In children with mitochondrial disease, cardiomyopathy was common (17%) and was associated with increased mortality. The prognosis for children with cytochrome-c oxidase deficiency and cardiomyopathy appeared to be particularly unfavorable.

In families with HCM, children should be screened at an early age.

Children at high risk of dying suddenly with hypertrophic cardiomyopathy, with a subsequent annual mortality of 6.6%, can be distinguished at the time of diagnosis from those patients having a low risk of sudden death, the latter with an annual mortality of 0.27%.

Aim: To study whether natriuretic peptide types B (BNP) and A (ANP) reflect clinical signs of heart failure (CSHF) in children with congenital heart defects or cardiomyopathy resulting in different types of haemodynamic situations, such as pressure overload in coarctation of the aorta (CoA), volume overload in ventricular septal defect (VSD) or systolic dysfunction in dilated cardiomyopathy (DCM). Methods: Blood samples for plasma P‐BNP and P‐ANP were taken before procedures during regular investigation from 26 children (9 CoA, 11 VSD and 6 DCM). The ordinary paediatric cardiologist performed the cardiac evaluation and the data were retrieved from medical charts. CSHF was considered positive if two of the following criteria were fulfilled: reduced physical capacity, feeding disorders, dyspnoea, tachypnoea, hepatomegaly and oedema. The statistical methods were non‐parametric. Results: 0/9 children with CoA, 5/11 with VSD and 6/6 with DCM had CSHF. In children with CSHF, P‐BNP and P‐ANP were higher, 263 ng l−1 (range 47.5–1300) and 303 ng l−1 (range 168–466), than in those without CSHF, 12.3 ng l−1 (range 4.8–30.8) and 42.9 ng l1 (range 13.7–189), respectively (p < 0.001, Mann‐Whitney U‐test), irrespective of the diagnosis. The same relationship was also found in the group of children with VSD. Conclusion: Plasma levels of ANP and BNP increase in children with CSHF. This increase is seen irrespective of whether it is due to systolic dysfunction, as in children with DCM, or to a volume overload with a normal systolic function, as in children with VSD.

Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The disease has so far only been identified in northern Sweden. The clinical, histochemical and biochemical phenotype is very homogenous and the patients are homozygous for a deep intronic IVS5 + 382G>C splicing affecting mutation in ISCU, which encodes the differently spliced cytosolic and mitochondrial iron-sulphur cluster assembly protein IscU. Iron-sulphur cluster containing proteins are essential for iron homeostasis and respiratory chain function, with IscU being among the most conserved proteins in evolution. We identified a shared homozygous segment of only 405,000 base pair with the deep intronic mutation in eight patients with a phenotype consistent with the original description of the disease. Two other patients, two brothers, had an identical biochemical and histochemical phenotype which is probably pathognomonic for muscle iron-sulphur cluster deficiency, but they presented with a disease where the clinical phenotype was characterized by early onset of a slowly progressive severe muscle weakness, severe exercise intolerance and cardiomyopathy. The brothers were compound heterozygous for the deep intronic mutation and had a c.149 G>A missense mutation in exon 3 changing a completely conserved glycine residue to a glutamate. The missense mutation was inherited from their mother who was of Finnish descent. The intronic mutation affects mRNA splicing and results in inclusion of pseudoexons in most transcripts in muscle. The pseudoexon inclusion results in a change in the reading frame and appearance of a premature stop codon. In western blot analysis of protein extracts from fibroblasts, there was no pronounced reduction of IscU in any of the patients, but the analysis revealed that the species corresponding to mitochondrial IscU migrates slower than a species present only in whole cells. In protein extracted from isolated skeletal muscle mitochondria the western blot analysis revealed a severe deficiency of IscU in the homozygous patients and appearance of a faint new fraction that could represent a truncated protein. There was only a slight reduction of mitochondrial IscU in the compound heterozygotes, despite their severe phenotype, indicating that the IscU expressed in these patients is non-functional.