Generality
Maple syrup urine disease (MSUD, from Maple Syrup Urine Disease ) is a rare hereditary disorder that affects the metabolism of certain amino acids .
In detail, the disease is characterized by a defect in the metabolism of branched-chain amino acids (also called BCAAs, from the English Branched Chain Amino Acids ) - leucine, isoleucine and valine - which results in a rather severe symptomatology.
The disease owes its name to the fact that one of the characteristic symptoms is the smell that the urine takes, very similar to that of maple syrup.
What is that
What is Maple Syrup Urine Disease?
Maple syrup urine disease is a rare disease (prevalence of approximately 1 / 185, 000 live births worldwide) also known as leukinosis, branched-chain ketoaciduria or branched-chain ketoacid dehydrogenase deficiency .
It is characterized by the lack of the branched-chain alpha-ketoacid dehydrogenase complex, a complex of multi-subunit enzymes responsible for the metabolism of branched amino acids, such as leucine, isoleucine and valine. This deficiency is due to mutations located in the genes coding for the subunits that make up the aforementioned enzyme. Transmission is autosomal recessive .
The lack of the above enzymatic complex causes the patient to accumulate large amounts of branched amino acids and the corresponding keto acids; condition that can cause serious damage to the body.
The disease manifests itself from the earliest stages of the newborn's life even if, initially, the children with the disease seem healthy.
Causes
What are the Causes of Maple Syrup Urine Disease?
The underlying causes of the onset of maple syrup urine disease lie in genetic mutations located on genes that code for the synthesis of the E1a, E1b and E2 subunits of the branched chain alpha-keto acid dehydrogenase (BCKADC) complex. from the English Branched Chain Keto Acid Dehydrogenase C omplex ). More in detail, the genetic mutations responsible for the disease are found on the BCKDHA (19q13.1-q13.2), BCKDHB (6q14.1) and DBT (1p31) genes.
Manifestations and Symptoms
Clinical manifestations and symptoms of urine syrup in maple syrup
The manifestations and symptoms of the maple syrup urine disease may be slightly different depending on the shape of the patient (see next chapter). However, the onset of the disease can occur in the first days of life of the newborn or within the first two years; in both cases, at birth, the child is apparently healthy.
The characteristic symptom of the disease is the urine smell of the child that resembles that of maple syrup (hence the name of the disease). Other symptoms of the disease are:
- Acute crying;
- Poor appetite;
- Body weight loss;
- Metabolic crisis that can manifest itself with:
- Lack of energy;
- Irritability;
- He retched;
- Breathing difficulties.
- Dehydration;
- hypotonia;
- Hypoglycemia;
- opisthotonus;
- Convulsions;
- Developmental delays;
- Progressive encephalopathy with lethargy.
In the absence of timely treatment, the disease can lead to central respiratory failure, coma and death.
variants
Forms of Maple Syrup Urine Disease
There are four different types of maple syrup urine disease that differ in severity of symptoms and the period of life of the child in which it appears.
Urine syrup with Classic Maple Syrup
The classic form of the maple syrup urine disease is the most widespread and most serious of all. The genetic mutations that cause it are mainly located at the level of the BCKDHA gene. It is characterized by an enzymatic functionality of the branched-chain alpha-ketoacid dehydrogenase equal to or less than 2% of normal activity.
The symptoms triggered by the disease are the same as listed above and occur when the baby starts to take breast milk metabolizing its proteins. In the absence of adequate treatment, the coma occurs within 7-10 days and the implications are tragic.
Intermediate Maple Syrup Urine Disease
The intermediate form of MSUD is a rare form in which the enzymatic activity of the branched-chain alpha-keto acid dehydrogenase complex is slightly higher than the classical form and is about 3-8% of normal activity. The symptomatology is similar to that of the classical MSUD, but may be less severe and start later than the latter.
Intermittent Maple Syrup Urine Disease
The intermittent form of urine syrup of maple syrup is characterized by the late appearance of symptoms, indicatively around the first or second year of age of the child.
Although it is an asymptomatic form after birth, it can cause developmental delays during childhood. Despite this, compared to those mentioned above, the intermittent form is lighter and the enzymatic activity of the branched-chain alpha-keto acid dehydrogenase complex is slightly higher, indicatively, from 8% to 15% of normal activity.
Thiamine-sensitive Maple Syrup Urine Disease
From the clinical point of view, the thiamine-sensitive form of MSUD is similar to the intermediate one and is also a rare form . It is characterized by the fact that the disease improves following the administration of certain concentrations of thiamine (or vitamin B1 if you prefer). In detail, following the treatment with thiamine, there is a greater food tolerance to leucine. Nevertheless, patients must still follow a restrictive diet (see "Care and Treatment" section).
Diagnosis
How to make Maple Syrup Urine Disease Diagnosis?
If the child develops doubtful symptoms, the diagnosis can be made immediately after birth, as part of a newborn screening that normally involves taking a blood sample from the newborn and carrying out various analyzes.
If the child presents the symptoms after the neonatal period, the diagnosis can be made through blood tests, or through urinalysis.
If, on the other hand, there is a known family history of MSUD, then it is possible to perform a prenatal diagnosis by performing specific genetic tests .
Care and Treatment
Treatments and Treatments Against Urine Syrup Maple Syrup
The treatment of the acute phase of the maple syrup urine disease is a real emergency. In such a situation, the primary objective is to decrease the levels of branched amino acids circulating in the body. To do this, it is necessary to enhance protein metabolism by administering glucose, insulin and lipids intravenously. In some cases, hemodialysis may also be necessary.
Once the acute phase of the disease has been controlled, the newborn must be fed with BCAA-free milk (branched amino acids). A BCAA-free diet, or in any case with very low concentrations, must be strictly maintained throughout the life of the patient .
Sometimes orthotopic liver transplantation can be a useful treatment. On the other hand, it is a very delicate surgical procedure which, unfortunately, is not practicable in every patient.
Therefore, leaving aside the possibility of the aforementioned transplant, the emergency treatment of the acute phase and the maintenance of a restrictive and rigorous diet associated with a continuous monitoring of the patient, at the moment, represent the only therapeutic strategy for urine disease. Maple syrup.
Diet for Maple Syrup Urine Disease
The diet for urine syrup of maple syrup is restrictive because it requires to strongly limit - in order to respect the tolerability limit of each individual - all those foods with high protein content, such as meat, eggs and dairy products . At the same time, however, the diet should guarantee the patient the intake of essential nutrients, such as other essential amino acids, mineral salts and vitamins.
A diet so particular and so rigorous, clearly, must be established on a strictly individual basis for each patient by a doctor specialized in this type of metabolism pathologies.
Prognosis
What is Maple Syrup Disease Prognosis?
The prognosis depends on numerous factors including the form of MSUD that affects the patient, the earliness of the diagnosis and subsequent medical intervention.
However, in general, the prognosis can be good for all those patients whose disease is diagnosed early, treated promptly and who follow a strict diet for the duration of their life.
In the event that the maple syrup urine disease is not diagnosed early, the consequences could prove tragic.
