Glycerol Kinase Deficiency Explained

Glycerol Kinase Deficiency Explained

Glycerol kinase deficiency, also known by the synonyms GK deficiency, glycerol kinase deficiency, hyperglyceremia or ATP-glycerol-3-phosphotransferase deficiency, is a metabolic disease that can be treated in the Department of Human Genetics. A distinction is made between isolated, infantile, juvenile and adult glycerol kinase deficiency.

What is Glycerol Kinase Deficiency?

According to digopaul.com, a glycerol kinase deficiency is a rare metabolic disease in four different forms that can be treated with human genetics and belongs to the category of hereditary diseases. The metabolism is attacked because the glycerol is not converted into glycerol-3-phosphate in the liver.

Instead, oxidation or phosphorylation occurs, resulting in the formation of glycerol aldehyde-3-phosphate or glycerol-2-phosphate. The signs range from the absence of symptoms to physical complaints and laboratory indications. The diagnosis can be made prenatally and postnatally using differential diagnostics and molecular diagnostics.

A mental disability as well as muscle and vertebral diseases can be adjusted. Therapeutically, substitution with glucocorticoids and a low-fat diet are recommended. Preventive measures are not yet known.

Causes

First and foremost is an X-chromosomal recessive inherited gene defect. Namely related to the chromosome Xp21.3. At the Xp21.2 lacation, mutations in the GK gene underlie the disease. The clinical criteria relate to growth disorders, intellectual disability, osteoporosis with an existing tendency to fracture.

During fat digestion, glycerol is released in the intestine, absorbed by the tissues and transported to the liver. In the liver, glycerol kinase converts glycerol into glycerol-3-phosphate. For this, the enzyme not only needs the substrate but also adenosine triphosphate, or ATP for short. When this phosphate is split, energy is released.

Glycerol kinase uses this to catalyze the biochemical reaction with glycerol-3-phosphate. If this conversion does not take place, oxidation or phosphorylation (reversible attachment of a phosphate group to an organic molecule in biochemistry) can occur. Glyceraldehyde-3-phosphate or glyceric acid-2-phosphate is formed. This not only affects the metabolism. Rather, there are dangerous interventions in the metabolism with regard to the processing of fats and carbohydrates.

In rarer cases, there is a combination of the clinical criteria with muscular dystrophy (hereditary muscle wasting with increasing muscle weakness ) and congenital adrenal hypoplasia (genetic underdevelopment of the kidneys with insufficient cell formation). Another cause of glycerol kinase deficiency lies in apolipoprotein C2, a component of the lipoproteins that help transport lipids through the blood.

Symptoms, Ailments & Signs

The symptoms are very varied but can be reproduced very well by those affected, so that an anamnesis can be taken very well and comprehensively on the basis of the patient’s description. Starting with the absence of symptoms and continuing with vomiting, there are also recurrent outbreaks of sweating, especially during exertion and before eating.

Not only hypoglycemia (too low blood sugar level) can be detected in the laboratory. Rather, the laboratory parameters in the blood and urine (hyperglycerinemia and hyperglycerinuria) are increased. An enzyme deficiency and pseudohypertriglyceridemia (faked increase in triglycerides in the blood) can also be detected.

A ketoacidosis (dangerous metabolic derailment due to lack of insulin) and a mental motor retardation, measured against the average of the relevant age group, can expand the possible symptoms.

Diagnosis

The diagnosis is made postnatally as part of a molecular genetic examination using, among other things, a DNA sequence analysis of the GK gene. This requires three to five ml of EDTA blood. The result is available after two to three weeks. High levels of free glycerol can be detected in urine and blood serum. If there is a medical indication, the laboratory test is carried out using a referral slip.

Differential diagnosis includes the very rare Snyder-Robinson syndrome. This is a congenital disease that can present itself mainly with a mental disability, muscular atrophy, osteoporosis or kyphoscoliosis (unphysiological, dorsal curvature of the spine) but also asymmetry of the face and unsteady gait.

A diagnosis is also possible in the prenatal stage. The entire laboratory diagnostics can be based on biochemical and molecular diagnostics as well as on heterozygous screening using NGS. The “diagnosis of intellectual disability” as a postnatal diagnosis applies to the search for mutations, mutation screening and sequencing.

Complications

The glycerol kinase deficiency causes very different symptoms. In most cases, however, vomiting occurs, which is accompanied by severe sweating in patients. The quality of life is significantly reduced by the symptoms, which in most cases occur directly after eating food.

There are also motor problems, so that normal activities in everyday life can no longer be carried out. Most of those affected also suffer from increased retardation and are dependent on the help of other people in their everyday life in order to master this. It is not uncommon for there to be movement disorders and an unsteady gait, so that the patients suffer from an increased risk of falling and accidents.

It is not possible to treat glycerol kinase deficiency directly, so treatment only takes the form of an appropriate diet. This diet must be relatively low in fat for the deficiency to be eliminated. With an early diagnosis, many symptoms can be limited and consequential damage avoided.

