Differential Diagnosis for Pratyush

Based on the provided clinical presentation, biochemical, and metabolic profile, the following differential diagnoses are considered:

• Single Most Likely Diagnosis
  • Autism Spectrum Disorder (ASD): The patient's symptoms such as poor interoception and proprioception, regression of speech, picky eating, poor eye contact, stimming, and sensory seeking behaviors are consistent with ASD. The improvement in sleep, aggression, and comprehension after starting supplements and metabolic supports also suggests a metabolic component that is often seen in ASD.
• Other Likely Diagnoses
  • Mitochondrial Disorder: The patient's Krebs cycle abnormalities, elevated succinate, and borderline CoQ10 and lipoic acid levels suggest a mitochondrial disorder. The clinical response to carnitine and CoQ10 supplements also supports this diagnosis.
  • Pyruvate Dehydrogenase Complex (PDHC) Deficiency: The patient's elevated lactate and pyruvate levels, as well as the regression of speech and motor skills, are consistent with PDHC deficiency.
  • Biotinidase Deficiency: The patient's symptoms such as seizures, developmental delay, and skin rashes (not mentioned but possible) are consistent with biotinidase deficiency. The elevated 3-HIA and 2-HIA levels also support this diagnosis.
• Do Not Miss Diagnoses
  • Krabbe Disease: Although the patient's symptoms do not fully align with Krabbe disease, the possibility of a lysosomal storage disorder should not be missed. Krabbe disease can present with developmental delay, regression, and seizures.
  • Mucopolysaccharidosis (MPS): The patient's symptoms such as developmental delay, regression, and coarse facial features (not mentioned but possible) are consistent with MPS. The possibility of a lysosomal storage disorder should not be missed.
• Rare Diagnoses
  • 2-Ketoadipic Aciduria: The patient's elevated 2-HIA level is consistent with 2-ketoadipic aciduria, a rare organic aciduria.
  • Glutamic Aciduria Type 1: The patient's elevated glutamine level is consistent with glutamic aciduria type 1, a rare organic aciduria.
  • Carnitine Palmitoyltransferase (CPT) Deficiency: The patient's borderline carnitine level and clinical response to carnitine supplements suggest CPT deficiency.

Genetic Involvement

The patient's symptoms and biochemical profile suggest a possible genetic involvement. The following genes may be tested:

• SLC25A12 (mitochondrial aspartate glutamate carrier 1)
• PDHA1 (pyruvate dehydrogenase E1 alpha 1)
• BTD (biotinidase)
• GALC (galactosylceramidase)
• IDUA (alpha-L-iduronidase)
• CPT1A (carnitine palmitoyltransferase 1A)
• CPT2 (carnitine palmitoyltransferase 2)

Epigenetic Involvement

Epigenetic factors may also play a role in the patient's symptoms. The patient's severe vitamin D deficiency and elevated homocysteine level may suggest an epigenetic component. Further testing for epigenetic markers such as DNA methylation and histone modification may be considered.

Note: The above differential diagnosis is based on the provided clinical presentation and biochemical profile. A comprehensive diagnostic evaluation, including genetic testing and further biochemical analysis, is necessary to confirm the diagnosis.