Pediatric emergency medicine trisk 607

Aminoacidopathies
Alkaptonuria
Cystinuria types I–III
Hartnup disease
Hawkinsinuria
Histidinemia
Homocystinuria types Ia, Ib, II
Nonketotic hyperglycinemia
Phenylketonuria
Tyrosinemia types I–III
Organic acidemias b
3-Hydroxy-3-methylglutaric aciduria
3-Methylcrotonylglycinuria
3-Methylglutaconic aciduria types I–IV
Biotinidase deficiency
Glutaric acidemia type I
Holocarboxylase synthetase deficiency
Hydroxyglutaric aciduria
Isovaleric acidemia
Maple syrup urine disease
Methylmalonic acidemia
Propionic acidemia types I, II
β-Ketothiolase deficiency
Urea cycle defects and disorders of ammonia detoxification
Urea cycle defects
Argininemia
Argininosuccinic aciduria
Carbamoyl phosphate synthetase deficiency
Citrullinemia
N-acetyl glutamate synthetase deficiency
Ornithine transcarbamylase deficiency

Hepatic amino acid transport
Homocitrullinuria, hyperornithinemia, and hyperammonemia (HHH) syndrome
Lysinuric protein intolerance
Fatty acid oxidation defects
Carnitine palmitoyltransferase deficiency types I, II
Carnitine transporter deficiency
Carnitine-acylcarnitine translocase deficiency
Hydroxymethylglutaryl-CoA (HMG-CoA) lyase deficiency, HMG-CoA synthetase deficiency
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
Medium-chain 3-ketoacyl thiolase (MCKAT) deficiency
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
Short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency


Disorders of carbohydrate metabolism
Carbohydrate intolerance disorders
Galactosemia
Galactokinase deficiency
Hereditary fructose intolerance
Fructosuria
Fructose-1,6-diphosphatase deficiency
Carbohydrate production/utilization disorders
Glycogen storage disorder types 0, Ia (von Gierke), Ib/c, Ic, II (Pompe), IIb, III (Cori or Forbes), IV
(Anderson), V (McArdle), VI (Hers), VII (Tarui), VIII, IX, X, XI
Lysosomal storage disorders
Mucopolysaccharidosis (MPS)
MPS IH (Hurler), IH/S (Hurler–Scheie), IS (Scheie), MSII (Hunter), IIIA–D (Sanfilippo), IVA, B
(Morquio), VI (Maroteaux–Lamy), VII (Sly)

Sphingolipidoses
Canavan disease
Fabry disease
Farber disease
Gaucher disease types I–III
GM1 gangliosidosis types 1–3
GM2 gangliosidosis types 1 (Tay–Sachs), 2 (Sandhoff)
GM3 gangliosidosis
Krabbe disease
Metachromatic leukodystrophy—infantile, juvenile, adult
Multiple sulfatase deficiency
Niemann–Pick disease—types IS, IC, IIA, IIS, IIC
Oligosaccharidoses (glycoproteinoses)
Aspartylglucosaminuria
Fucosidosis types I, II
Galactosialidosis
Mannosidosis α types I, II, β
Pycnodysostosis (Maroteaux–Lamy III)
Schindler disease
Sialidosis types I, II (previously mucolipidosis I)
Sialolipidosis
Mucolipidosis
Mucolipidosis types II (I-cell), III (pseudo-Hurler), IV
Mitochondrial disorders
2-Ketoglutarate dehydrogenase complex deficiency
Friedreich ataxia
Fumarase deficiency
Glutaric acidemia type II
Kearns–Sayre syndrome
Leigh disease

Mitochondrial encephalomyopathy lactic acidosis stroke-like episodes
Myoclonic epilepsy, ragged red fiber disease
Pearson syndrome


