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The discovery of a leukoencephalopathy is a frequent situation in neurological practice and the diagnostic approach is often difficult given the numerous possible aetiologies, which include multiple acquired causes and genetic diseases including inborn errors of metabolism (IEMs). It is now clear that IEMs can have their clinical onset from early infancy until late adulthood. These diseases are particularly important to recognize because specific treatments often exist. In this review, illustrated by personal observations, we give an overview of late-onset leukoencephalopathies caused by IEMs.

Inborn errors of metabolism (IEMs) represent poorly known causes of epilepsy in adulthood. Although rare, these are important to recognize for several reasons: some IEMs respond to specific treatments, some antiepileptic drugs interfering with metabolic pathways may worsen the clinical condition, and specific genetic counselling can be provided. We review IEMs potentially revealed by epilepsy that can be encountered in an adult neurology department. We distinguished progressive myoclonic epilepsies (observed in some lysosomal storage diseases, respiratory chain disorders and Lafora disease), from other forms of epilepsies (observed in disorders of intermediary metabolism, including porphyrias, creatine metabolism defects, glucose transporter (GLUT-1) deficiency, Wilson disease or succinic semialdehyde dehydrogenase deficiency). We propose a diagnostic approach and point out clinical, radiological and electrophysiological features that suggest an IEM in an epileptic patient.

Spastic paraparesis is a general term describing progressive stiffness and weakness in the lower limbs caused by pyramidal tract lesions. This clinical situation is frequently encountered in adult neurology. The diagnostic survey is usually limited to searching for acquired causes (spinal cord compression, inflammatory, metabolic, infectious diseases) and the so-called 'hereditary spastic paraparesis'. Although poorly recognized by neurologists, spastic paraparesis is also one of the multiple presentations of inborn errors of metabolism (IEMs) in children and adults. Pyramidal signs are usually included in a diffuse neurological or systemic clinical picture; however, in some cases spastic paraparesis remains the only symptom for years. Since these metabolic causes are often treatable, it is essential to include them in the general diagnostic approach to spastic paraparesis. Here we review IEMs causing paraparesis in adults.

Inborn errors of metabolism (IEMs) may present in adolescence or adulthood as a psychiatric disorder. In some instances, an IEM is suspected because of informative family history or because psychiatric symptoms form part of a more diffuse clinical picture with systemic, cognitive or motor neurological signs. However, in some cases, psychiatric signs may be apparently isolated. We propose a schematic classification of IEMs into three groups according to the type of psychiatric signs at onset. Group 1 represents emergencies, in which disorders can present with acute and recurrent attacks of confusion, sometimes misdiagnosed as acute psychosis. Diseases in this group include urea cycle defects, homocysteine remethylation defects and porphyrias. Group 2 includes diseases with chronic psychiatric symptoms arising in adolescence or adulthood. Catatonia, visual hallucinations, and aggravation with treatments are often observed. This group includes homocystinurias, Wilson disease, adrenoleukodystrophy and some lysosomal disorders. Group 3 is characterized by mild mental retardation and late-onset behavioural or personality changes. This includes homocystinurias, cerebrotendinous xanthomatosis, nonketotic hyperglycinaemia, monoamine oxidase A deficiency, succinic semialdehyde dehydrogenase deficiency, creatine transporter deficiency, and alpha and beta mannosidosis. Because specific treatments should be more effective at the 'psychiatric stage' before the occurrence of irreversible neurological lesions, clinicians should be aware of atypical psychiatric symptoms or subtle organic signs that are suggestive of an IEM. Here we present an overview of IEMs potentially revealed by psychiatric problems in adolescence or adulthood and provide a diagnostic strategy to guide metabolic investigations.

Although they are classically viewed as paediatric diseases, it is now recognized that inborn errors of metabolism (IEMs) can present at any age from childhood to adulthood. IEMs can involve the peripheral nervous system, mostly as part of a more diffuse neurological or systemic clinical picture. However, in some cases, the neuropathy can be the unique initial sign. Here, based on our personal experience and on a comprehensive literature analysis, we review IEMs causing neuropathies in adults. Diseases were classified according to the predominant type of neuropathies into (1) acute neuropathies, (2) mononeuropathy multiplex, (3) chronic axonal polyneuropathies, (4) chronic demyelinating polyneuropathies, (5) small-fibre neuropathies, and (6) lower motor neuron disease.