Genetic Brain Disorders

Inborn Errors of Metabolism

The study of genetic brain disorders was largely established when Archibald Garrod published Inborn Errors of Metabolism in 1923. Inborn errors of metabolism are uncommon individually, but occur quite frequently when taken as a whole. Collectively, there is approximately 1 in 1,400 to 1 in 5,000 disorders per live birth. The incidence among different racial and ethnic groups varies among the diseases. They are often due to defective genes that regulate enzymes or transport proteins. These diseases can be divided into the following categories: carbohydrate metabolism, amino acid metabolism, organic acidemias, lysosomal storage diseases, fatty acid metabolism, and mitochondrial disorders. Most of these disorders are of autosomal recessive inheritance. The presentation of the disease can vary even within each specific disease type, ranging from differing ages of onset to variable levels of clinical severity.

Various types of inherited disorders will result in differing mental deficits. For example, the psychoses and hallucinations may be due to any of the following disorders: lysosomal defects (Sanfilippo and Hunter diseases, GM2 gangliosidosis, neuronal ceroid lipofuscinosis, Krabbe disease), purine metabolism defects (Lesch-Nyhan syndrome), peroximsomal defects (adrenoleukodystrophy), Wilson's disease, acute intermittent porphyria, and homocystinuria. Developmental delay may also result from metabolic defects such as lysosomal defects, disorders of amino acids, organic acids, carbohydrates, copper metabolism (Menke's disease, Wilson's disease), and peroxisomes (adrenoleukodystrophy, Zellweger syndrome). Seizures and ataxias can manifest secondary to metabolic diseases.

It is important to diagnose and treat patients with inborn errors of metabolism because a delay in either may lead to long-term neurologic impairment. Patients should also be referred to appropriate counseling, as there exist many profession and peer support groups for individuals with these disorders. Genetic counseling should also be offered to evaluate recurrence risks, familial screening, and prognosis.

Hereditary Movement Disorders

Hereditary movement disorders may include neurologic deficits such as ataxia, dystonia, and chorea. Ataxia is the inability to maintain posture or smooth movement. Dystonias are defined as diseases that cause an abnormal muscle tone, while choreas are diseases associated with involuntary spastic movements. The differences in disorders are largely due to the gene and location of the gene deficits. The spinocerebellar pathways are involved in the majority of hereditary ataxia syndromes. These disorders can be associated with three different types of mutations.

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