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Gaucher disease: Initial assessment, monitoring, and prognosis

Gaucher disease: Initial assessment, monitoring, and prognosis
Authors:
Derralynn Hughes, MD
Ellen Sidransky, MD
Section Editor:
Sihoun Hahn, MD, PhD
Deputy Editor:
Elizabeth TePas, MD, MS
Literature review current through: Jul 2022. | This topic last updated: Aug 28, 2021.

INTRODUCTION — Gaucher disease (GD) is an inborn error of metabolism that affects the recycling of cellular glycolipids. GD is one of the most common lysosomal storage diseases. Glucocerebroside (also called glucosylceramide) and several related compounds that ordinarily are degraded to glucose and lipid components accumulate within the lysosomes of cells.

GD, which often involves the visceral organs, bone marrow, and bone, is categorized into three clinical types. Type 1 (GD1, MIM #230800) is the most common. It is distinguished from type 2 (GD2, MIM #230900) and type 3 (GD3, MIM #231000) by the lack of characteristic involvement of the central nervous system (CNS).

Additional resources for information about GD for patients and caregivers are listed in the table (table 1). Guidelines for the evaluation and monitoring of children and adults with GD, based upon data from the International Collaborative Gaucher Group (ICGG) Registry and published data from international consensus panels, are incorporated into the discussion in this topic review [1-7].

The initial assessment and routine monitoring of patients with GD will be discussed here. The pathogenesis, genetics, clinical manifestations, diagnosis, and treatment are discussed separately. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis" and "Gaucher disease: Treatment".)

INITIAL ASSESSMENT — Each patient should undergo a comprehensive initial assessment of all potentially affected organ systems since there is significant variability in the manifestations, severity, and progression of GD that could impact treatment options (table 2) [8]. The initial assessment involves confirmation of deficiency of glucocerebrosidase (also known as glucosylceramidase or acid beta-glucosidase [GBA]), genotyping, and a complete family medical history if these were not part of the diagnostic process [5]. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

Many of the initial assessments are also routinely performed as part of ongoing disease monitoring (table 3). (See 'Routine monitoring' below.)

Family history — The family history should include [1,2]:

Information about ethnicity and consanguinity since GD is an autosomal-recessive disorder and certain variants are more common in specific populations. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Genetics'.)

Information about disease history in parents and/or affected siblings.

Information about Parkinson disease or Lewy body dementia in parents, grandparents, or siblings.

Information regarding a history of blood transfusions, splenectomy, pathologic fractures, bone pain, joint replacements, dyspnea, bleeding tendency, and/or perinatal deaths/hydrops fetalis. (Presence of a history of any of these could suggest undiagnosed GD in a family member and gives an overall idea of potential disease severity.)

Examination — Physical examination can provide important information regarding disease severity, rate of progression, and response to therapy [8]. Important aspects of the examination include [1,2,9]:

General appearance, demeanor, mood, and affect.

Weight, height, and head circumference percentiles, plotted on growth charts standardized for age and sex. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Growth/development' and "Measurement of growth in children".)

Examination of the skin for bruising, petechiae, pallor, and increased pigmentation. If examining a neonate, specifically look for ichthyosis. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Bone marrow disease'.)

Eye examination for pingueculae (small, soft, brownish patches of tissue on the sclerae, just beyond the iris) that are nonspecific findings sometimes seen in adult patients with GD.

The eye examination should also include evaluation for strabismus and/or abnormal extraocular movements. Additional ophthalmologic evaluation for patients who lack an N370S allele and are at risk for neuronopathic disease is discussed below. (See 'Neurologic' below.)

Palpation of the abdomen for enlarged liver and/or spleen and measurement of abdominal girth (the abdominal examination is supplemental to the radiologic evaluation). (See 'Radiology evaluation' below and "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Visceral disease'.)

Gait, range of joint motion, muscle strength, and bone tenderness. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Skeletal disease'.)

Assessment of pubertal status. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Growth/development' and "Normal puberty".)

Evaluation for developmental delay (in children). (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Presentation' and "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Type 2 (GD2)' and "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Type 3 (GD3)'.)

Examination of the spine for kyphosis (including gibbus deformity, a particular form of kyphosis with a sharp angulation) and scoliosis (image 1). (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Skeletal disease' and "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Type 3 (GD3)'.)

