Wolmans Disease: Causes, Symptoms & Treatment

Wolman disease is a lysosomal storage disease inherited in an autosomal recessive manner. In the disease, there is a loss of activity of the so-called lysosomal acid lipase. Wolman disease is relatively rare.

What is Wolman disease?

Wolman disease is a genetic disorder in which there is a defect in the lysosomal acid lipase enzyme. The enzyme is necessary to metabolize specific lipids in the body. Consequently, metabolization is impaired. Wolman’s disease is always inherited in an autosomal recessive manner. The gene encoded for acid lipase is located on chromosome number 10. Lipid storage disease (medical name xanthomatosis) in Wolman disease is characterized by calcification of the adrenal glands, which in most cases begins in the first days of life.

Causes

The main cause of Wolman disease is found exclusively in an inheritance of a genetic defect. The disease is due to a complete loss of lipase function, caused by mutations on the so-called LIPA gene. This enzyme is responsible for the cleavage of lysosomes into cholesterol esters and triacylglycerides, which are absorbed into the corresponding cell in an endocytotic manner in the form of the substance LDL, a special lipoprotein. Under normal circumstances, cholesterol is formed in free form during this process, which is transported to the so-called cytosol and is responsible for the regulation of cholesterol synthesis in the endoplasmic reticulum. In the presence of Wolman’s disease, cholesterol esters accumulate in the lumens of the lysosomes. At the same time, the normal process of cholesterol synthesis is disturbed, so that more and more lipoprotein LDL is absorbed. Increasing accumulation of the substances cholesterol esters and triacylglycerides takes place, resulting in cell death in the long term.

Symptoms, complaints, and signs

A number of symptoms of various types may occur as part of Wolman disease. These symptoms are primarily caused by the excessive accumulation of lipids in the body. The symptomatology of Wolman’s disease is characterized by that of cholesterol ester storage disease, although some residual lipase activity is still present. The symptoms of Wolman’s disease appear early and in many cases occur immediately after the birth of the affected patient. In Wolman’s disease, for example, gastrointestinal complaints in the form of flatulence, swelling in the abdominal area and a bloated abdomen, vomiting and, in addition, a pronounced enlargement of the liver and spleen (medical term hepatosplenomegaly) can occur as possible symptoms. As a consequence of necrosis, enlargement as well as calcification of the adrenal glands may occur. Symptoms such as hypercholesterolemia as well as hyperlipidemia may also occur. In addition, life-threatening complications may develop, in many cases in early childhood.

Diagnosis and disease progression

At the first symptoms of Wolman’s disease, detailed specialist examinations are ordered immediately, within the framework of which it becomes possible to make an accurate diagnosis. In most cases, a laboratory-chemical blood analysis is performed, which can reveal changes in lipid patterns. In most cases, foam cells appear. Liver biopsy is another possible tool for diagnosing Wolman’s disease. Here, unusually strong accumulations of lysosomes can be detected in the so-called hepatocytes, which can provide information about the disease. Wolman’s disease can be distinguished from other lysosomal storage diseases by means of enzymatic activity tests and genetic analyses, which can identify mutations in the respective genes. Diagnostic methods such as X-ray and sonography can be used to determine the presence of Wolman’s disease. Wolman disease usually leads to death within the first year of life.

Complications

The symptoms of Wolman disease can vary widely. For this reason, early treatment is also not possible in many cases because the symptoms and complaints are not characteristic.Patients suffer from flatulence and constipation. It is not uncommon for patients to also suffer from a loss of appetite and psychological complaints due to the permanent problems in the stomach area. It is not uncommon for patients to suffer from a bloated abdomen and swelling. Furthermore, nausea and vomiting may also occur. The symptoms of Wolman’s disease can significantly restrict the development of children. Not sailing children are thereby bullied or teased and can also develop psychological complaints as a result. A causal treatment or therapy of this disease is not possible. The complaints themselves can be treated and limited symptomatically, and there are usually no particular complications. However, patients are dependent on lifelong therapy, since a completely positive course of the disease does not usually occur. However, Wolman disease does not reduce the life expectancy of the affected individual.

When should you see a doctor?

