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 featureMajor groups of IMDs to considerTargeted metabolic testing
If URGENT, clearly indicate on the requisitions when ordering tests
Developmental plateau or regression in the context of an abnormal neurological examLSD, peroxisomal disorders (X-ALD), UCD, HCYSAmmonia, blood gas, lactate, PAA, UOA, TPH, urine MPS, VLCFA†
Altered level of consciousness, especially if episodic; stroke-like episodesUCD, MSUD, HCYS, organic acidurias, mitochondrial disordersAmmonia, 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 diseaseBlood 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, LSDMetabolic testing tailored to MRI findings by metabolic/genetic specialist
Hepatomegaly, splenomegaly*LSD, peroxisomal disordersUrine MPS (if other systemic abnormalities noted*), VLCFA†
Specific food aversions: avoiding high protein foodsUCD, MSUD and organic aciduriasPAA, 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 disordersMetabolic testing tailored to ophthalmological findings by metabolic/genetic specialist
Seizures: drug resistant, myoclonic or neonatalUCD, organic acidurias, HCYS, creatine disorders, vitamin-dependent epilepsies, peroxisomal disorders, Menkes disorderAmmonia, blood gas, glucose, lactate, electrolytes, anion gap, PAA, UOA, TPH, creatine panel†,
Abnormal tone (hypotonia or spasticity)Organic acidurias, HCYS, creatine disorders, UCD (eg, arginase deficiency and HHH), biotinidase deficiency, peroxisomal disorders, LSDAmmonia, 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 disordersUrine MPS
Multisystemic involvementLSD, mitochondrial disorders, peroxisomal disorders, CDG, SLOSMetabolic 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.