• Clinical science

Inborn errors of metabolism


Inborn errors of metabolism are a group of inherited disorders characterized by enzyme defects. Clinical manifestations are usually due to the accumulation of toxic substances in the body. While in many cases the disorder cannot be cured, disease outcomes and life expectancy can be improved with supportive care and the appropriate diet.

Alpha-1 antitrypsin deficiency (AAT deficiency)

The diagnosis of alpha-1 antitrypsin deficiency should be considered in all patients with emphysema under the age of 50.

References: [9][7][8][6][5][4][2][6][3][1]

Mitochondrial myopathies

General considerations

Subtypes of mitochondrial myopathies [10]


Disorders of amino acid metabolism

Alkaptonuria [20][21]

Homocystinuria [22]

Marfan syndrome and homocystinuria both present with marfanoid habitus. Distinguishing features include intellectual disability, which is only seen in homocystinuria, and the direction of lens dislocation (downwards in homocystinuria; upwards in Marfan syndrome).

Remember HOMOCYstinuria: Homocystinuria, Osteoporosis, Marfanoid habitus, Ocular changes (lens subluxation), Cardiovascular (thromboembolism, accelerated atherosclerosis), kYphosis.

Hartnup disease [22][26]

Phenylketonuria (PKU) [27][28][29][30]

Patients with PKU should be advised to avoid aspartame, an artificial sweetener that contains phenylalanine!

Cystinuria [33]

Maple syrup urine disease [22][34][35][36]

Mnemonic for amino acids involved in maple syrup urine disease: I Love Vermont maple syrup from maple trees (with branches) → I = Isoleucine, Love = Leucine, Vermont = Valine, branches = branched-chain amino-acids

Pyruvate dehydrogenase complex deficiency [22][37]

Propionic acidemia [38][39]

References: [21][25][23][24][26][40][41][34][36][37][38][39]

Purine salvage deficiencies

Lesch-Nyhan syndrome [42][22][43]

To remember the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which is involved in Lesch-Nyhan syndrome: He's Got Purine Recovery Troubles OR Hyperuricemia, Gout, Pissed off (aggression, self-mutilation), Retardation (ID), DysTonia!

Adenosine deaminase deficiency [44]


Disorders of fatty acid metabolism

Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency) [45][46]

References:[47] [46]

Primary carnitine deficiency [46][22]

Carnitine palmitoyltransferase II deficiency (CPT II deficiency) [48][49][50]

Urea cycle disorders

Ornithine transcarbamylase deficiency (OTC deficiency) [51][52][53]

OTC deficiency is the only urea cycle disorder that is X-linked recesssive. All of the other urea cycle disorders are autosomal recessive.

Arginase deficiency [51][54]

References:[55][52][54] [51]

Orotic aciduria

Orotic aciduria can be distinguished from ornithine transcarbamylase deficiency by the presence of megaloblastic anemia and absence of hyperammonemia!