Academic journal article International Journal of Child Health and Human Development

Inborn Errors of Metabolism, Psychiatry and Dermatology

Academic journal article International Journal of Child Health and Human Development

Inborn Errors of Metabolism, Psychiatry and Dermatology

Article excerpt


Inborn errors of metabolism (IEMs) comprise a wide range of heritable disorders, most of which are autosomal recessive. Many of these have a high rate of morbidity and mortality if undiagnosed or diagnosed late. However, early diagnosis and timely institution of appropriate interventions may result in significant clinical improvement. Many of these defects are therefore screened for on newborn screening programs (NBS).

IEMs may involve any of the physiologic, biochemical, and metabolic pathways characterized by developmental delays, neuropsychiatric manifestations, and typical cutaneous features. Inborn errors of metabolisms (IEM) are relatively rare but often overlooked underlying causes of psychiatric presentations in children and adolescents. Psychiatric conditions may manifest much earlier and often may be the only type of presenting symptoms, predating the presentation of symptoms related to other systems sometimes by many years (1). The psychiatric and cognitive symptoms seen in IEM are of wide variety and range from vague nonspecific symptoms to severe psychosis and delirium. Some of these disorders are discussed in more detail with respect to their psychodermatologic aspects in this review. See table 1 as well as figures 1 and 2.

Phenylketonuria [PKU]

Phenylketonuria (PKU) is also called Følling disease, phenylalanine hydroxylase deficiency, hyper-phenylalaninemia, and OMIM # 261600. PKU was the first clearly delineated inborn error of metabolism, and has been on the newborn screen (NBS) program in the United States since the 1960s. In fact the NBS has been referred to as the" PKU screen". The diagnostic testing was first implemented by Guthrie (3). The incidence of PKU varies greatly in different countries and ethnicities; overall, the incidence in the Caucasian population is about 1: 11,000 and 1:50,000 in the African Americans. Males and females are affected equally (4).

Genetics and pathophysiology

PKU is an autosomal recessive metabolic disorder of the metabolism of the amino acid phenylalanine. The defect is a mutation in the phenylalanine hydroxylase gene resulting in accumulation of phenylalanine.

Clinical features

The clinical features seen in PKU are the result of accumulation of phenylalanine. Neonates are born normal and as the levels of phenylalanine start accumulating, the clinical features are noted progressively after the first few weeks/months of life. Newborns may present with typical symptomatology if the mother herself has PKU and was poorly controlled during pregnancy.

Clinical hallmarks of the disease include the following (4, 5):

· Neurological features consisting of mental retardation, seizures, and microcephaly are significant. There may be irritability, hyperactivity, and self-destructive behavior as well.

· Features include excessive heavy vomiting, growth failure, and failure to thrive. A mousy odor is noted in the sweat and urine secondary to the accumulation of phenylacetic acid.

Cutaneous manifestations

The typical cutaneous manifestations include eczema, hypopigmentation, and photosensitivity. The eczema develops early in infancy, is seen in 20-50% of infants in the 1st year of life, and progressive worsening is noted (4). The eczema and seborrheic dermatitis that is seen is essentially the same as that seen in atopic dermatitis and is reversible on a low phenylalanine diet.

The other very striking feature of PKU is hypopigmentation of the skin and appendages including pale skin, blue eyes, and blond hair seen in a majority of the PKU patients (4 ,6). This is believed to be caused by inhibition of tyrosinase enzyme which decreases melanin formation. Patients also exhibit significant photosensitivity. Edematous, scleroderma-like changes develop in the extremities and characteristically do not involve the hands and feet (7, 8). Segmental sclerosis and atrophoderma of Pasini and Pierini has been reported in PKU (9). …

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