, on spectrophotometric analysis of the respiratory chain complexes in skeletal or cardiac muscle (when the heart is the only organ involved). Genetic counselling is difficult and punctual mutations or deletions of mitochondrial DNA are rarely observed, and also few nuclear genes coding for the proteins of the respiratory chain have been identified to this day.