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When to suspect inherited metabolic diseases
  1. Samuel Shribman1,2,
  2. Robin H Lachmann1
  1. 1Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK
  2. 2Atkinson Morley Regional Neuroscience Centre, St George's University Hospitals NHS Foundation Trust, London, UK
  1. Correspondence to Dr Samuel Shribman, Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK; s.shribman{at}

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Neurologists sometimes experience a nagging feeling that they might be missing something treatable. Reluctantly, they may ask themselves ‘could it be metabolic?’ in the knowledge that there is a plethora of inherited metabolic diseases, many of which they have not encountered and/or which require highly specialised biochemical investigations or treatments, such as complex diets.

In this edition of Practical Neurology, Finezilber et al describe a young adult with a generalised myopathy associated with developmental delay, short stature and dysmorphic features caused by arginine:glycine amidinotransferase deficiency, a disorder of creatine metabolism.1 The diagnosis was made through genome analysis followed by confirmatory biochemical testing. There was a dramatic improvement in motor function with creatine supplementation. The case highlights several important points about the diagnosis of metabolic disorders more broadly, including the potential for diagnostic delays, and leads us to explore when neurologists should suspect inherited metabolic diseases, with reference to some specific examples than can present in adulthood.

Neurometabolic disorders can present as an acute crisis or as a chronic, neurodegenerative process.2 Encephalopathy can develop with the accumulation of toxic molecules such as ammonia (urea cycle disorders, organic acidurias), certain amino acids (maple syrup urine disease, non-ketotic hyperglycinaemia) or their breakdown products (organic acidurias). Inherited metabolic diseases can also present acutely with lacunar stroke (Fabry disease), venous sinus thrombosis (classical homocystinuria) or rhabdomyolysis (fatty acid oxidation disorders and glycogen storage disorders). Insidious presentations with neuromuscular, movement and/or cognitive disorders typically occur with complex …

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  • Contributors SS and RHL drafted the manuscript and approved the final version. SS is guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally reviewed by Jon Walters, Swansea, UK.

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