Metabolic Diseases in the Baby
July 11th, 2010 | 
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In 1902 Sir Archibald Garrod noted that some of their patients had conditions that persisted throughout life and are produced by a defect in the activity of an enzyme or a transport process within the cell that results in the alteration of a metabolic pathway determined and a block on the biochemical reactions of this course and patients described what came to be called “inborn errors of metabolism”: albinism, cystinuria (disorder characterized by stones in the kidneys, ureter and bladder caused by excessive secretion certain amino acids (building blocks of proteins) due to a genetic abnormality) and alkaptonuria (rare metabolic disorder characterized by urine that turns dark on exposure to air and the development of arthritis in adulthood).
Most of these defects are inherited in an autosomal recessive or X-linked, so there is not always a history of disease in parents, only a few are inherited in dominant form.
Early detection of such conditions allows appropriate treatment early and this improves the prognosis of these patients to stop the progression of the disease and its complications and sequelae.
How are inborn errors of metabolism (IEM)?
Currently about 500 known inborn errors of metabolism (IEM) which are classified according to the metabolic pathway is altered, the role of the enzyme concerned, of substances related to it or involved in cell body the metabolic pathway affected.
There are three main groups:
1. By the accumulation of large or complex molecules.
2. For toxicity caused by small molecules
3. By defects in the production or use of energy
GROUP I: at-large complex molecules
These include diseases that affect the production or degradation of complex molecules such as would all the components of cell membranes or tissues. The symptoms will be permanent, progressive, independent of other diseases and are NOT related to food. This group of diseases lysosomes or peroxisomes which are basic components of the cell.
GROUP II: small molecules for toxicity
EIM includes leading to acute or progressive intoxication due to the accumulation of toxic compounds. To this group belong
* Disorders in the metabolism of some amino acids phenylketonuria, urine disease maple syrup smell
* Disturbances in carbohydrate metabolism: galactosemia, hereditary fructose intolerance.
* Disruption of the urea cycle.
The diseases in this group have clinical similarities, including symptom-free intervals alternate with signs of intoxication may be acute. Imbalances are often accompanied by systemic or widespread:
* Acidosis (a condition characterized by excess acid in body fluids).
* Ketosis (a state of acidosis is characterized by the presence of high concentrations of acetone in blood and urine.
* Hyperammonemia (metabolic disorder characterized by high levels of ammonia in the blood)
* Hypoglycemia (low blood glucose)
The diagnosis is usually simple and is based on the study of blood and urine amino and organic acids
GROUP III: defects in production or use of energy
In these cases the body does not include the energy needed for normal operation, since an overall multi-organ failure, being the organs most commonly affected:
* Liver
* Myocardial (heart muscle)
* Striated muscle
* Central nervous system (brain)
Are common diseases?
IEM are rare genetic conditions individually but collectively numerous. The number of metabolic diseases is steadily increasing to the extent that we have new concepts and techniques for the identification of biochemical phenotypes (phenotype is any detectable characteristic of an organism (eg, structural, biochemical.
on physiological and behavioral) determined by an interaction between genetic information and its environment).
The incidence varies between different races, for example, CF has an incidence of 1 in 1600 newborns of European descent, sickle cell anemia occurs in 1 in every 600 live births of African parents and Tay Sachs disease is 1 in 3,500 live births Ashkenazi Jews.
What are the main symptoms of inborn errors of metabolism?
The EIM can affect any organ or system and sometimes several of them simultaneously. The manifestations depend on the affected pathway and the intensity of default. They tend to progress rapidly and impair the patient’s condition within hours or it may manifest as episodic decompensation and lapses with asymptomatic (without signs or symptoms) or have an evolution that will take decades to manifest clinically. The age at which symptoms begin to appear, depends on the metabolic error.
There is great diversity of signs and symptoms that guide the physician to the diagnosis of EIM and we will be separated into five basic groups according to age of presentation and form of presentation of them:
1. Acute symptoms in the neonatal period
2. Late-onset symptoms
3. General symptoms and progressive chronic
4. Characteristic symptoms and permanent
5. Congenital malformations
1) Acute symptoms in the neonatal period
This is usually a term infant, apparently healthy in their first hours of life, which after a few hours or days of power begins to deteriorate for no apparent reason and does not respond to symptomatic treatment, but all these symptoms can begin in pregnancy or presented in the immediate neonatal period (forms of energy deficit and inborn errors of metabolism of complex molecules).
There are no specific symptoms of a metabolic disorder in this period of life. The clinical manifestations of the newborn are limited and nonspecific and often attributed to other common processes such as sepsis (generalized infection) or respiratory distress syndrome (also often accompany metabolic diseases). However, there are some common forms of presentation of the EIA in this age:
* Neurological or neuromuscular symptoms: is the most common in the newborn. Disorders of sucking and swallowing, vomiting, hypotonia (low muscle tone), respiratory distress, lethargy or fatigue, convulsions, coma, and CNS malformations.
* Symptoms Liver: hepatic failure (liver failure) in neonatal fulminant is usually due to an inborn error of intermediary metabolism (which is made or occurs in a middle stage).
