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Inborn errors of metabolism

Last updated: January 13, 2021

Summarytoggle arrow icon

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.

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

General considerations [10]

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

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]

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]

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]

Ornithine transcarbamylase deficiency (OTC deficiency) [57][58][59]

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

Arginase deficiency [57][60]

  • Definition: congenital disorder characterized by impaired arginase activity, resulting in the accumulation of nitrogen (in the form of ammonia)
  • Inheritance: autosomal recessive
  • Pathophysiology: absent or nonfunctional arginase enzyme impaired conversion of arginine to ornithine accumulation of ammonia and arginine in the serum
  • Clinical features
  • Diagnostics
  • Treatment
    • Reduce serum ammonia
      • Nitrogen scavengers such as sodium phenylacetate and sodium benzoate
      • Fluid management
      • Dialysis (in severe cases)
    • Low-protein diet

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

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