Although the life expectancy is not reduced by the disease, the everyday life of the patients is considerably restricted. The parents and relatives of the patients also suffer greatly from the glycerol kinase deficiency from psychological complaints and possibly from depression.

When should you go to the doctor?

As a rule, a glycerol kinase deficiency should always be examined by a doctor. This disease does not heal itself. The symptoms usually increase and have a very negative effect on the quality of life of those affected. A doctor should be consulted if vomiting occurs very frequently and, above all, without reason. However, heavy sweating can also indicate a glycerol kinase deficiency and should be examined. These can occur especially after eating.

In many cases, the glycerol kinase deficiency also leads to mental and motor retardation. This can be determined primarily by the parents or by relatives and should also be examined by a doctor. A visit to a general practitioner or a pediatrician is primarily suitable for this. The treatment itself depends on the exact symptoms and also on the cause of the deficiency. Early diagnosis and treatment has a positive effect on the course of the disease.

Treatment & Therapy

Treatment consists of a low-fat diet. If there is also adrenal hypoplasia, substitution with glucocorticoids may not only be important, but even vital. For a suitable therapy to limit the possible secondary diseases, it is important to recognize the disease as early as possible and to treat it accordingly.

In this regard, prenatal diagnostics is a milestone in differential diagnostic and molecular diagnostic medicine. Glycerine occurs in all fats and fatty acid esters (triglycerides = triple esters of glycerine). The level of concentration of these triglycerides in the blood is the indicator of human health.

The following values ​​can be used as a basis for a planned therapy: If the triglyceride value is over 150 milligrams per dl, it is classified as too high and can indicate a lipid metabolism disorder (hypertriglyceridemia). One reason for this can be a genetic predisposition on the one hand and a lipoprotein lipase deficiency on the other.

Outlook & Forecast

If medical support is sought, the prognosis for glycerol kinase deficiency is usually favorable. Patients with the hereditary disease are exposed to lifelong therapy because the genetic defect cannot be remedied for legal and scientific reasons.

Depending on the severity of the disease, it is often sufficient if a special low-fat diet is developed and adhered to. The patients experience a significant alleviation of the existing symptoms and can enjoy their lifestyle free of symptoms in many other areas.

In severe cases, the deficiency means that medicines are also given regularly. This ensures the survival of the patient. The metabolism is stimulated by the medication and ultimately monitored in order not to trigger any complications or consequences. Refusal of medical care can lead to serious disturbances and complaints. The average life expectancy is also falling.

If the patients suffer from mental retardation due to the glycerol kinase deficiency, the prognosis is unfavorable. Despite support programs and timely medical care, this cannot be compensated for or remedied in the necessary form. The patient is lifelong dependent on help and support in coping with everyday life. Nevertheless, an improvement in the quality of life can also be achieved here by adhering to a diet and the administration of medication.

Prevention

Medical research has not yet succeeded in developing targeted measures within the framework of prophylaxis. Thus, the best way to target treatment early on is to detect glycerol kinase deficiency as early as possible.

Aftercare

In the case of a glycerol kinase deficiency, the patient usually has no special follow-up measures available. The person affected is primarily dependent on medical treatment, although complete healing is usually not possible. The complaints can only be treated purely symptomatically and not causally.

If the person concerned wishes to have children, genetic counseling and testing can also be carried out to prevent the recurrence of the glycerol kinase deficiency in the offspring. This deficiency is usually treated with a special diet. The person affected must pay attention to a low-fat diet in order to counteract the deficiency.

In cases of doubt, the treating doctor can also draw up a plan for the person concerned, which can support the diet. Since the glycerol kinase deficiency can also lead to other diseases and complications, regular examinations of the entire body are very useful. In some cases, the deficiency also reduces the life expectancy of those affected.

In general, a healthy lifestyle with a balanced diet has a positive effect on the course of the disease. Contact with other patients who suffer from glycerol kinase deficiency can also be useful, as it is not uncommon for information to be exchanged.

You can do that yourself

It is not possible to treat glycerol kinase deficiency with self-help methods. For this reason, those affected are always dependent on medical treatment. This usually involves the use of substitutes to compensate for the deficiency. Often, these drugs have to be taken throughout life in order to permanently limit the symptoms. The person concerned should therefore ensure that they take these medications regularly.

Furthermore, an early diagnosis of the glycerol kinase deficiency is very important, as this can prevent further diseases and consequential damage. Therefore, a doctor should be consulted at the first sign of a glycerol kinase deficiency.

If the glycerol kinase deficiency is a genetic disease, those affected and their parents should undergo genetic counseling, as this can prevent the disease from occurring in other children.

Furthermore, contact with other people affected by the disease often has a positive effect on the disease, since this can lead to an exchange of information. These can make everyday life easier and improve the quality of life of those affected. Children should be fully informed about the disease and its possible consequences.

Glycerol Kinase Deficiency