Differential Diagnosis

The patient's presentation of low lactic acid, succinic acid, and citric acid in urine, along with elevated serum lactate, normal pyruvate, and low serum citric acid, suggests a complex metabolic disorder. Here's a categorized differential diagnosis:

• Single Most Likely Diagnosis

  • Mitochondrial Disease: The elevated lactate to pyruvate ratio (L:P = 28) in serum, indicative of impaired mitochondrial function, combined with the abnormalities in organic acid levels, points towards a mitochondrial disorder affecting energy metabolism.

• Other Likely Diagnoses

  • Ketogenic Diet or Fasting State: Could lead to changes in organic acid profiles due to altered metabolic states, potentially causing low levels of certain organic acids in urine and changes in serum lactate and citrate levels.
  • Renal Tubular Acidosis Type 2 (RTA2): Although the question hints at RTA2, the provided information doesn't strongly support this diagnosis as the primary issue. RTA2 typically involves a failure to acidify urine, but the organic acid abnormalities and serum lactate elevation suggest a more complex metabolic issue.
  • Pyruvate Dehydrogenase Complex (PDH) Deficiency: This condition affects the conversion of pyruvate to acetyl-CoA, potentially leading to elevated lactate levels and altered organic acid profiles.

• Do Not Miss

  • Diabetic Ketoacidosis (DKA): Although less likely given the specific pattern of organic acid abnormalities, DKA can cause significant alterations in metabolic profiles, including lactate and organic acid levels. It's crucial to rule out DKA due to its acute severity.
  • Lactic Acidosis due to Medication or Toxin: Certain medications and toxins can cause lactic acidosis, which might present with elevated serum lactate and could potentially affect organic acid levels.

• Rare Diagnoses

  • Succinyl-CoA Synthetase Deficiency: A rare disorder affecting the citric acid cycle, which could potentially explain abnormalities in succinic acid levels, though it's less likely given the broader metabolic disturbances.
  • Citrate Transporter Deficiency: A rare condition that could lead to low citric acid levels in plasma, though it would not fully explain the other metabolic abnormalities.
  • Other Organic Acidemias: Various rare genetic disorders affecting organic acid metabolism could present with similar profiles, though they are less common and would require specific diagnostic testing to confirm.

Determining whether succinic acid is high or low in serum would typically require direct measurement. The patient's profile suggests a complex disorder of energy metabolism, with mitochondrial disease being a leading consideration. Low citric acid in plasma can be due to various factors, including impaired citric acid cycle function, increased renal excretion, or altered metabolic states such as fasting or ketogenic diets. RTA2 might be considered but does not fully explain the metabolic disturbances described.