Neurologic — The presence of neurologic complications has important implications for prognosis and treatment and should be determined as soon as possible after diagnosis [1,2]. Thorough neurologic examination is critical for detecting evidence of neuronopathic disease in patients with suspect genotypes (ie, without an N370S allele) [9], neurologic symptoms, a sibling with proven neuronopathic GD, and/or onset of severe systemic GD before two years of age [4].

Children should undergo a thorough neurologic evaluation at baseline (table 4) [4]. This should include:

Neurologic examination performed by a neurologist, preferably a pediatric neurologist.

Eye movement examination, preferably by an ophthalmologist since the signs of ocular involvement can be difficult to detect in young children.

Additional neuroophthalmologic investigation, including direct ophthalmoscopy or electrooculography.

Measurement of hearing (by otoacoustic emission audiometry [OAE]) in young children and pure tone audiometry in older patients. (See "Hearing loss in children: Screening and evaluation".)

Electroencephalography and diagnostic brainstem-evoked responses.

Neurocognitive testing, with widely available protocols (eg, Wechsler Intelligence Scale for Children-III), ideally performed when the patient is sufficiently healthy to permit meaningful assessment.

Evaluation of swallow by fluoroscopy in very young patients with choking episodes or failure to thrive.

Audiometric testing may be helpful to evaluate brainstem disease in GD3 disease. In one study, children with this condition had abnormalities that included bilaterally increased acoustic reflexes, poor medial olivocochlear suppression, and very poor brainstem-evoked potentials [10]. Abnormalities of brainstem-evoked potential in GD3 correlated with cognitive dysfunction and disease severity in another series [11].

Psychosocial — Assessment of the child's social and educational development may require the involvement of the child's school and teachers [2]. Detailed psychometric assessments (eg, intelligence quotient [IQ] testing) should be conducted for patients at risk for developing neuronopathic disease with particular attention to verbal and performance IQ. In addition, signs of depression should be noted.

Cardiopulmonary — Cardiopulmonary involvement is rare in children with GD1 (table 5) but should be excluded at baseline in symptomatic patients [2]. Pulmonary hypertension is seen in some adults with GD1. Risk factors for severe pulmonary hypertension in patients with GD include pathogenic variants other than N370S, a family history of pulmonary hypertension, angiotensin-converting enzyme (ACE) I gene polymorphism, asplenia, and female sex [12]. Children who are compound heterozygotes and carry severe pathogenic variants such as c.84insG or IVS2+1 are more likely to have progressive pulmonary involvement. Cardiac valvular abnormalities are found in a rare subtype of GD3 associated with genotype D409H/D409H. Increased pulmonary markings are often seen on chest radiograph in other patients with GD3. This finding is associated with pulmonary infiltration of Gaucher storage macrophages and detected by reduction in transfer factor.

Evaluation in children may include chest radiograph, high-resolution computed tomography (CT) thoracic imaging, electrocardiogram, echocardiogram, and pulmonary function tests (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1] or peak expiratory flow rates [PEFR]). In adults, pulmonary evaluation should include a Doppler echocardiogram to estimate right ventricular systolic pressure [5,13]. (See "Overview of pulmonary function testing in children" and "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)".)

Laboratory evaluation — The initial laboratory evaluation should include measurement of hemoglobin concentration, platelet count, white blood cell (WBC) count, blood chemistries, liver function studies, iron studies and ferritin, thyroid function studies, and coagulation studies. Measurement of glucocerebrosidase (also known as glucosylceramidase or acid beta-glucosidase [GCase]) and genotyping of glucosylceramidase beta (GBA1) should be performed if these were not part of the diagnostic process. A serum electrophoresis and serum-free light chains should also be obtained at baseline to evaluate for clonal gammopathies in adults. Polyclonal gammopathy has also been described in children. (See 'Routine monitoring' below and 'Additional evaluation' below.)

Biochemical marker such as chemokine [C-C motif] ligand 18/pulmonary and activated-regulated chemokine (CCL18/PARC) (table 3) [2,14-17], chitotriosidase, and glucosylsphingosine can be used in monitoring disease progression [18-20]. The absolute concentrations are not helpful, but serial increases may be an early indicator of clinical relapse and should prompt investigation of disease status and compliance with therapy [21]:

Chitotriosidase, a chitinase, is a marker of "alternative" type macrophage activation that is overexpressed by the Gaucher cell. Its activity is increased in patients with GD and decreases in response to enzyme replacement therapy (ERT) in conjunction with other indicators of clinical response [14,15,22]. Measurement of chitotriosidase is recommended at baseline and periodically during therapy [23]. Activity of chitotriosidase is absent in 6 to 8 percent of patients who have a pathogenic variant in the chitotriosidase gene [8]. CCL18 can be substituted [24,25].

