Currently, there are an estimated 6000–8000 rare diseases, which affect 350 million people worldwide.1 One such rare condition is Gaucher Disease (GD) – a lysosomal storage disorder (LSD). GD is a rare genetic disorder, passed down from parents to children (inherited) in an autosomal recessive manner.
GD is one of the most common LSDs with a prevalence in the general population of ~1 per 100 000 and ~1/855 in the Ashkenazi Jewish population.2 As with many rare conditions, diagnosis of GD may present a significant challenge to non-GD specialities, owing to the wide variability in age, severity, type of clinical manifestation and lack of awareness of the early signs and symptoms of GD among non-specialist physicians.3 One in 6 patients with GD reported a diagnosis delay of 7 years or more after first consulting a doctor.3
International Gaucher Day on 1 October, therefore, aims to improve patients’ quality of life through greater awareness and earlier diagnosis of GD amongst healthcare professionals.
GD arises from an inherited deficiency of an enzyme called glucocerebrosidase, normally found within the lysosomes of cells, due to mutations in the GBA gene.4 This enzyme is responsible for breaking down a fatty substrate, glucocerebroside, into glucose and a simpler fat molecule (ceramide).4 Patients with GD have a progressive build-up of glucocerebroside within the lysosomes, particularly of macrophages, resulting in enlarged cells known as ‘Gaucher’ cells.4
These ‘Gaucher’ cells accumulate in organs throughout the body, predominately affecting the bone marrow, liver, and spleen.4 There are three types of GD, based on the presence and severity of neurological involvement.4 Type 1, known as the non-neuronopathic GD characterised by haematological abnormalities such as thrombocytopenia, leukopenia and anaemia, hepatomegaly and/or splenomegaly, bone crises and/or osteoporosis, and fatigue.4 Phenotypically, there is a wide spectrum of disease manifestations, ranging from asymptomatic to severe type 1 child-onset disease.5,6 Type 2, the acute neuronopathic form, is the rarest and most severe form of GD. It includes the rapid progression of severe neurological abnormalities early in life, leading to death in infancy or early childhood.4,6 Type 3, the chronic form, encompasses multiple phenotypes. Type 3 typically occurs during the paediatric years and varies in severity: patients have the same symptoms as in type 1, plus some neurological involvement that generally appear later in life, such as abnormal eye movement, ataxia, seizures and dementia.4
Anaemia, thrombocytopenia, enlargement of the liver and/or spleen, and skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of type 1 GD, the most prevalent form of the disease.5 However, the severity and coexistence of different symptoms are highly variable, and GD patients are often misdiagnosed as having other malignant haematological conditions.4
Although GD is rare, clinicians are encouraged to maintain a high index of suspicion with patients presenting with atypical symptoms, and should consider testing for rare diseases where other haematological pathologies have been excluded4 or when testing for them. Such patients may be referred to a GD specialist or be tested through North West University (NWU), where global pharmaceutical company Sanofi and the NWU Centre of Human Metabolomics, headed by Prof Chris Vorster, have partnered to test for the most common lysosomal storage disorders in South Africa, including GD, using dried blood spot samples.
Says Prof. Vorster: “Rare conditions such as GD require the cooperation of a multidisciplinary team in order to find and treat them. Interventions can improve a patient’s quality of life through improvement or restoration of their physical function, so that they may carry out regular daily activities. The NWU Centre of Human Metabolomics provides internationally competitive metabolomic analytic services, and electronic results may be sent by high priority straight to healthcare practitioners, speeding up diagnosis.”
Monique Nel, Medical Advisor – Rare Diseases at Sanofi, says: “We understand the difficulty that healthcare professionals face when it comes to diagnosing patient with GD. It requires a coordinated approach to diagnosis and care for people living with the condition. Early diagnosis of GD, and the initiation of treatment will delay the occurrence of irreversible complications, and improve the patient’s quality of life. We therefore direct the attention of healthcare providers to the RD Nexus platform, which is Sanofi’s dedicated platform for rare diseases, at www.RDNexus.com. This platform offers educational materials, road maps to a differential diagnosis and how to test a patient for these conditions.”
For more information on GD and other rare diseases, visit: www.RDNexus.com
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505568/pdf/EMMM-11-e10486.pdf Accessed September 2022.
- Burrow TA et al. Prevalence and management of Gaucher disease. Paediatric Health, Medicine and Theraeutics 2011;2:59-73.
- Revel-Wilk S, et al. How we manage Gaucher Disease in the era of choices. British Journal of Haematology 2018;182:467-480.
- CPD Gaucher. Gaucher Disease. Medical Chronicle June 2020:30-32.
- Linari S, Castaman G. Clinical manifestations and management of Gaucher disease. Clinical Cases in Mineral and Bone Metabolism 2015;12(2):157-164.
- Roshan Lal T and Sidransky E. The spectrum of neurological manifestations associated with Gaucher Disease. Diseases 2017;5,10.
