Introduction

Lysosomal Storage Diseases (LSDs) count numerous inherited metabolic diseases.¹ In this classification, Gaucher Disease is the most prominent. Indeed, the enzyme mutation responsible for the disease is the glucocerebrosidase  (GBA) gene.¹ The new enzyme is defective. For the transmission, both parents must have one gene with mutations. The non-functional enzyme will allow an accumulation of glucosylceramide and some other toxic substrates^1,2 in the body cells. Blood cells as macrophages, leukocytes store those components in a particular cellular site named: Lysosome. Many organs are concerned by the storage:^2,3

• Bone marrow
• Liver
• Spleen
• Reticuloendothelial system

Chronic storage will have many consequences. This state can promote emotional vulnerability in the patient and their caregivers. Some studies^4,5,6 have shown that patients and their entourage, have a mental component in quality of life score a half lower than the general population. So mental health is a main subject in the treatment of Gaucher disease.

Overview of gaucher disease

Prevalence and demographic information

In 2021, the global birth prevalence of the GD was 1,5 cases per 100,000 live births.⁷ The incidence is historically higher in the Ashkenazi Jewish population, at approximately 1 in 1,000.^3,2

Mode of transmission

As an autosomal recessive transmission, the disease can affect both genders. The specificity of GBA mutations will allow sizable presentations of the disease.¹

Symptoms and signs

The first manifestations could appear early in childhood to the seventh decade.² Nevertheless, 2/3 are diagnosed under the age of 20 years.^4,5

There are three features of Gaucher disease. The classification is made regarding neurologic involvement.² Type I did not have neurologic involvement. Fortunately, it counts above 90% of  Gaucher Disease cases. Type II and type III both have neurologic symptomatology.¹

Fig. 1. Timeline of presenting signs and symptoms of GD throughout childhood and details of other childhood diseases with overlapping signs and symptoms.⁸

Gaucher type I

The signs here are less severe. Patients could face a cognitive regression evolving slowly in adolescence or early at adult age².

Gaucher type II or acute neuropathic disease²

This is the most lethal form. GD type II evolves rapidly to total impairment and death in 2 years after birth. The embryonic form of GD  can result in fetal death or numerous disorders². As clinical manifestations, we have:

• In general state, we have Retardation of development; the baby gains no or little weight 
• Neurologic manifestation: seizures; the child’s head leans back; palsy of some eye  muscles (horizontal plan); the child doesn’t move properly because increasing muscle tonus leading to tightness or stiffness(spasticity)⁹ or a general posterior muscle contraction² of the body call opisthotonos; the bilateral adduction and infolding of thumbs; other signs of motor neuron damages in the cerebral cortex
• Osteoarticular sign: bone pain

Gaucher disease type III or chronic neuropathic disease 

Evolution is more insidious. Generally, patients could have in addition to those above: hearing loss; eye misalignment

At the physical examination:²

1. Hepatosplenomegaly: augmentation of the height of the spleen and the liver
2. Anaemia signs as pallor
3. Neurologic examination is disturbed with a hypertonicity

Diagnostic

Many exams have to be performed as follows:^2,8

• Radiography: will show bone disease as marrow infiltration, osteopenia, Erlenmeyer flask deformity of the femur; avascular necrosis, pathologic fractures, lytic lesions
• Blood count: we see anaemia, thrombocytopenia,
• Biochemistry analysis: Measurement of the glucocerebrosidase enzyme activity in Leukocytes
• Genetic test: identification of two pathogenic variants in the GBA gene
• Biopsy of the bone marrow: reveals a special pattern as a sprained tissue paper

Treatment^2,4,5,6,8

The treatment available for the moment doesn’t act on the neurodegenerative conditions. It helps with a better impact on hematologic and visceral parameters.

It depends on the different types as follows:

Type I and III

Enzyme recovery therapy(ERT)

FDA approved three enzyme replacement therapies (ERT) that act as functional enzymes to treat patients with significant splenomegaly, eliminating the need for splenectomy. These therapies include.

• Imiglucerase(Cerezyme)
• Velaglucerase alfa(VPRIV)
• Taliglucerase alfa(Elelyso) is only for adult

Substrate reduction therapy(SRT)

Currently, two therapies are approved by the FDA. Her active principle is to inhibit the enzyme named glucosylceramide synthase which will reduce the percentage of the nonfunctional glucosylceramide.² We have:

• Miglustat(Zavesca) only for adult
• Eliglustat(Cerdelga) is only for adult

In practice, most patients begin with ERT and then they transition at an old age to SRT which can be taken orally.