The chemokine CCL18/PARC is a marker of alternatively activated macrophages that is elevated in GD [24,25]. Concentrations of this protein correlate with several aspects of visceral and bony disease severity and respond to enzyme treatment in a similar manner to chitotriosidase [26,27].

Glucosylsphingosine is also elevated at diagnosis, correlates with phenotype, and declines over time with enzyme replacement [18,28]. Thus, this biomarker may be used to help determine when to initiate or modify treatment. Testing for this biomarker is now available for clinical monitoring in some centers and may ultimately replace many of the other biomarkers.

ACE and acid phosphatase are also elevated at baseline but have less utility in monitoring disease response to therapy [29]. Other biomarkers are under investigation for use in diagnosis and prediction of severity. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pathology findings'.)

Radiology evaluation — The initial radiology assessment should include various examinations to evaluate liver and spleen volume and the extent and severity of skeletal disease [1,2,5]. These studies may be helpful in determining whether ERT is indicated and are also used to monitor response to therapy. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Radiologic findings'.)

The initial radiologic evaluation may include:

Magnetic resonance imaging (MRI) or abdominal ultrasonography of the liver and spleen to help determine severity of hepatosplenomegaly and evaluate for cirrhosis, hepatic or splenic fibrosis, or the presence of focal splenic lesions, which are associated with poor platelet and splenic response to therapy [30,31]. MRI and ultrasonography are used to monitor response of hepatosplenomegaly to therapy. Volumetric CT should only be used if the other modalities are unavailable or contraindicated (eg, the patient has a pacemaker) to minimize radiation exposure [3,32].

When available, MRI of the femoral head and lumbar spine to detect bone marrow infiltration, bone infarction, bone crises, and osteonecrosis (coronal T1- and T2-weighted scan) [2,3,5]. T1-weighted MRI is the most sensitive means of assessing marrow infiltration, and T2-weighted MRI is the most sensitive method of detecting active bone infarcts.

There are several systems to grade marrow infiltration in GD, among which the Bone Marrow Burden Score is most widely used [33]. Bone marrow infiltration varies considerably from site to site within a patient [34]. A nonhomogeneous pattern of bone marrow involvement (type B marrow morphology) and extensive marrow packing were associated with avascular necrosis of the femoral head in one study, suggesting that MRI may be a useful tool for identifying patients at high risk of this outcome [35].

Determination of the skeletal age in children (according to the method of Greulich and Pyle) to assess growth [36].

Anteroposterior view of the entire femora and lateral view of the spine [37] since skeletal disease can occur without symptoms, particularly compression fractures of the spine and femoral head [3]. These radiographs will provide information regarding old fractures, cystic bone changes, osteopenia, and other bone changes, such as the Erlenmeyer flask deformity of long bones.

Radiographs of other skeletal sites to which the patient refers symptoms.

Chest radiographs, especially in children with suspected GD3.

Dual-energy x-ray absorptiometry (DXA) of the lumbar spine and nondominant femoral neck may be used to measure generalized osteopenia [37-39], although age-specific normative data for children are limited [40].

Baseline imaging (ultrasounds and routine films) is often sufficient in young children. Sedation may be necessary, though, if additional studies such as MRI or CT are required. The risk of sedation in these settings appears to be acceptably low when performed in accordance with published guidelines [41]. Nevertheless, the need for sedation limits the general applicability of MRI for routine follow-up assessment. (See "Procedural sedation in children outside of the operating room".)

Functional health and well-being — Children with GD are subject to the same psychosocial problems as any child with a chronic disease (anger, fear, insecurity, isolation) [2]. Visceromegaly, growth abnormalities, and delayed puberty may affect their body image and self-esteem. These feelings may be exacerbated by fatigue and restrictions on physical activity. Chronic pain, fatigue, and missed school may affect school performance [2]. (See 'Psychosocial' above.)

Functional health and well-being can be assessed through a survey instrument such as the short form 36 Health Survey (SF-36), which is validated for individuals ≥14 years of age [2]. Younger patients and their parents/caregivers should be questioned regarding the effects of GD on physical and social function, particularly with regard to pain and fatigue. (See "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness".)

