Inborn Errors of Metabolism

Introduction

  Hypoglycemia can be an inborn error of metabolism that adversely affects the brain. However, it can also have other causes such as starvation, pancreatic cancer, etc. In pancreatic cancer the pancreas can secrete too much insulin. In any case psychiatric symptoms are seen. Adelle Davis and others have used this as a biochemical model for mental illness. The Harris diet is used as a treatment. Both Davis and Harris are deceased, unfortunately. 

"Specific and effective treatment is possible for many inborn errors due to advances in the understanding of their biochemical basis. Early clinical diagnosis is essential in ensuring that the affected infants will be benefited by these advances."

Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Post box 2900, Bangalore-560 029, India

¹Department of Neurology, National Institute of Mental Health and Neuro Sciences, Post box 2900, Bangalore-560 029, India

For correspondence: Rita Christopher, Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Post Box 2900, Bangalore-560 029, India. E-mail: rita@nimhans.kar.nic.in

  This quote is from Ref. 1, which is an open-access article. This means that it can be quoted at will if the proper citation is given.

Inborn Errors

  Ref. 2 is the first book that I know of written on inborn errors of metabolism. Ref. 3 is a more recent book, which covers far more errors. Ref. 4 describes an error that is delayed in onset. Huntington's chorea is another inherited disease that has a delayed onset. The disease is dormant until adulthood.

  Refs. 4 & 5 describe diseases with behavioral abnormalities. This is also seen in Huntington's chorea, MELAS, and PKU. PKU is an amino acid abnormality where a very strict low protein diet is used as a treatment.

  There is a theory that schizophrenia is inherited. This point of view was favored by the late Linus Pauling. Many mental illnesses may be hereditary.

Amino Acids

  Inborn errors of metabolism involving amino acids are notorious for producing psychiatric symtoms. One disease in this category is PKU. Linus Pauling pointed this out in his 1968 paper in Science called "Orthomolecular Psychiatry". The disease is treated by a diet low in the amino acid phenylalanine. The disease can produce brain pathology. Excessive amounts of phenylalanine poison the brain.

  There are other inborn errors of metabolism involving amino acids. Acute intermittent porphyria, which has a late onset, involves an excess of tryptophan in the brain due to the lack of an enzyme. This disease presents with anxiety, depression, paranoia, and restlessness. It is treated with heme. For more information on this, consult Ref. 6.

  Urea cycle disorders present with the symptoms of periodic acute agitation, hallucination, and anxiety (6). The plasma ammonia is up. The plasma amino acids are abnormal. This is another late onset disorder.

Late-Onset Disorders

"In many late-onset neurometabolic disorders, the first indication of the onset of disease may be behavioral or personality changes." (1)

  Late-onset metachromatic leukodystrophy presents with symtoms of anxiety, emotional lability, disorganized thinking, poor memory, and psychosis. Wilson's disease presents with symptoms of anxiety, depression, mania schizophrenia, and antisocial behavior.

Conclusions

  Although some of these diseases are rare, there are so many of them that they are important. They provide massive evidence that psychiatric problems are organic. Mental retardation can be seen in some disorders including PKU.

  Refs. 7-9 discuss psychiatric symptoms and problems including treatments. The treatments themselves can cause problems if drugs are used. 

References

1. An insight into the biochemistry of inborn errors of metabolism for a clinical neurologist. Rita Christopher and Bindu P. SankaranAnn Indian Acad Neurol. 2008 Apr–Jun; 11(2): 68–81. doi: 10.4103/0972-2327.41873.

2. Garrod AG. Inborn error of metabolism. Oxford: Oxford University Press; 1909.

3. Scriver CR, Beaud, Sly WS, Valle D, et al., editors. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001.

4. Joseph KA, Van ger pen MW, Van Gerpen JA. Adult onset Nieman-Pick disease type C presenting with psychosis. J Neurol Neurosurg Psychiatry. 2003;74:528–9.

5. Dimango EP, Lowe JE, Snodgrass PJ, Jones JD. Ornithine carbamylase deficiency: A cause of bizarre behaviour in a man. N Engl J Med. 1986;315:744–7.

6. Clarke JT, editor. A clinical guide to inherited metabolic diseases. 2nd ed. United Kingdom: Cambridge University Press; 2002.

7. www.associatedcontent.com/article/2390658/insomnia_its_causes_and_treatments.html
8. www.associatedcontent.com/article/2371816/anxiety_causes_and_treatment.html

9. http://www.associatedcontent.com/article/261514/drug_abuse.html