Type II

Currently, there is no specific therapy for Gaucher Disease type II. The management is primarily symptomatic focusing on nutritional support due to neurodegenerative conditions and respiratory support.

Complications^1,2,8

Because it is a chronic disease, in evolution we could have some complications  as

• Acute bone crisis: which can be relieved by high-dose steroids.
• Malignancy(particularly the multiple myeloma)
• Pulmonary diseases such as pulmonary arterial hypertension  and hepatopulmonary syndrome

Prognostic

It will depend on many points as the type of

• Specificity of the mutation
• The type of Gaucher disease. The type II is the most severe.
• The rapidity of the diagnosis: The faster the diagnosis is done, the more probable complications could be avoided.
• Access to healthcare and drugs

Monitoring¹

Throughout life, depending on the progression of neurologic involvement and treatment status, the patients may undergo annual assessments. Some physicians recommend as following:

• IRM at regular intervals to monitor the spleen and liver
• IRM of spine and femur for bone assessment
• Abdominal ultrasound
• Assessments of emotional well-being through various surveys

Life expectancy⁷

Over the years, life expectancy has increased, rising from 66.8 years in 2000 to 74.6 years in 2019. Life expectancy also varies depending on healthcare policies and practices in each country.

Emotional response^4,5,6

Medical care in GD has to be holistic. In fact, in addition to clinical signs, physicians have to pay attention to emotional states. The psychological stress has to be assessed by both the patient himself and the family caregivers and the patient himself. The mental health of patients with GD or caregivers correlates with the severity of the clinical state. Naturally, the Gaucher type II is the most stressful. 

How can physicians assess your emotional state?

• Quality of life (QoL) survey which usually has the mental item
• Assessment of the pain and its management by anti-inflammatory and antidepressant drugs¹

How does Gaucher's disease impact emotional well-being?

In  patients

• Diagnostic wandering with a long time of the confirmation of the disease above with a maximum of 6.6 years⁶
• Impact of pain⁶
• Disturbance of the Career and recreational activity⁶
• Uncertainty about the future

In caregivers

• Insufficiency education for basic healthcare
• Misunderstanding of Gaucher disease and the evolution (future) of the illness
•  Burdens for access to healthcare services: due to problematic availability of therapeutic drugs. The drugs are expensive. They are also still not available in every country, or region of the country.
• The interruption of the work or change of the weekly work  schedule  and absenteeism
• Loss of the productivity of caregivers and early retirement
• Lower social support: from other family members; from the administration; from the insurance which does not cover every healthcare.
• Daily care time could be high. Some family caregivers report more than 6 hours per day

How to prevent emotional well-being in gaucher disease?

Primary prevention of mental health

Before diagnosis

Government

• Improve the access to market authorization(approval)  to countries for imported orphan drugs^{4 ,5,6}
• Allocate more budget for research in Gaucher disease by promoting the” development and supply” of generic drugs^{4 ,5,6}
• Increase the point of sale of medicines
• Increase the reimbursement for every orphan drug therapy With a low out-of-pocket payment^{4 ,5,6}

Health Insurance companies

Health insurance companies could offer specialized coverage plans tailored for patients with Gaucher disease.

Physicians

• Knowledge about GD to avoid misdiagnosis and delay in treatment which cause psychological stress
• Need for Systematic genetic screening for patients with a family history of GD especially in newborns (Ashkenazi Jewish)

Family members

• Awareness while choosing a life partner if a genetic disorder exists in the family
• Build strong associations which can do fundraising for research

Secondary prevention^4,5,6

It Is done when the Gaucher disease already affects the mental health

Governmental action

• Promote the development of a good network of Orhan patients: a space of listening and exchange
• Sitting up  a national database for good monitoring and communication of every patient

Physician and psychological help

• Provide objective support
• Give appropriate nursing suggestions, particularly with type II patients

Patient and caregivers

• Take the effective treatment correctly 
• Have good monitoring: to improve health and escape from complications.
• Have a good nutrition
• Be surrounded by  Positive people

Summary

Through the years, many efforts have been made for a better understanding of Gaucher Disease and its implications on patient's and caregiver's lives. Indeed, in addition to clinical examination, an emotional assessment appears also important. Emotional problems are mainly due to the severity of the clinical state, diagnostic wandering, economic issues, and the lack of social and governmental support.

All those things lead to a poor emotional state. To solve that, everybody can play a crucial role. The Government and insurance must facilitate the affordability of drugs and health care. Physicians and other healthcare professionals need more training on Gaucher's disease. Finally, the family and caregivers have good training on the information to be more useful for the patients. Indeed, it is a collaborative multidisciplinary effort.