The occurrence and severity of pain (using a recognized pain assessment tool) should be monitored at each visit [3,8]. The use of a recognized pain assessment tool is recommended [8]. In young children, pain severity may be assessed with a visual analog scale, such as the faces pain scales [42,43]. (See "Evaluation and management of pain in children" and "Evaluation of chronic non-cancer pain in adults", section on 'Pain assessment'.)

Information about GD for patients and caregivers is available through Patient Associations and other resources (table 1).

ROUTINE MONITORING — Routine monitoring of disease activity should be performed in all patients (table 3) [1,44]. The schedule is individualized according to the patient's clinical course, whether the patient is receiving treatment, and, if so, the response to therapy (table 3). Reassessment is also performed when the dose of enzyme therapy or treatment modality is changed or if significant complications develop [5]. Additional studies are recommended to monitor for other associated features, including B12 and vitamin D deficiency, iron overload, autoimmune disease, platelet dysfunction, and lipid abnormalities. Annual monitoring of protein electrophoresis and serum free light chains are recommended in adults since there is an elevated risk of myeloma. Consensus minimum recommendations for effective monitoring of patients are provided by the International Collaborative Gaucher Group (ICGG) [5]. Patients who are unable to achieve their therapeutic goals should also undergo evaluation for confounding factors (eg, poor compliance with therapy, development of comorbid conditions, or development of neutralizing antibody). (See "Gaucher disease: Treatment" and 'Initial assessment' above and 'Additional evaluation' below.)

Careful monitoring is especially important in patients who are not prescribed treatment or who refuse treatment. Aspects of the assessment that should be repeated at regular intervals throughout life include:

A complete physical examination. (See 'Examination' above.)

Close neurologic monitoring (table 6), particularly in at-risk patients (ie, children without the N370S variant or with an allele associated with neuronopathic disease), since neurologic involvement is insidious in some patients [1,3,4,45,46]. Older adults should be screened for parkinsonian manifestations. (See 'Neurologic' above.)

Measurement of hemoglobin, platelet counts, and biomarkers. (See 'Laboratory evaluation' above.)

Radiologic assessment of visceral and skeletal involvement, including magnetic resonance imaging (MRI) or abdominal ultrasonography of the liver and spleen, MRI (or radiographs if MRI is not available) of the femoral head and lumbar spine, assessment of the skeletal age in children if growth is delayed, and dual-energy x-ray absorptiometry (DXA) of the lumbar spine and nondominant femoral neck. (See 'Radiology evaluation' above.)

Assessment of pain and patient-reported quality of life. (See 'Functional health and well-being' above.)

ADDITIONAL EVALUATION — Additional evaluation may be indicated in some patients at the time of the initial assessment and/or during the clinical course depending upon the manifestation of interest or the therapeutic goal that is not achieved. A validated disease severity scoring system for GD1 in adults is available for use in monitoring intrapatient change over time [47,48].

Anemia — Additional evaluation for anemia may include measurement of iron, iron-binding capacity, vitamin B12, white blood cell (WBC) count, and serum immunoelectrophoresis. The incidence of vitamin B12 deficiency is increased among Ashkenazi Jews in Israel [49]. In addition, a decline in hemoglobin concentration, whether acute or gradual, should prompt evaluation for blood loss [8]. (See "Approach to the child with anemia" and "Diagnostic approach to anemia in adults".)

Bleeding — Patients with a history of bleeding tendency at the time of diagnosis may require evaluation for a bleeding diathesis. Abnormalities of various coagulation factors and qualitative platelet deficits have been reported in GD [5,50,51], and it may be useful to look for these abnormalities of coagulation at baseline [3,8]. Evaluation may include measure of prothrombin time (PT) and activated partial thromboplastin time (PTT) and assessment of platelet function. (See "Approach to the child with bleeding symptoms" and "Approach to the adult with a suspected bleeding disorder".)

Hepatomegaly — Evaluation of liver function is indicated in patients with marked hepatomegaly or portal hypertension. This evaluation may include assessment of exposure to alcohol, hepatotoxic medications, blood products, sexually transmitted viral pathogens, and intravenous drug use. Measurement of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), alkaline phosphatase, albumin, total protein, and total and direct bilirubin are routine in most clinical settings. Alpha-fetoprotein (AFP) levels are measured every 6 to 12 months in patients with fibrosis or other liver abnormalities to screen for hepatocellular carcinoma.

