The correct diagnosis of inherited metabolic diseases that affect the nervous system primarily is a major challenge because the same neurological symptoms and often even disease course may be caused by non-metabolic disorders.
Neurometabolic diseases often start with common and non-specific signs, such as isolated developmental delay/mental retardation, seizures, dystonia, or ataxia. They are especially to be suspected when the course of the disease is progressive or when additional neurological systems or other organs become involved. An important clue is the co-existence of different neurological features that cannot be explained by a “simple” neuroanatomic approach.
Acute or recurrent attacks of neurological manifestations such as coma, ataxia or abnormal behaviour are major presenting features especially in the late-onset inborn errors of metabolism (see also B2.7).
The initial diagnostic approach to these disorders is based on a few metabolic screening tests. It is important that the biologic fluids are collected at the time of the acute attack. And always consider treatable disorders first when choosing your plan of investigations.
Metabolic investigations are usually not indicated in children with moderate static developmental delay, isolated delay of speech development in early childhood, occasional seizures, e.g. during fever, or well-defined epileptic syndromes. Other genetic aetiologies outside the metabolic field have also been considered, especially as causes of mental retardation, ataxia, dystonia, and spastic paraplegia.
KeywordsInborn Error Mitochondrial Disorder Neuronal Ceroid Lipofuscinoses Glutaric Aciduria Type Biotinidase Deficiency
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