Wolman disease usually manifests in the first few weeks of life. If it is not detected immediately after birth, a doctor should be consulted at the latest when the known symptoms appear. For example, recurrent abdominal pain, diarrhea or vomiting in the child must be clarified by a doctor so that complications do not arise and any Wolman’s disease is detected at an early stage. If growth retardation or chronic fever develops, inpatient treatment may be necessary. In any case, the actual therapy must be closely monitored. Treatment is carried out by the family doctor and various specialists in infectious diseases and internal diseases. If the course of treatment is positive, the parents of the affected child should also involve a physiotherapist in the treatment. Since Wolman’s disease is fatal in most cases, a therapist should be involved to accompany the medical treatment. Palliative medical measures should also be initiated together with the responsible physician to ensure comprehensive care for the affected person in the last stage of life.

Treatment and therapy

To date, no specific treatment methods exist for the therapy of Wolman’s disease. As a rule, therapy is merely symptomatic. For example, the affected patient is administered so-called HMG-CoA reductase inhibitors or must take inhibitors of apolipoprotein B synthesis or cholesterol synthesis. In recent years, successful enzyme replacement therapies have also been developed as part of various clinical programs, which can be used for various lysosomal storage diseases and also in the presence of Wolman’s disease. The corresponding enzyme is supplied externally at regular intervals, which can lead to a reduction or even reversal of the symptoms. In addition, the removal of any polyps can be considered as a surgical therapy for Wolman’s disease.

Outlook and prognosis

Wolman’s disease is very much a rare disorder that usually leads to the death of the child within the first three to six months of life. Infants with the disease die within the first year of life. The prognosis is accordingly poor. Since 2015, a specific enzyme replacement therapy has been offered in Germany, which can prolong life expectancy. The infusion takes place every two weeks and thus represents a permanent burden for those affected, as corresponding specialist clinics offering the therapy are only available in small numbers in Germany. However, enzyme replacement therapy can significantly improve the quality of life. In combination with other treatment measures such as medicinal pain management and symptomatic therapy of liver complaints, children with the disease can lead a relatively symptom-free life in individual cases. Long-term studies on the course of Wolman’s disease do not yet exist due to the rarity of the disease. The final prognosis is made by the responsible specialist. The general practitioner or a specialist in genetic diseases is responsible, who makes the prognosis with regard to the individual symptoms and constitution of the patient.

Prevention

Since Wolman’s disease is an inherited disease, there are no options for preventive measures.Should corresponding symptoms and signs characteristic of the disease appear, detailed specialist examinations of the affected patient must be carried out immediately. In this way, the possible presence of Wolman’s disease can be quickly diagnosed and treated accordingly. This can alleviate any symptoms of the disease that do occur and reduce the likelihood of potentially dangerous complications occurring. In general, however, Wolman disease is an exceedingly rare condition, with an estimated incidence of approximately 1 in 700,000.

Follow-up

In most cases of Wolman’s disease, very few and usually very limited follow-up care measures are available to the affected individual. It is a congenital disease that also cannot be completely cured. Therefore, the person affected by this disease should consult a doctor at an early stage in order to prevent the occurrence of further complications and complaints. Self-cure is not possible. In case of Wolman’s disease, a medical examination should be performed in order to prevent the recurrence of the disease. Patients with Wolman’s disease are usually dependent on taking various medications that can permanently alleviate and limit the symptoms. The correct dosage and regular intake should always be ensured in order to alleviate the symptoms. Regular checks and examinations by a doctor are also very important in order to detect and treat further damage at an early stage. Due to the disease, many patients are also dependent on the support of their own family, whereby psychological support is not infrequently necessary. As a rule, Wolman disease does not reduce the life expectancy of the affected person.

What you can do yourself

Therapy for the symptoms associated with Wolman disease is either symptomatic or enzyme replacement therapy. However, to date, the proven efficacy of these treatments is controversial. In the case of the disease, which already shows itself in the first days of life, self-help possibilities by the parents apart from medical applications are hardly possible. As a supportive measure, only attempts can be made to adapt the diet given to the children as best as possible to their serious health condition. For example, a low-cholesterol diet combined with cholestyramine can lead to alleviation of the effects of Wolman’s disease. The emotional and physical presence can have a positive impact on the quality of life for the affected patients. Since the parents are not given the opportunity to help their children in any other way, the focus should be on the psychological support of these. Even newborns have a very fine sense for changes in their parents’ behavior. By providing an environment that is as emotionally stable as possible, children can thus be helped to experience a time of security despite the consequences of the disease. In this regard, it is important that parents and relatives are also not afraid to accept help in caring for the child.