Liver imaging by ultrasound (including Doppler assessment of portal blood flow) will determine whether gross scarring and/or portal hypertension is present. Additional computed tomography (CT), magnetic resonance imaging (MRI), and liver biopsy may be necessary to reveal evidence of fibrosis or iron overload [52]. Liver stiffness values measured by transient elastography and magnetic resonance elastography were higher in splenectomized Gaucher patients [53].

Testing for viral hepatitis and/or human immunodeficiency virus (HIV) should be performed in patients who have a history of blood transfusion, intravenous or other parenteral illicit drug use, or who live in areas where infectious hepatitis is endemic [8]. (See "Epidemiology, transmission, and prevention of hepatitis B virus infection" and "Epidemiology and transmission of hepatitis C virus infection".)

Clonal gammopathies — Clonal gammopathies are frequent among patients with GD [6]. Thus, serum electrophoresis and serum-free light chain quantification should be obtained at baseline and every 12 to 24 months in adults, particularly in patients who are older than 50 years (because of an increased risk of multiple myeloma) [54].

Skeletal disease — Measurement of serum calcium, phosphorous, alkaline phosphatase, and concentrations of vitamin D and parathyroid hormone may be indicated to exclude other causes of bone disease. (See "Overview of rickets in children".)

Ischemia can be detected by technetium (Tc) bisphosphonate bone scintigraphy early in the course of bone pain crises when the changes are not yet visible on MRI [55]. Changes in (99m)Tc-sestamibi scintigraphy correlate with the main clinical features of GD [56]. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Skeletal disease' and 'Radiology evaluation' above.)

Quantitative chemical shift imaging (QCSI) measurement of bone marrow fat fraction correlates with bone complications and is sensitive to therapeutic effects of enzyme replacement [57]. However, availability of this type of imaging is limited.

Children and adolescents should be monitored for the development of scoliosis or kyphosis.

Pulmonary disease — Pulmonary involvement can be assessed by chest radiograph or pulmonary function testing. In adults, echocardiograms are recommended to screen for the development of pulmonary hypertension. In patients with GD, symptoms that could be associated with sleep apnea should prompt a sleep study. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults" and "Clinical presentation and diagnosis of obstructive sleep apnea in adults" and "Evaluation of suspected obstructive sleep apnea in children".)

Neurologic disease — Peripheral neuropathy is rarely seen in GD, and neurophysiologic assessment is required in patients who present with suggestive findings. Emergent neurologic symptoms should be evaluated for incident Parkinson disease in patients and GD carriers. (See "Overview of polyneuropathy" and "Clinical manifestations of Parkinson disease" and "Diagnosis and differential diagnosis of Parkinson disease".)

Growth retardation — Severe stunting of stature in children with GD is usually associated with severe visceral involvement [58]. Thus, other causes of growth retardation should be evaluated in otherwise mildly affected children [59]. (See "Causes of short stature".)

PROGNOSIS — The clinical course and life expectancy of GD1 is variable [8]. Severity can vary among siblings, even identical twins [60,61]. The spectrum ranges from asymptomatic disease, discovered incidentally in older adults, to fulminant disease presenting in early childhood. The disease is usually progressive but at different rates [62]. In general, the disease has rapid progression in severely affected children if left untreated but has a more insidious course in more mildly affected adults [62,63]. Thus, any rapid deterioration in adults requires evaluation for other causes. Stabilization of GD complications over time has been reported in untreated adults [64], as has spontaneous regression of disease manifestations [65]. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Type 1 (GD1)'.)

In a 2008 study based upon data from the Gaucher Registry, the estimated average life expectancy at birth for a patient with GD1 was 68 years compared with 77 years in the standard United States population [66]. However, this study included subjects from around the world, including children. Splenectomized and nonsplenectomized patients had a life expectancy of 64 years and 72 years, respectively. Prior to the treatment era, some symptomatic patients died prematurely from sequelae of splenectomy, severe bone disease, bleeding complications, infection, liver failure, or severe pulmonary disease [67]. It is likely that, for treated patients, longevity will be improved.

Asymptomatic parents and newborns with GD are often identified through prenatal and preconceptional screening. Two studies following such children have concluded that the majority have not required intervention during the first decade of life [68,69].

