Use of a long-chain triglyceride-restricted/medium-chain triglyceride-supplemented diet in a case of malonyl-CoA decarboxylase deficiency with cardiomyopathy.

Malonyl coenzyme A (CoA) decarboxylase (EC 4.1.1.9, MCD) deficiency, or malonic aciduria, is a rare inborn error of metabolism characterised by a variable phenotype of developmental delay, seizures, cardiomyopathy and acidosis. There is no consensus for dietary treatment in this condition. This case describes the effect of a long-chain triglyceride (LCT)-restricted/medium-chain triglyceride (MCT)-supplemented diet upon the progress of an affected child. A full-term Asian girl of birth weight 3590 g was screened for malonic aciduria after birth due to a positive family history. She had elevated urine malonic and methylmalonic acids and was presumably homozygous for a deleterious mutation in the MLYCD gene. Her echocardiography showed mild cardiomyopathy at 0.5 months of age, but heart function was good. She was treated with carnitine 100 mg/kg per day and continued a high-energy formula feed, as her growth was slow. At 3 months of age, echocardiography showed deteriorating cardiac function with a fractional shortening of 18%. She started an angiotensin-converting enzyme (ACE) inhibitor (Captopril). Over the next few months, her diet was altered to comprise 1.9% energy from LCT, 25% from MCT and the remainder carbohydrate. Cardiac function improved and was optimal at 23 months of age, with a fractional shortening of 28% and good systolic function. During a period of low MCT intake, her cardiac function was noted to deteriorate. This reversed and stabilised following reinstatement of the diet. This case of malonic aciduria with cardiomyopathy demonstrates improvement in cardiac function attributable to LCT-restricted/MCT-supplemented diet.

Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late presentation and literature review.

The congenital disorders of glycosylation (CDG) are a recently described group of inherited multisystem disorders characterized by defects predominantly of N- and O-glycosylation of proteins. Cardiomyopathy in CDG has previously been described in several subtypes; it is usually associated with high morbidity and mortality and the majority of cases present in the first 2 years of life. This is the first case with presentation in late childhood and the article reviews current literature. An 11-year-old female with a background of learning difficulties presented in cardiac failure secondary to severe dilated cardiomyopathy. Prior to the diagnosis of CDG, her condition deteriorated; she required mechanical support (Excor Berlin Heart) and was listed for cardiac transplant. Investigations included screening for glycosylation disorders, and isoelectric focusing of transferrin revealed an abnormal type 1 pattern. Analysis of phosphomannomutase and phosphomannose isomerase showed normal enzyme activity, excluding PMM2 (CDG Ia) and MPI (CDG Ib). Lipid-linked oligosaccharide and mutational studies have not yet defined the defect. Despite aggressive therapy there were persistent difficulties achieving adequate anticoagulation and she developed multiple life-threatening thrombotic complications. She was removed from the transplant list and died from overwhelming sepsis 5 weeks following admission. This case emphasizes the need to screen all children with an undiagnosed cardiomyopathy for CDG, regardless of age, and where possible to exclude CDG before the use of cardiac bridging devices. It highlights the many practical and ethical challenges that may be encountered where clinical knowledge and experience are still evolving.

Mitochondrial disorders and general anaesthesia: a case series and review.

Patients with mitochondrial disease are at risk of metabolic decompensation and often require general anaesthesia (GA) as part of their diagnostic work up and subsequent management. However, the evidence base for the use of GA is limited and inconclusive. We have documented the practice and outcome in the use of GA in paediatric patients with mitochondrial disease using a retrospective case review study of 38 mitochondrial patients who had undergone 58 anaesthetics within the regional metabolic service for the period 1989-2005. A variety of anaesthetic agents were used and the pattern of use reflects that seen in standard paediatric practice. There were no episodes of malignant hyperthermia and no documented intraoperative events attributable to the GA. Three postoperative adverse events were noted; one episode of hypovolaemia, one episode of acute on chronic renal failure, and one episode of metabolic decompensation 12 h post-muscle biopsy. Despite theoretical concern about this group of patients, adverse events after GA are rare and in most cases unrelated to the anaesthesia. Further prospective studies of GA in mitochondrial disease are required to create evidence-based clinical guidelines for safe practice.