Academic journal article International Journal of Child and Adolescent Health

Adolescence and Metabolic Disorders

Academic journal article International Journal of Child and Adolescent Health

Adolescence and Metabolic Disorders

Article excerpt


Inborn errors of metabolism (IEMs) or metabolic disorders are unusual, complex conditions involving abnormalities in biochemical and metabolic pathways necessary for human life. Though often identified in infancy or childhood, some may not be diagnosed until adolescence or adulthood. The initial term, inborn errors of metabolism, was introduced by Sir Archibald Garrod in 1902 and referred to cystinuria, albinism, alkaptonuria, and benign pentosuria (1). Phenylketonuria (PKU) was identified in 1934 by Ivar Asbjørn Følling (1888-1973) and in the second half of the 20st century, over 500 IEMs have been identified (2). Table 1 presents a partial list of IEMs (2).

IEMs are complex conditions that are usually genetic, typically inherited in an autosomal recessive manner, though a few are X-linked recessive conditions (i.e., Fabry disease, ornithine carbamylase deficiency, or pyruvate dehydrogenase deficiency). Autosomal dominance is noted in Marfan syndrome, familial hypercholesterolemia, and acute intermittent porphyria. Some IEMs are caused by mitochondrial genome mutations and there can be enzyme deficiencies or problems with cellular transporters.


The incidence of IEMs varies to a considerable extent depending on the specific condition. For example, congenital hypothyroidism is noted in 1:4,500, congenital adrenal hyperplasia in 1:10,000, medium chain acyl CoA dehydrogenase (MCAD), phenylketonuria in 1:15,000, and galactosemia in 1:30,000. A number of IEMs are much rarer and noted in 1:100,000-such as fatty acid oxidation disorders, organic acidemias, homocystinuria, maple syrup urine disease (MSUD), and others (2). Some IEMs are seen in increased incidence among certain populations such as Tay Sachs in the Ashkenazi Jewish population or maple syrup urine disease (MSUD) in United States Pennsylvania Mennonites. Consanguinity is a factor in some of these conditions.


IEMs may present with metabolic syndromes (acute acidotic or hypoglycemia crises), hepatic syndromes (liver disease with abnormal liver function tests), cardiac syndromes (acute cardiac myopathy or cardiovascular collapse), or neurological syndromes (altered mental status or neurological functioning). The neurological syndromes can have acute or chronic presentations and involve seizures, sensory dysfunctions, coma, changes of tone, intellectual deterioration, behavioral dysfunction, psychosis, and others. In the metabolic presentations, there can be acidosis, hypoglycemia, or hyperammonemia (i.e., urea cycle defects). There can also be progressive, chronic cellular storage disorders with variable presentations.

Some can present later on in childhood, such as metachromatic leukodystrophy, Tay-Sachs disease, Gaucher's disease, lysosomal storage disorders, and others (2). There can be progressive neurological deterioration and some conditions result in mental subnormality that have an onset in adolescence or adulthood (Table 2) (3). A wide variety of features can be seen including dysmorphic phenotypes as well as abnormalities in different organ systems, such as gastrointestinal, dermatological, hematological, and others.

Unique odors can be present such as burnt sugar or maple syrup -like in MSUD, fruity odor in acidemias (propionic or methylmalonic), mousy (musty) in PKU, cheese-like (sweaty socks) in isovaleric academia, malt-like in methionine malabsorption, fish-like in trimethylaminuria or carnitine excess, cat urine-like (3-methylcrotonic academia or 3-hydroxy- 3-methyl glutaric aciduria) or cabbage-like in tyrosinemia (2).

Thus, a careful evaluation along with a high index of clinical suspicion is necessary to make the correct diagnosis, often in consultations with experts in genetics, metabolic disorders, and other specialists. The diagnosis may be delayed for many years if the presentation of the condition is non-specific or mild often due to a partial enzyme deficiency. …

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