In addition, patients with GD appear to have an increased risk of hematologic malignancy, including plasma cell myeloma, and other malignancies, such as hepatocellular carcinoma [54,70,71]. A review of data from 2742 patients in the International Gaucher Registry (92 percent with GD1, 81 percent treated with enzyme replacement therapy [ERT], median age in the third decade) indicates that the overall risk of cancer, including general hematologic malignancies, is not increased compared with the expected rate of individuals of the same age and sex in the United States population (relative risk [RR] 0.79, 95% CI 67-94) [54]. However, the risk of plasma cell myeloma was increased (RR 5.9, 95% CI 2.9-10.8). All but one patient with multiple myeloma were older than 60 years. Multiple myeloma was reported in patients who had and had not been treated with ERT. Plasma cell myeloma should be evaluated and managed by a specialist in this condition. There is no evidence that therapy for patients with myeloma and GD should vary from best practice for plasma cell myeloma, but particular attention should be given to bone marrow recovery after chemotherapy, which is potentially aided by ongoing GD-specific therapy. (See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis".)

GD2 and GD3 are the neuronopathic forms. GD2 has the poorest prognosis of all types of GD. Patients have rapidly progressive neurologic deterioration, and death usually occurs before the child reaches two years of age. The average age of death was 11.7 months in one review of 15 original cases along with published data on 104 patients [72]. However, longevity can be increased with more aggressive therapies, although neurologic outcome remains dismal [73], with most surviving children requiring support with feeding tubes and tracheostomies. GD3 can be more severe and aggressive than GD1 but has a more variable course than GD2 [74]. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Type 2 (GD2)' and "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Type 3 (GD3)'.)

PREGNANCY — Normal pregnancies are reported in patients with GD. Pregnancy can exacerbate the symptoms of GD, particularly in females whose disease is not controlled by enzyme replacement therapy (ERT) [23]. The risks of bone crises peripartum and hemorrhage postpartum are increased. There is an emerging consensus that there are benefits to continuation of ERT in pregnancy [75,76]. This option should be discussed by the clinician and patient. (See "Gaucher disease: Treatment".)

Females with GD can generally expect a good pregnancy outcome. A literature review found 24 citations between 1952 and 2001 describing 302 pregnancies in 190 untreated females [77]. The livebirth rate was 87 percent. Postpartum bleeding was the most common serious complication (4 of 23 ERT-treated patients and 4 of 43 untreated patients). Thus, these females should be considered at high risk and evaluated prepartum. In addition, blood and coagulation advice and support should be available at delivery. (See "Overview of postpartum hemorrhage".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gaucher disease".)

SUMMARY

Gaucher disease (GD) is caused by deficiency of glucocerebrosidase (also known as glucosylceramidase or acid beta-glucosidase [GCase]), which results in abnormal accumulation of glycolipids within cellular lysosomes. (See 'Introduction' above.)

Treatment decisions must be tailored to the individual patient because of the variability in the manifestations, severity, and progression of GD. Thus, each patient should undergo a comprehensive initial assessment of all potentially affected organ systems (table 7 and table 8 and table 9). (See 'Initial assessment' above.)

The presence of neurologic complications has important implications for prognosis and treatment and should be determined as soon as possible after diagnosis. At the time of diagnosis, a through objective assessment of eye movements and audiologic testing are recommended, and all children should undergo a thorough neurologic evaluation at baseline if these specialized tests are not available. (See 'Neurologic' above.)

Routine monitoring of disease activity should be performed in all patients. The schedule is individualized according to the patient's clinical course, whether the patient is receiving treatment, and, if so, the response to therapy (table 3). In addition, reassessment should be performed when the dose of enzyme therapy is changed or if significant complications develop. (See 'Routine monitoring' above and "Gaucher disease: Treatment".)

Additional evaluation may be indicated in some patients at the time of the initial assessment and/or during the clinical course if they fail to achieve their therapeutic goals (table 7 and table 8 and table 9). The additional evaluation varies depending upon the manifestation of interest or the goal that is not achieved. (See 'Additional evaluation' above.)

The clinical course and life expectancy of GD type 1 (GD1) is variable. The estimated average life expectancy at birth for a patient with GD1 is approximately 68 years but may be increasing in the posttreatment era. In contrast, most patients with type 2 GD (GD2) die within the first years of life. GD type 3 (GD3) can be more severe and aggressive than GD1, but there is a broad spectrum of associated phenotypes. (See 'Prognosis' above.)

Pregnancy can exacerbate the symptoms of GD, particularly in females whose disease is not controlled by enzyme replacement therapy (ERT). The risks of bone crises peripartum and hemorrhage postpartum are increased. (See 'Pregnancy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Patrick Deegan, MD, MRCPI, FRCP, who contributed to an earlier version of this topic review.

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Topic 2921 Version 24.0

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