Ketone body metabolism and its defects

Area of Science:

• Biochemistry
• Metabolic Disorders
• Human Physiology

Background:

• Ketone bodies, acetoacetate (AcAc) and 3-hydroxybutyrate (3HB), are key energy substrates transported from the liver.
• Their levels are critical during fasting when glucose is scarce.
• Evaluation requires clinical context like fasting duration and ketogenic stress, alongside blood glucose and free fatty acids (FFA).

Purpose of the Study:

• To review recent data on the clinical presentation, metabolite profiles, and disease course of ketone body metabolism defects.
• To highlight the diagnostic challenges and clinical significance of these disorders in adults and pregnancy.

Main Methods:

• Review of recent clinical data and metabolite profiles.
• Analysis of diagnostic criteria and clinical presentations for ketogenesis and ketolysis defects.

Main Results:

• Defects in ketogenesis include mitochondrial HMG-CoA synthase (mHS) and HMG-CoA lyase (HL) deficiency.
• Defects in ketolysis include succinyl-CoA-3-oxoacid CoA transferase (SCOT) and beta-ketothiolase (T2) deficiency.
• HL deficiency can cause hypoglycemia and neurological issues in adults; SCOT deficiency often presents with permanent ketosis, while T2 deficiency poses diagnostic challenges, especially with mild mutations.

Conclusions:

• Accurate assessment of blood total ketone bodies (TKB) requires considering clinical history and other metabolites like FFA.
• Understanding the nuances of mHS, HL, SCOT, and T2 deficiencies is vital for timely diagnosis and management.
• Diagnostic strategies, particularly for T2 deficiency, need refinement for effective newborn screening and adult patient care.