* Symptoms Cardiac rhythm disorders mainly or progressive cardiomyopathy.
* Other signs: progressive failure of all systems (multi-system failure), dysmorphic syndromes, blood disorders, kidney, skin, etc., Can be just an expression of neonatal EIM.
There is a bit more specific elements, like the smell of the newborn, which can be very characteristic. The most characteristic odor of burnt sugar is maple syrup, typical of the second most common metabolic disease, the disease-smelling urine maple syrup. The smell of sweaty feet seen in isovaleric acidemia (disorder where people can not fully break down proteins) and glutaric aciduria type 2 (is an inborn error of metabolism of the essential amino acids lysine and tryptophan), the smell of cat urine in multiple carboxylase deficiency (defects of the intermediary metabolism of carbohydrates associated with lactic acidosis.; tyrosinemia (caused by the deficiency of the enzyme terminal degradation pathway of tyrosine) is characterized by the smell of cooked cauliflower, and phenylketonuria, smells of damp and mouse.
Given the clinical suspicion of an EIM physicians should initiate a study of additional tests to confirm that suspicion and guide the baby’s diagnosis.
The interval between birth and the onset of symptoms can vary from hours to weeks depending on the degree of metabolic block, environmental conditions and feeding the baby is receiving. In general, all studies of routine that makes them normal (chest radiograph, cerebrospinal fluid analysis, bacterial cultures and cerebral ultrasound).
THIS UNEXPECTED AND MYSTERIOUS DETERIORATION AFTER A NORMAL PERIOD IS THE MOST IMPORTANT KEY TO SUSPECT THE PRESENCE OF AN EIM.
How is an energy deficit type box?
In the EIM energy production, both production and energy use are affected. T he symptoms come on quickly after childbirth or after a few hours of birth and the property is a serious commitment to life and if nothing is done giving energy, death ensues.
The clinical presentation is diverse and their severity but there is no period without symptoms.
The most common symptoms are:
* Loss of strength or muscle tone widespread
* Growth of abnormal heart
Rapidly progressive neurological deterioration *
* Congenital malformations
They are also frequent low blood sugar and lactic acid elevation in plasma.
2) Late submission
In almost one third of babies with IEM, the appearance of symptoms is delayed. The interval without symptoms may be a year or more or appear in adolescence and adulthood. The disease can occur when there is a crisis, either by presenting a minor viral infection, fever, severe constipation or excessive intake of protein.
The clinical data of late onset may be acute and recurrent these are:
* Ataxia or loss of balance
* Vomit
* Metabolic acidosis
3) chronic and progressive clinical manifestations
Usually produce digestive and neurological manifestations. Digestive diseases such as anorexia or loss of appetite, vomiting, chronic diarrhea and growth arrest are frequently attributed to other conditions and are misdiagnosed as intolerance to milk protein, celiac disease, gastrointestinal infections and pyloric stenosis among others. There are a number of neurological symptoms at the same time also often confused with other illnesses or are misdiagnosed, which include mental retardation, dystonia or torsion of a limb, stiffness, Parkinson’s, dementia, epilepsy, or intellectual impairment
4) Clinical features and permanent:
There are a number of signs and symptoms that may alert the physician to make the diagnosis of EIA. For example, the dislocation of the lens of the eye and thromboembolic events that occur in homocystinuria (amino acid metabolism disorder of methionine), dark urine that occurs in alkaptonuria (disorder of the metabolism of tyrosine) and cherry-red spot at the bottom eye is typical of gangliosidosis (group of inherited diseases caused by an accumulation of gangliosides, a type of chemical found in nerve tissue, especially in neurons) and Tay Sachs disease common in Jews.
5) Congenital malformations associated with inborn errors of metabolism
The vast majority of EIM not occur with birth defects, which explains that the organ damage is later because in the perinatal period often maternal metabolism fetal overcome their deficiencies. Many babies with accumulation of complex molecules show changes at birth as congenital cataracts in galactosemia. The dysmorphic facial features or rare conditions are shown in energy deficit and are frequently: the middle of the face as well as small and malformed kidney cysts, small head, fingers, more so. as in the Smith Lemli Opitz Syndrome.
What is the importance of diagnosis for EIM?
In all cases, because they are genetic diseases, accurate diagnosis is essential for proper genetic counseling to the family. For parents of the patient is up to 25% risk of recurrence. EIM For those with specific treatment, accurate diagnosis is essential for the couple to offer prenatal diagnosis in subsequent pregnancies.
Do they treat these diseases?
For some forms of acute onset (newborn and intermittent acute forms more later), emergency treatment is aimed at reducing the production of toxic metabolites proximal to freezing point and at the same time stimulating anabolism (one of the two parts of metabolism responsible for the synthesis or formation of more complex molecules from simpler ones) with a high energy intake.
On the other hand, depending on the severity of symptoms, can be used exogenous detoxification measures such as exchange transfusion, peritoneal dialysis, hemodialysis, and in some cases, increase the elimination of toxic product. Liver transplantation, the contribution of diet and enzyme permanent restraining are other treatments that may apply. Finally, there is a group of IEM that does not have specific treatment.