#	Presentation	Think…	Pearl
1	Acute encephalopathy + hyperammonemia	UCD / OA / FAOD	Treat ammonia, don't wait
2	Lactic acidosis, elevated L:P ratio	Mito / PDH	Single normal lactate doesn't exclude
3	Episodic ataxia / movement crisis	MSUD / OA / mito / UCD / GLUT1	Timing relative to meals is critical
4	Regression after febrile illness	Intoxication IEM / Rett	Partial recovery favors IEM
5	Normal MRI + regression	Early IEM / GLUT1 / creatine / NKH	Normal MRI does NOT exclude IEM
6	Progressive leukodystrophy	MLD / Krabbe / X-ALD / Alexander / VWM	MRI pattern narrows the DDx
7	Cherry-red spot	GM1 / GM2 / NPA / sialidosis	Absence doesn't exclude LSD
8	HSM + neuro decline	NPC / Gaucher 3 / GM1 / MPS	NPC: VSGP classic but subtle
9	Refractory neonatal seizures	PDE / PNPO / NKH / biotinidase / MoCoD	Pyridoxine trial warranted
10	Infant hypotonia + neurodegeneration + hair/CT abnl	Menkes (ATP7A)	Low Cu/Cp; X-linked
11	Adolescent liver + BG signal + psych	Wilson (ATP7B)	KF rings absent in 50%; low Cp
12	ID + movement disorder + absent MRS creatine	Creatine deficiency (SLC6A8)	Urine Cr:creatinine ratio

Stabilize: ABCs, correct hypoglycemia, treat seizures
Acute labs: Ammonia, gas, glucose, lactate, lytes, LFTs, PAA, acylcarnitines, UOA
Categorize: Small vs large molecule, acute vs progressive, multi-organ vs brain-only
Check NBS: Was it done? Normal NBS does NOT exclude all IEMs
First-tier screen: Full panel if not done — collect DURING crisis
Treatable signal? UCD / OA / aminoacidopathy / creatine / PDE / GLUT1 / Wilson / Menkes — immediate consult
Unrevealing? Proceed to WES/WGS without delay — exhaustive sequential testing is outdated

A newborn presents at 5 days of life with poor feeding, alternating hypo- and hypertonia, and a sweet maple syrup odor to the urine. Which amino acid is most specifically elevated and pathognomonic for this condition?