Diseases

Glycerol Kinase Deficiency – Causes, Symptoms & Treatment

Glycerol kinase deficiency

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?

A glycerol kinase deficiency is a rare metabolic disease in four different forms, which can be treated genetically and belongs to the category of hereditary diseases. The metabolism is attacked because in the liver the glycerol is not converted into glycerol-3-phosphate.

Rather, oxidation or phosphorylation occurs, resulting in glycerol alehyd-3-phosphate or glycerol-2-phosphate. The signs range from freedom from symptoms to physical complaints and laboratory indications. Diagnosis can be made pretanally and postnatally by means of differential and molecular diagnostics.

Mental retardation as well as muscular and vertebral disorders can occur. Therapeutically, substitution with glucocorticoids and a low-fat diet is announced. Preventive measures are not yet known.

Causes

In the first place, an X-linked recessive genetic defect should be mentioned. In relation to chromosome Xp21.3. Lacation Xp21.2 is based on mutations of the disease in the GK gene. The clinical criteria relate to growth disorders, mental retardation, osteoporosis with a tendency to fracture.

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

This uses glycerol kinase 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. It produces glyceraldehyde-3-phosphate or glyceric acid-2-phosphate. As a result, not only the metabolism is attacked. 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 clinical criteria with muscular dystrophy (hereditary muscle wasting with increasing muscle weakness) and congenital adrenal hypoplasia (genetic underdevelopment of the kidney with insufficient cell formation). Another cause of glycerol kinase deficiency lies in apolipoprotein C2 as a component of lipoproteins that help transport lipids through the blood.

Symptoms, complaints & signs

The symptoms are very versatile but can be reproduced very well by those affected, so that an anamnesis can be carried out very well and extensively on the basis of the patient’s presentation. Starting with a freedom from symptoms to vomiting, recurrent sweats also appear, especially during exertion and before eating.

In the laboratory, not only hypoglycemia (too low blood sugar levels) can be detected. Rather, the laboratory parameters in the blood and urine (hyperglyceremia and hyperglyceruria) are increased. An enzyme deficiency and pseudohypertriglyceridemia (feigned triglyceride elevation in the blood) can also be detected.

Ketoacidosis (dangerous metabolic derailment due to insulin deficiency) and 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, among other things on the basis of 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. Free glycerol with elevated levels is detectable in urine and blood serum. If there is a medical indication, the laboratory examination is carried out by means of a referral form.

Differential diagnosis includes the very rare Snyder-Robinson syndrome. This is a congenital disease that can mainly present itself with mental retardation, muscle atrophy, osteoporosis or kyphoscoliosis (unphysiological, dorsally directed spinal curvature) but also an asymmetry of the face and gait uncertainty.

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

Complications

The glycerol kinase deficiency leads to very different symptoms. In most cases, however, vomiting occurs, which is accompanied by heavy sweating in patients. The quality of life is significantly limited by the symptoms, which in most cases occur immediately after eating food.

It also comes to motor complaints, so that ordinary activities in everyday life can no longer be carried out. Most sufferers also suffer from increased retardation and are dependent on the help of other people in their everyday lives to master it. Not infrequently, there are also movement disorders and gait uncertainty, 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 takes place only in the form of a suitable diet. This diet must be relatively low in fat so that the deficiency can be eliminated. With early diagnosis, many symptoms can be reduced and consequential damage avoided.

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

When to go to the doctor?

As a rule, glycerol kinase deficiency should always be examined by a doctor. In this disease, self-healing does not occur. The symptoms usually increase and have a very negative effect on the quality of life of the person concerned. A doctor should be consulted if vomiting occurs very frequently and, above all, for no reason. However, severe sweating can also indicate glycerol kinase deficiency and should be investigated. Especially after ingestion of food, these can occur.

In many cases, glycerol kinase deficiency also leads to mental and motor retardation. This can be determined mainly by the parents or by the relatives and should also be examined by a doctor. First and foremost, a visit to a or a paediatrician is 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 lack of lipoprotein lipase 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. As a result, patients experience a significant alleviation of existing complaints and can enjoy their lifestyle in many other areas without complaints.

In severe cases, the deficiency also leads to regular administration of medicines. This ensures the survival of the patient. The metabolism is stimulated by the drugs and ultimately monitored in order not to trigger complications or sequelae. Refusal of medical care can lead to serious disturbances and complaints. 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

To date, medical research has not succeeded in developing effective 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 affected person 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.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.