Monocarboxylate Transporter 1 Deficiency

A number sign (#) is used with this entry because monocarboxylate transporter-1 deficiency (MCT1D) is caused by homozygous or heterozygous mutation in the MCT1 gene (SLC16A1; 600682) on chromosome 1p13.

Clinical Features

Van Hasselt et al. (2014) reported a girl, the second child of consanguineous Syrian parents, who presented at 3.5 months of age with respiratory distress due to a viral upper respiratory tract infection. Blood gas analysis revealed profound metabolic acidosis (pH of 6.88, base excess of -28 mmol/L, and an elevated anion gap of 33 mmol/L). After receiving sodium bicarbonate and intravenous glucose, she recovered rapidly. Cardiac ultrasound showed a hemodynamically insignificant type II atrial septal defect and a hypoplastic left pulmonary artery. Bronchoscopy identified hypoplasia and malacia of the main left bronchus. Cerebral ultrasound showed increased echogenicity of both caudate and lentiform nuclei. Borderline microcephaly was observed, and developmental delay subsequently became evident. Van Hasselt et al. (2014) also studied 8 other patients with monocarboxylate transporter 1 deficiency. All patients presented with bouts of ketoacidosis provoked by fasting or infections in the first years of life. Ketoacidotic episodes were preceded by poor feeding and vomiting and were associated with dehydration, which was a consequence of osmotic diuresis and vomiting. In all patients, treatment with intravenous glucose or dextrose, combined with bicarbonate, led to rapid clearance of metabolic acidosis. Early initiation of treatment appeared to prevent ketoacidosis, and ensuring adequate caloric intake reduced the number of episodes. The frequency of ketoacidotic episodes appeared to decrease over time, and none of the patients had documented ketoacidosis after 7 years of age, although some patients had marked ketonuria associated with mild infections.

Molecular Genetics

In their index patient, a girl of consanguineous Syrian descent with recurrent, severe acidosis, Van Hasselt et al. (2014) detected homozygosity for a frameshift mutation in the MCT1 gene (600682.0005). Van Hasselt et al. (2014) then screened 96 patients with unexplained ketoacidosis for mutations in MCT1 and identified 7 additional mutations, 2 of which occurred in homozygosity and were associated with mild to moderate intellectual disability. They identified 5 heterozygous mutations; all were frameshift or termination except 1 missense mutation that affected the catalytic site. No patient with a heterozygous mutation had evidence of intellectual disability, but 2 of these patients had migraines. It was unclear whether the intellectual disability observed in homozygous patients was caused by absence of MCT1 or by episodes of profound ketoacidosis. Homozygous patients tended to present at a younger age and had more profound ketoacidosis.