Malonic Aciduria

Malonic aciduria is a metabolic disorder caused by deficiency of malonyl-CoA decarboxylase (MCD).

Epidemiology

It is a very rare disorder that has been described in less than 20 patients.

Clinical description

This condition usually presents in early childhood and the manifestations are variable. The majority of patients are developmentally delayed with other features that include hypotonia, seizures, hypoglycaemia, metabolic acidosis, cardiomyopathy and diarrhoea.

Etiology

The disease is caused by mutations in the malonyl-CoA decarboxylase gene (MLYCD, chromosome 16q24) and is inherited as an autosomal recessive trait. The MCD enzyme is involved in the degradation of malonyl-CoA and it appears that inhibition of fatty acid synthesis as a result of malonyl-CoA accumulation is responsible for at least some of the clinical manifestations of the disorder.

Diagnostic methods

The diagnosis of malonic aciduria can be made by detecting elevated levels of organic acids (in particular malonic and methylmalonic acid) in the urine and high levels of malonylcarnitine in the blood. The diagnosis is confirmed by demonstrating reduced enzyme activity in cultured skin fibroblasts. Identification of the MLYCD gene mutation may also be useful for diagnosis and for genetic counselling.

Antenatal diagnosis

Screening of newborns may be possible through detection of elevated blood levels of malonylcarnitine using electrospray ionisation tandem mass spectrometry (ESI-MS/MS). Prenatal screening is theoretically possible through enzyme or DNA analysis of amniocytes or chorionic villus samples.

Management and treatment

The principle treatment is dietary, with patients being recommended to follow a low fat/high carbohydrate diet. Carnitine supplements may also be recommended.

Prognosis

The prognosis for patients is variable but the disease can be lethal in the neonatal period.