Table 3.

Clinical features suggestive of inherited metabolic disorders (IMDs) and suggested metabolic testing that could be done while awaiting metabolics (or other specialist) consultation

Clinical feature	Major groups of IMDs to consider	Targeted metabolic testing If URGENT, clearly indicate on the requisitions when ordering tests
Developmental plateau or regression in the context of an abnormal neurological exam	LSD, peroxisomal disorders (X-ALD), UCD, HCYS	Ammonia, blood gas, lactate, PAA, UOA, TPH, urine MPS, VLCFA†
Altered level of consciousness, especially if episodic; stroke-like episodes	UCD, MSUD, HCYS, organic acidurias, mitochondrial disorders	Ammonia, blood gas, glucose, lactate, electrolytes, anion gap, PAA, TPH, ACP, UOA
Movement disorder (ataxia, dystonia, choreoathetosis, myoclonus, tremor)	Organic acidurias, HCYS, creatine disorders, LSD, Wilson disease	Blood gas, lactate, glucose, ACP, PAA, UOA, TPH, urine MPS, creatine panel†, copper, ceruloplasmin
MRI/MRS brain abnormality (eg, white matter change, abnormal cerebellum / basal ganglia)	Peroxisomal disorders, organic acidurias, LSD	Metabolic testing tailored to MRI findings by metabolic/genetic specialist
Hepatomegaly, splenomegaly*	LSD, peroxisomal disorders	Urine MPS (if other systemic abnormalities noted*), VLCFA†
Specific food aversions: avoiding high protein foods	UCD, MSUD and organic acidurias	PAA, ammonia, UOA, ACP
Ophthalmological findings (most common: cataracts, dislocated lens, corneal depositions, retinopathy, cherry red spot)	Galactosaemia, Lowe disease, sulfite oxidase deficiency, HCYS, LSD, peroxisomal disorders	Metabolic testing tailored to ophthalmological findings by metabolic/genetic specialist
Seizures: drug resistant, myoclonic or neonatal	UCD, organic acidurias, HCYS, creatine disorders, vitamin-dependent epilepsies, peroxisomal disorders, Menkes disorder	Ammonia, blood gas, glucose, lactate, electrolytes, anion gap, PAA, UOA, TPH, creatine panel†, VLCFA†
Abnormal tone (hypotonia or spasticity)	Organic acidurias, HCYS, creatine disorders, UCD (eg, arginase deficiency and HHH), biotinidase deficiency, peroxisomal disorders, LSD	Ammonia, blood gas, glucose, lactate, electrolytes, anion gap, PAA, UOA, TPH, VLCFA†, creatine panel†
Coarse facial features and/or skeletal abnormalities on X-ray*	MPS and other storage disorders	Urine MPS
Multisystemic involvement	LSD, mitochondrial disorders, peroxisomal disorders, CDG, SLOS	Metabolic testing tailored to specific findings by metabolic/genetic specialist

X-linked ALD (adrenoleukodystrophy).^135–137

Highly specialised tests that are not recommended for initial workup are not included.

*For mucopolysaccharidoses (MPS), look for noisy breathing, short stature, macrocephaly and sensorineural hearing impairment. For MPS III (Sanfilippo syndrome), aggressive behaviour, sleep disturbance and hirsutism may be early features.

†Test ordering may be restricted to certain specialists.

ACP, acylcarnitine profile; CDG, congenital disorders of glycosylation; HCYS, homocystinuria and remethylation/cobalamin disorders; HHH, hyperornithinaemia hyperammonaemia homocitrullinuria syndrome; LSD, lysosomal storage disorder; MRS, Magnetic resonance spectroscopy; MSUD, maple syrup urine disease; PAA, plasma amino acids; SLOS, Smith-Lemli-Opitz syndrome; TPH, total plasma homocysteine; UCD, urea cycle disorder; UOA, urine organic acids; VLCFA, very long chain fatty acids.