3-hydroxy-3-methylglutaryl-coenzyme a lyase deficiency: a case report

Case presentation: Male patient, 6 months old, admitted due to seizure associated with severe refractory hypoglycemia. Patient had been experiencing unusual sleepiness for 8 days, and vomiting after feedings. Brain CT showed prominence of the bilateral frontotemporal extra-axial space and of the Sylvian fissures, EEG revealed a slow diffuse moderate disturbance of the background activity and the MRI revealed extensive areas of diffusion restriction involving the white matter of the cerebral hemispheres as well as the globus pallidus and central fragmentary tracts in the brainstem, without mass effect or enhancement by the contrast. A hypothesis of inborn error of metabolism was raised and therapy was initiated with diet adjustments and L-carnitine, and, in the following days, the patient was clinically and hemodynamically stable, with no new episodes of hypoglycemia or seizures. The result of the biochemical analysis of organic acids in urine showed a marked increase in 3-hydroxy-isovaleric, glutaric, 3-methyl-glutaric, 3-methyl-glutaconic, 3-hydroxy-3-methylglutaric and 3-methyl-crotonylglycine acids. Genetic testing demonstrated 3-hydroxy-methylglutaryl-CoA lyase deficiency (3HMG) with the homozygous mutation of the HMGCL gene.

Discussion: 3HMG usually starts with a metabolic decompensation. Clinical manifestations are due to excessive consumption of glucose, since they do not have enough ketone bodies for energy consumption. Acute decompensations are mainly presented by vomiting, lethargy, hypotonia, tachypnea/apnea, metabolic acidosis, seizures, hepatomegaly and other less common manifestations, and may progress to comatose states. The hypothesis of 3HMG was raised when the metabolic alterations were added to the results of the brain images, which showed enlargement of the sylvian fissure, and globus pallidus alteration.

Final comments: 3HMG is a hereditary disease of the final metabolism of leucine and the ketogenic pathway due to an enzyme deficiency and manifests as a metabolic decompensation. The earlier the disease is discovered, the better the patient's prognosis, aiming to reduce possible complications and sequelae.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023