Monocarboxylate transporter 1 deficiency and ketone utilization.

Ketoacidosis is a potentially lethal condition caused by the imbalance between hepatic production and extrahepatic utilization of ketone bodies. We performed exome sequencing in a patient with recurrent, severe ketoacidosis and identified a homozygous frameshift mutation in the gene encoding monocarboxylate transporter 1 (SLC16A1, also called MCT1). Genetic analysis in 96 patients suspected of having ketolytic defects yielded seven additional inactivating mutations in MCT1, both homozygous and heterozygous.

Riboflavin-responsive trimethylaminuria in a patient with homocystinuria on betaine therapy.

A 17-year-old female patient with pyridoxine non-responsive homocystinuria, treated with 20 g of betaine per day, developed a strong body odour, which was described as fish-like. Urinary trimethylamine (TMA) was measured and found to be markedly increased. DNA mutation analysis revealed homozygosity for a common allelic variant in the gene coding for the TMA oxidising enzyme FMO3.

Unilateral periventricular leukomalacia in association with pyruvate dehydrogenase deficiency.

Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. A deficiency of PDH E1 alpha, a subunit of the PDH complex, is a prominent cause of congenital lactic acidosis. We describe a female infant born at term and delivered by emergency Caesarean section because of fetal distress.

Magnetic resonance spectroscopy changes following haemopoietic stem cell transplantation in children with cerebral adrenoleukodystrophy.

X-linked cerebral adrenoleukodystrophy is an aggressive, rapidly progressive disorder resulting in considerable morbidity and, left untreated, mortality. Patients typically present before the age of 10 years with progressive symptomatology including ataxia, spasticity, and focal neurological deficits. Current therapeutic options are limited, the treatment of choice being haemopoietic stem cell transplantation (HSCT).