Paediatrics: Metabolic syndromes: cardiac syndromes

Metabolic syndromes: cardiac syndromes

Cardiomyopathy 

May be the dominant or only clinical problem in a variety of IMDs.

Glycogen metabolism (hypertrophic cardiomyopathy) 

Pompe disease (GSD II)—presents in early infancy with marked skeletal myopathy, mas-sive cardiomegaly (large QRS, left axis deviation, shortened PR, T-wave inversion).

Fatty acid metabolism (dilated cardiomyopathy)

•   Systemic carnitine deficiency: presents with skeletal myopathy, hypotonia encephalopathy, hepatic syndrome (hepatomegaly, hypoglycaemia, hepatocellular dysfunction).

•   Long or very long chain acyl-CoA dehydrogenase deficiency: presents with myopathy, exercise intolerance with myoglobinuria, hypotonia, encephalopathy, hepatic syndrome 9 hyperammonaemia.

Organic acidopathy (dilated cardiomyopathy) 

Propionic acidaemia— intermittent metabolic acidosis; ketosis; hyperammonaemia; neutropenia.

Mitochondrial cardiomyopathy (hypertrophic or dilated)

Sphingolipidoses (hypertrophic cardiomyopathy) 

Fabry disease— chronic neuritis pain in hands and feet; angiokeratomata; corneal opacities; pro-gressive renal failure; cardiac arrhythmias (intermittent SVT); cerebrov-ascular disease.

Mucopolysaccharidosis (hypertrophic cardiomyopathy)

Investigation

Initial studies

•   Plasma: lactate; carnitine (free and total); acylcarnitine profile; ammonium; liver function tests; urea, creatinine, and electrolytes

•   Urine: organic acids

Suspected fatty acid oxidation defect 

Fibroblast cultures; enzyme studies

Suspected mitochondrial electron transport defect

•   Plasma: lactate/pyruvate ratio

•   CSF: lactate

•   Imaging: MRI

•   Electrophysiology: evoked potentials

•   Tissue: muscle and skin biopsy studies

Suspected lysosomal storage disease

•   Urine: mucopolysaccharide and oligosaccharide screen, glycolipids

•   Imaging: skeletal radiology

Blood: lysosomal enzyme studies

Arrhythmias

IMD-related cardiomyopathy may be complicated by arrhythmias includ-ing:

• Heart block: mitochondrial cytopathy; Fabry disease; carnitine– acylcarnitine translocase (CACT) deficiency; propionic acidaemia.

• Tachyarrhythmia: fatty acid oxidation defects; CACT.

Coronary artery disease (CAD)

CAD occurs in Fabry disease, familial hyperlipidaemias, and familial hyper-cholesterolaemia (FH).

FH affects 1/500 individuals with the following effects.

• Homozygotes: severe cholesterolaemia; ischaemic heart disease in infancy or childhood; cholesterol accumulation in the skin (tuberous xanthomas, subcutaneous nodules); and arcus senilis.

• Heterozygotes: fatal myocardial infarction in third decade.

Familial hyperlipidaemias causing premature CAD 

Familial hyperlipidaemias causing premature CAD include the following.

• Type IV: hyperlipidaemia (increased very low-density lipoproteins).

• Type IIa, familial hypercholesterolaemia: hypercholesterolaemia (increased low-density lipoproteins) with tuberous xanthomas, tendinous xanthomas, and arcus senilis.

• Type IIb: combined hyperlipidaemia (increased low- and very low-density lipoproteins).

Type III, familial dysbetalipoproteinaemia: B-very low-density lipoproteins with eruptive tuberous xanthoma, planar xanthomas, peripheral vascular disease.