• 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 AAT deficiency should be considered in all patients with emphysema under the age of 50 years.

Mitochondrial myopathies

General considerations [10]

Subtypes of mitochondrial myopathies [10][11][12]

Disorders of amino acid metabolism

Phenylketonuria (PKU) [20][21][22]

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


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 and upwards in Marfan syndrome).

The most important features of homocystinuria are Marfanoid habitus, skeletal abnormalities (e.g., osteoporosis, kyphosis), accelerated atherosclerosis, and downward lens subluxation: “Tall grown, brittle bone, vessels of stone, lens in downward zone.”

Hartnup disease [30]

Alkaptonuria [32][33]

Maple syrup urine disease [35][36][37]

Grab the Maple BRANCH if you want to LIVe! In Maple syrup urine disease, the breakdown of BRANCHED amino acids (Leucine, Isoleucine, and Valine) is impaired.

Cystinuria [39]

To remember the four dibasic amino acids that cannot be absorbed by the kidney in cystinuria, think of “Dibasic COAL: Cystine, Ornithine, Arginine, Lysine.”

Organic acidemias [40][41][42]

Infants PRObably VOMIT when affected by organic acidemia: in PROpionic acidemia, Valine, Odd-chain fatty acids, Methionine, Isoleucine, and Threonine should be avoided.

Cystinosis [43][44]

Histidinemia [45][46]

Pyruvate dehydrogenase complex deficiency

Purine salvage deficiencies

Lesch-Nyhan syndrome [48][49]

To remember the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which is involved in Lesch-Nyhan syndrome: He's Got Purine Recovery Troubles OR Hyperuricemia, Gout, Poor intellect, Rage/aggression, abnormal muscle Tone.

Adenosine deaminase deficiency [50]

Disorders of fatty acid metabolism

Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency) [51][52][53]

Primary carnitine deficiency [53]

Carnitine palmitoyltransferase II deficiency (CPT II deficiency) [54][55][56]