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Pediatric Diseases: Congenital Metabolic Disorder

What is Congenital Metabolic Disorder?

The term of “Congenital” in Congenital Metabolic Disorder means, in broad sense, disease status already exists before birth, and in narrower sense, the change which causes a disease has been contained in Gene, i.e. the disease is a genetic origin.

“Metabolic Disorder” means the disease status where metabolism of body construction integrant (carbohydrate, protein, fat), and energy production, does not function.

“Metabolism” means, for example, to convert the matter like glucose sugar to other body useful matter, or to produce energy in the process of conversion. “Enzyme” is mainly assumes the conversion of the matter (metabolize), and saying simply in classical terms, Congenital Metabolic Disorder is the gene disorder which produce enzyme. However, recent research clarifies further complexed metabolism mechanism, so that gene disorder other than enzyme becomes known. Organization exclusively research in this field of disease is “Japanese Society for Inherited Metabolic Disorder (

The classification and cause of congenital metabolic disorder.

Congenital Metabolic Disorder covers wide variety of diseases, for example, corresponding to metabolized matter, they are classified with, amino-acid metabolism abnormality, ammonia metabolism disorder, glucose metabolism disorder, organic acid metabolism disorder, fatty acid metabolism disorder, abnormality of lipid metabolism, metal metabolism disorder and nucleic acid disorder. On the other hand, there might be a case where they are classified with symptom appeared organ (ex. Metabolic neuromuscular disorder) or subcellular organelle (ex. Mitochondrial disease).

In the field of medical research, under these large classification, disease name which uses disordered enzyme name, or gene name which is the layout drawing for these enzyme, many diseases are grouped. However, understanding of the disease that is associated with gene disorder had not been done in the past, and disease names used at daily medical care are not necessarily associated with gene disorder only, because disease name associated with symptom or treatment are more easy to understand and useful.

For example, disease name “phenyl ketonuria”, which is named in the past century, , is used even nowadays, because phenyl ketone is increased in urine, but this disease should rather be called as “phenylalanine hydroxylase deficiency” or “phenylalanine hydroxylase genetic abnormality”. Furthermore, since this disease makes phenylalanine in blood increased, it may be called as “high phenylalanine blood disease”. Decreasing phenylalanine density in blood by diet therapy is useful treatment, the name using accumulated amino acid is easy to understand and convenient. Also, similar symptom may occur with the disorder of coenzyme which helps the function of phenyl alanine hydroxylase enzyme, so that it is mixed-up with phenyl ketonuria”, but they are different in the treatment so that disease name of “biopterin metabolic abnormality” is used separately.

Another important point is, even in case some transformation occurs in phenylalanine hydroxylase gene, there are few levels exists in that gene transformation, and they are named in accordance with the level of severity. The most severe case is named as “phenyl ketonuria”, mild to medium case is “hyperphenylalaninemia”, and for the case where increase of blood phenylalanine is mild so that no symptom appears through life without any treatment, is named as “asymptomatic” or “the mildest form” hyperphenylalaninemia. Transformation of these “asymptomatic” gene is called as “variant” so that it is differentiated from pathological transformation “genetic mutation”. Although it is diagnosed as phenylalanine hydroxylase deficiency based on the transformation of relative enzyme, it is necessary to take note that the severity of the symptom varies.

As mentioned above, classification of congenital metabolic disorder covers a lot of ground and there exists a lot of disease name, but appearance provability of each disease is extremely rare like one out of tens to hundreds of thousands so that it is called as “scarcity disease”.

How to appear and how to recognize Congenital Metabolic Disorder.

Metabolism is performed at several organs in the body so that the appearance of disorder has a huge variety. You can check each disease symptoms from the Association homepage. Here we explain the appearance characteristics of congenital metabolic disorder symptoms.

As aforementioned, appearance of the disease is different from each disease’s severity, although it is named as enzyme abnormality (or deficiency). Severer disease symptom appears earlier. In case of the most severe type disease, significant symptom already exists on fetus before birth. Also, there is a case where severe symptom appears immediately after birth (from neonatal infant). For the disease type not so severe, severity is expressed by symptom appearance timing. For example, neonatal type means severe type, infant type means milder than neonatal type but relatively severe symptom, adult type means relatively mild case.

While for severe congenital metabolic disorder patients, treatment is difficult, and they are in transitory life, on the other hand, for relatively mild case patients, symptom does not appear after birth but soon brain disorder is developed. They are the characteristics of congenital metabolic disorder so that the purpose of the treatment is to prevent this brain disorder. However, once brain disorder occurs, for almost all cases, patients does not make recovery although applying enough treatment, so that it is necessary to diagnose immediately after birth and to start treatment at earlier stage as possible. To find earlier of the part of congenital metabolic disorder which has an approach to treatment, “newborn mass screening” is conducting in many countries throughout the world including Japan.

Examination and diagnosis should be made at the specialized Medical Organization.

Variety of special medical equipment are necessary to diagnose congenital metabolic disorder, but most of them are not subject to the medical insurance coverage, so that they are currently operated at University Research Facility or special examination organization. Which examination is made at which organization can be searched at the Japanese Society of Inherited Metabolic Diseases homepage. Normally, it is difficult for general hospital doctor to diagnose this scarcity disease patient, so that patient is tested and diagnosed at University Hospital or other specialized hospital which is specialized for congenital metabolic disorder.

Explaining briefly about examination and diagnosis, which metabolic disorder is presumed from symptom and result of general clinical examination, then analyze thoroughly abnormal metabolite contained in blood or urine to squeeze in specific disease among them. Especially, since urine contains lot of metabolite related with the disease, test is conducted with using special test equipment like mass analyzer. In already explained newborn mass screening, it cyclopaedically investigate the metabolite in blood.

When specific disease (abnormal disease) is presumed from these cyclopaedically examination result, “enzyme” function (oxygen activation) related with said abnormal disease is measured. In case it has found there is a problem in enzyme, gene, which is the layout drawing for these enzyme, is then checked. These are checked using blood drawing.

Effective treatment is “diet therapy”.

Congenital Metabolic Disorder has a problem in gene itself, and it is difficult to completely cure for this genetic problem. But, by the improvement of recent medical research, many which is not versatile but useful and effective, treatment method is getting developed.

Also, there exists an abnormal disease which the onset of the disease can be controlled by means of applying early treatment from neonatal period. So that to find the said disease, newborn mass screening is conducted and/or planned.

Not a basic remedy but effective treatment method is represented by “Diet Therapy”. Principle is not to take materials which is difficult for metabolizing due to disease reason. For already mentioned phenyl ketonuria (hyperphenylalaninemia), when phenyl alanine contained protein intake is reduced, density of phenyl alanine in the body becomes close to healthy person thus turns into no symptom appeared.

Other than Diet Therapy, there are; the treatment taking medicine supporting enzyme function, or treatment injecting enzyme itself. In case disease is developed at specific organ (tissue), transplant surgery may be conducted in receiving donor’s liver or bone marrow. Recently, treatment using gene or gene transforming material has started to use.

These treatment does not mean that when it has once tried these diseases have completely cured, so that it is necessary to continue treated. Because, rare disease, like congenital metabolic disorder which can be diagnosed correctly, has just recently found out. And in fact, how does symptom appear with how to follow process, are just recently known. Almost all aforementioned treatment has just start recently, so that its effect is not yet confirmed in full. So that it is important to continue periodical examination and test at the hospital which is specialized in diagnosis and treatment for congenital metabolic disorder and verify whether the treatment is going well as planned.

Details of individual treatment for congenital metabolic disorder can be checked at Japanese Society of Inherited Metabolic Disease homepage.