Related Experiment Videos
3-hydroxy-3-methylglutaryl-CoA lyase deficiency in an infant with macrocephaly and mild metabolic acidosis
Insights
3-HMG-CoA lyase deficiency, a metabolic disorder, was diagnosed in a 5-month-old girl. Despite treatment, she developed severe developmental delay and progressive demyelination, highlighting the condition's serious neurological impact.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Neurology
Background:
- 3-Hydroxymethylglutaryl-CoA (HMG-CoA) lyase deficiency is a rare autosomal recessive metabolic disorder.
- It is part of the ketogenesis and leucine metabolism pathways.
- Early diagnosis and management are crucial for patient outcomes.
Observation:
- A case of a 3-year-old girl diagnosed with 3-HMG-CoA lyase deficiency at 5 months is presented.
- Characteristic urinary metabolites included 3-HMG, 3-CH3-glutaconic acid, 3-CH3-glutaric acid, and 3-HIVA.
- Leukocyte 3-HMG-CoA lyase activity was significantly reduced.
Findings:
- The patient presented with compensated metabolic acidosis and mild hypoglycemia.
- A leucine-restricted diet showed moderate effects on metabolite excretion but did not resolve metabolic acidosis.
- Clinical manifestations included macrocephaly, severe developmental retardation by age 3, and progressive white matter demyelination on CAT scan.
Implications:
- This case underscores the severe neurological sequelae of 3-HMG-CoA lyase deficiency, including progressive demyelination.
- It highlights the challenges in managing metabolic acidosis and developmental outcomes even with dietary interventions.
- Further research into therapeutic strategies targeting neurological damage in this disorder is warranted.
Abstract:
A girl, now three years old, is reported, in whom at the age of 5 months the diagnosis of 3-HMG-CoA lyase deficiency was established. The characteristic excretion pattern consisted of 3-HMG, 3-CH3-glutaconic acid, 3-CH3-glutaric acid and 3-HIVA. Activity of 3-HMG-CoA lyase in leucocytes was very low. She had compensated metabolic acidosis and mild hypoglycemia. Therapy with a leucine restricted diet decreased excretion of metabolites moderately but did not influence the tendency to metabolic acidosis. Clinically the infant presented with macrocephaly. At the age of 3 years she is severely retarded. CAT scan revealed the picture of progressive demyelination of the white matter.