Amino acid catabolism disorders are caused by a genetic deficiency of one of the enzymes involved in the degradation of some amino acid(s). In other words, from the moment of birth, one of these enzymes is defective and causes a “metabolic block”.
There are mild forms of these diseases in which the enzyme is somewhat functional, but not enough to break down the corresponding amino acid (or its derivative) properly. This is a “partial deficiency” with “residual enzyme activity”.
Consequences of enzyme deficiencies
The existence of a metabolic block at some point of the metabolic pathway leads to (Fig. 2):
- accumulation of substances (amino acid(s) or derivatives) upstream from the enzyme deficiency;
- and defective production of substances downstream from the enzyme deficiency.
The accumulation of substances upstream from the metabolic block is the main cause of the signs of the disease. In great quantities, these substances are “toxic” to the body.
This is a disease due to “toxicity”. Depending on the substance involved, there are disorders of amino acid metabolism, in which the toxic substance involved is one or more amino acids (e.g. phenylketonuria or maple syrup urine disease) and organic acidurias or acidaemias, in which the toxic substance involved is an organic acid, which is an intermediate product of the breakdown of an amino acid (e.g. methylmalonic aciduria or propionic aciduria).
Toxicity can be chronic (with progressive signs that evolve gradually) or acute (sudden, due to acute decompensation of the disease). Both situations can coexist when an acute decompensation occurs in a context of chronic toxicity. It is worth noting that phenylketonuria differs from other disorders in this category in that it does not cause acute decompensation, only chronic toxicity.
Your child’s gastrointestinal system and digestion are normal.
Transmission of the disease
These are autosomal recessive hereditary genetic disorders (usually inherited from both parents). This means the “anomalous” gene is “hidden” in the chromosomes of both parents and, therefore, your child has two copies of it. This is when the disease manifests. People (like you, the parents) who carry the anomalous gene in just one of the two chromosomes will remain free of the disease throughout their lifetimes; you are known as “healthy carriers”.
The risk of having a child with the disorder is 1 in 4 (i.e. 3 in 4 probability that the child is healthy) for each pregnancy (Fig. 3). In rare cases, the genetic anomaly in one of the two chromosome appears spontaneously in the child (“de novo” mutation), and the anomalous gene is only present in one of the two parents.
The prevalence of these diseases varies from one to the other, but they are very rare diseases and recognised as such: “RARE DISEASES” or orphan diseases.
These are congenital diseases; in other words, they are present at birth and throughout the life of your child, and they are part and parcel of your child.
There is no cure for these diseases at present.
It needs to be understood in order to be able to:
- integrate it;
- apply it every single day;
- explain it to your child at the earliest age possible to help him or her understand it and become autonomous.