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.