Diagnosis is the very core of clinical medicine – this is why people bother to come to see you. And if one misses the diagnosis of a treatable condition, one has messed up. Which is easy to do – as Rarity is about context (things that are rare in one context are common in another) and it’ about how you define rare (1:200, 1:10,00, etc). However you look at it, there are around 350 million people in the world with a rare disease; and for children affected by these conditions, 1 in 3 will die before the age of 5 years.
Lysosomal storage disorders are inherited deficiencies of metabolic enzymes which are examples of rare multi-system diseases which have a large variety of clinical presentations. Although many present in childhood, and there will often be a family history, many present to adult physicians and since most are autosomal recessive, most sufferers do not have a family history. Symptoms are often non – specific (eg fatigue; failure to thrive or growth failure in children) but some of the features can be quite specific eg hepatosplenomegaly, left ventricular enlargement, renal failure, cataract, hearing loss, stroke. There is scope for developing targeted screening approaches to improve diagnosis rates in high risk groups. Neonatal screening is increasingly used but yields few individuals with significant manifestations and many individuals with non pathogenic mutations are found.
I work at a Centre for these disorders in London. Most of the patients we see have had to endure a delay in diagnosis. Patients are referred by a range of physicians – haematologists, nephrologists, cardiologists, neurologists, pediatricians and even surgeons. About half of our patients are diagnosed through pedigree analysis. I will talk about how to diagnose – and not to miss – Gaucher disease and Fabry disease.