Phosphoenolpyruvate carboxylase deficiency
Pyruvate carboxylase deficiency
Pyruvate dehydrogenase complex deficiency
Succinate dehydrogenase deficiency
Peroxisomal disorders
Adrenomyeloneuropathy
Adrenoleukodystrophy in neonatal, adult
Catalase deficiency
Glutaric acidemia type III
Leber hereditary optic neuropathy
Refsum disease infantile, adult
Rhizomelic chondrodysplasia punctata
Wolfram syndrome
Zellweger syndrome
Congenital disorders of glycosylation
Disorders of metal transport
Disorders of heme metabolism
Disorders of nucleic acid metabolism
Disorders of cholesterol synthesis
Disorders of bile acid synthesis
Disorders of neurotransmitter metabolism
Laboratory Findings. In the patient with potentially life-threatening symptoms, evaluation for possible
IEM should be initiated immediately.
The initial laboratory evaluation of a patient with suspected IEM includes electrolytes, glucose, venous
blood gas, CBC, ammonia, lactate, blood urea nitrogen (BUN), creatinine, liver tests (aspartate

transaminase [AST] and alanine transaminase [ALT], prothrombin time [PT], partial thromboplastin time
[PTT]), uric acid and urinalysis. If possible, the initial evaluation should also include samples for
specialized testing including plasma amino acids, urine organic acids, and acylcarnitine profile ( Table
95.4 ). In addition to these studies, patients with history or physical examination suggestive of myopathy
should have lactate dehydrogenase, aldolase, creatinine phosphokinase, and urine myoglobin measured as
part of their initial screen.
If a metabolic disease is suspected, consultation with an IEM specialist should be considered to guide
further laboratory evaluation and assist with the appropriate collection and processing of specimens.
Blood should be collected and sent for plasma amino acids and acylcarnitine profile, while urine should
be collected for potential analysis of organic acids, acylglycine, and/or orotic acid ( Table 95.5 ).
Additional blood and urine for possible further testing should be obtained and stored. Cerebrospinal fluid
(CSF), if obtained, should be collected at the same time as plasma and immediately frozen and stored for
possible further testing for neurometabolic disorders, most commonly nonketotic hyperglycinemia,
disorders of serine biosynthesis, and/or neurotransmitter disorders. Measurement of lactate and pyruvate
are important components of the ED evaluation but may be difficult to interpret, particularly in the patient
with hypoxia, poor perfusion, seizure, and/or sepsis. Laboratory abnormalities are often transient,
particularly if fluids and/or glucose are administered; therefore, normal values do not rule out an IEM. It
is critical to obtain pretreatment specimens, if possible. If pretreatment specimens were not obtained, as is
often the case because many IEMs are first suspected based on results of routine laboratory studies,


discarded pretreatment samples are likely to be more informative than those collected after therapy.
Collection of samples during acute illness is usually preferred to provocative testing by metabolic
challenge performed when the child is otherwise well because this method may not yield diagnostic
specimens and may be dangerous.
The confirmatory specific diagnosis of most IEMs requires additional specialized testing for abnormal
metabolites, perturbed enzymatic function, or molecular testing.
When a child dies in the ED and an IEM is suspected, it is extremely important to attempt to diagnose
that disease because of the possibility that asymptomatic family members are affected or future children
are at risk. Routine autopsy does not usually provide a definitive diagnosis of IEM but may rule out other

causes of death and offer clues. IEMs can be diagnosed in the child who has just died by collecting the
appropriate specimens ( Table 95.6 ). In some situations, exome sequencing, genome sequencing, or
metabolomics may be used to evaluate for an underlying cause of decompensation. This evaluation is
usually guided by specialty consultation. Most IEMs can be categorized based on findings of initial
laboratory evaluations. Nearly all patients with IEMs that present as acute life-threatening disease will
have hypoglycemia, metabolic acidosis, and/or hyperammonemia. These initial findings will guide
immediate treatment and further evaluation. Important exceptions are nonketotic hyperglycinemia
(usually presents within 48 hours of birth with lethargy, coma, seizures, hypotonia, spasticity, hiccups,
and apnea) and pyridoxine deficiency and folinic acid–responsive disorders (which present with
intractable seizures with or without encephalopathy as neonate).