'THANKS TO NEONATAL SCREENING AND EARLY DETECTION THE SEQUELAE THAT WOULD RESULT FROM DELAYED DIAGNOSIS OF METABOLOPATHIES ARE AVOIDED"
Mar 2, 2021
For Dr. Isidro Vitoria, paediatrician and biochemist in charge of the Nutrition and Metabolopathies Unit of the University Hospital La Fe, "it is very important to highlight metabolopathies, a significant percentage of rare diseases". Specialised in paediatric nutrition, he has written educational books, has a blog and gives talks so we can understand what metabolopathies are and how to help the families. Metabolopathies, first described by Prof. Sir Archilbald Garrod in 1908 as hereditary congenital metabolic diseases, are considered rare, although taken together they involve one of every 600-800 newborns. With early neonatal diagnosis, nutritional and pharmacological treatments have been established that avoid the consequences of the disease. Therefore, in the past 100 years we have learned to treat some serious diseases before they become symptomatic and thus improve the quality of life of patients. Even with an app, too: the La Fe Hospital in Valencia participated in the development of a mobile application called "Intercambios VitaFlo" that help with the diet of patients with metabolic problems.
What are metabolopathies?
Metabolopathies, or innate metabolism errors (IME), are a group of diseases which have in common the presence of a defect in the metabolism of some of the organism's molecules. They can be considered "rare diseases" (fewer than 5 cases for every 10,000 people). Nevertheless, if they are viewed as a group (there are more than 700 distinct diseases) they are much more frequent than is thought. Thus, when we consider the overall frequency, it is estimated at 1 case for every 600-800 people.
How did you specialise in this field?
Many of the metabolopathies have a basic nutritional treatment. The fact of being a paediatrician mostly devoted to childhood nutrition and also being a biochemist, I was inclined to study and treat this type of disease. In this sense, I was lucky to train with Dr. Jaime Dalmau in the Metabolopathies Unit of La Fe University Hospital in Valencia, which he created himself.
How are they detected?
Some are detected from a neonatal screening test by means of the so-called "neonatal heel prick". This is the case with phenylketonuria, glutaric acidemia 1 and beta-oxidation disorders. With early detection the sequelae that could result from delayed diagnosis (neurological and liver problems, above all) are avoided. There is another large group of metabolopathies that continue to be detected by distinct symptoms and for which the prognosis is not always too favourable.
How many types of metabolopathies are there?
Basically, there are two types of metabolopathies. On one side, the metabolopathies of the so-called intermediate metabolism of proteins, carbohydrates and lipids, and for which dietary treatment is fundamental in order to avoid the toxic action of the metabolites. There is another type of metabolopathy called diseases of the cell organelles in which there is a reservoir of complex molecules in different organs and systems.
Do they affect several organs?
Metabolopathies of intermediate metabolism generally affect the brain and, in some cases, the liver as well. Metabolopathies of the cell organelles generally affect different organs and systems such as the heart, lungs, bones, liver, nervous system....
Once diagnosed, how are treatments implemented?
In the case of metabolopathies of the first group, different kinds of food are recommended according to their composition, together with drugs that avoid the accumulation of toxic substances. In the second group, there are lysosomal diseases for which, in recent years, there have been great advances (enzyme substitute treatment, drugs that impede the accumulation of substrate...)
Your work in raising awareness of rare diseases stands out, such as in this lecture, in your blog, on social networks and in books like 'Entendiendo las metabolopatías' (Understanding metabolopathies) where you talk explicitly about these diseases with real cases such as the daughter of the writer Pearl S. Buck.
What happened to her?
Pearl S. Buck had her daughter Carol in 1920 and after just a few months realised that her daughter did not have normal psychomotor development. She relates this in the novel "The child who never grew" (1950) in which she describes the situation. But it was not until 1960 that she knew that her daughter had phenylketonuria, a disease included nowadays in the heel prick as I said earlier, and she would have benefited from early treatment to avoid the psychomotor retardation. Pearl S. Buck not only won the Nobel Prize in Literature, but was a great defender of children with mental disabilities.
You also describe maple syrup urine disease, the one that affects the Amish. What are its causes, and what treatment do they have?
Maple syrup urine disease is called that because the urine smells like that syrup, which is used both in the United States and Canada. Had it been described by a Spaniard it probably would have been called burnt caramel urine disease. It is a metabolopathy of the branch-chained amino acids in which, without dietary and pharmacological treatment, there is serious brain involvement. This illness is very rare in the general population, but among the Amish is much more frequent as a result of sharing the same genetic background and having a higher rate of endogamy.
The La Fe Hospital in Valencia has participated in the development of a mobile application called "Intercambios VitaFlo" to help with the diet of patients with metabolic problems. What does it consist of?
It is an app for patients with specific illnesses (phenylketonuria, tyrosinemia, maple syrup urine disease, organic acidemias, urea cycle disorders and homocystinuria), that allows them to know the amino acid and protein content of the majority of foods. In this way they can make exchanges between foods. This is important to help them in dietary planning as nutritional treatment is basic in these pathologies.
The paediatrician Isidro Vitoria will take part today in the science education series "Una Comunitat amb ciència" with his online lecture "100 years of rare metabolic diseases. What we have learned". The lecture will be presented by Vicente Rubio from the Institute of Biomedicine of Valencia (IBV-CSIC & CIBERER-ISCIII) and member of the Committee of Experts of the Ciutat de les Arts i les Ciències.
Online lecture "100 years of rare metabolic diseases. What we have learned".
For more information about metabolopathies: https://www.metabolicslafe.com/
Photography credits: La Fe Hospital Institute of Health Research