Imaging of non-neuronopathic Gaucher disease: recent advances in quantitative imaging and comprehensive assessment of disease involvement

Degnan, Andrew J.; Ho-Fung, Víctor; Ahrens‐Nicklas, Rebecca C.; Barrera, Christian A.; Serai, Suraj D.; Wang, Dah-Jyuu; Fıçıcıoğlu, Can

doi:10.1186/s13244-019-0743-5

Cited by 21 publications

(18 citation statements)

References 132 publications

(224 reference statements)

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“…She also had radiographic studies consistent with the diagnosis of GD. As reported in other cases, there were changes in the femoral head and femoral diaphysis that could evolve to osteonecrosis and put her at risk for pathologic fractures [23,24]. She also had classic lesions on MRI of the axial skeleton: pathologic fracture of the T3 vertebra, subtle intensity increased and compressed vertebrae, and a pseudofusion of discs between T3.…”

Section: Discussionmentioning

confidence: 56%

Difficulties in the Diagnosis of Gaucher Disease in a Low-Income Country: A Case Report from Mozambique

Pinto

Nassone

Ismail

et al. 2021

J. inborn errors metab. screen.

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Introduction: Gaucher disease (GD) is one of the common lysosomal storage disorder (LSD) with an estimated frequency of one in 40,000 newborns globally. GD is an autosomal recessive condition, which results from mutations in the GBA1 gene, causing partial or complete deficiency of β-glucocerebrosidase enzyme activity, which leads to the widespread accumulation of the substrate glucosylceramide. Aims: This report presents different challenges of clinical management and communication between medical specialties to reach diagnose of any rare disease in Mozambique, a low-income country, which health system has limited infrastructure, trained personnel, and budget for diagnosis and to provide treatment for rare genetic disorders such as GD. Case Presentation: The patient was a 15-year old black female patient of Mozambican nationality born from non-consanguineous parents. Three of the four patient's siblings were healthy; one sister had died of a disease with a similar clinical features. Our patient presented with abdominal distention and hepatosplenomegaly. Blood tests revealed pancytopenia and a high level of ferritin. Liver biopsy and histologic examination revealed infiltration of the splenic parenchyma and portal area of the liver as well as enlarged histiocytic cells with granular cytoplasm. Magnetic resonance imaging showed liver enlargement, changes in the femoral heads without osteonecrosis, a pathological fracture of the third thoracic vertebrae (T3), with absence of brain and spinal cord neurological abnormalities. The biochemical investigation disclosed low levels of β-glucocerebrosidase (0.223 nmol/h/ml; normal: above 0.98) and increased levels of lyso-Gb1 (0.43 µg/ml; normal: up to 0.003). Genotyping of the GBA1 gene indicated the presence of the pathogenic variant p.Arg87Trp (R48W) in homozygosis. Discussion and Conclusion: To the best of our knowledge, this report describes the first case of GD type 1 confirmed via biochemical and molecular genetic testing in Mozambique. As awareness of the GD and rare genetic diseases among Mozambican health professionals is very limited, and resources for diagnosis are scarce in the national health system, it is possible that other cases remain undiagnosed in this low-income country.

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Section: Discussionmentioning

confidence: 56%

Difficulties in the Diagnosis of Gaucher Disease in a Low-Income Country: A Case Report from Mozambique

Pinto

Nassone

Ismail

et al. 2021

J. inborn errors metab. screen.

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“…Although cirrhosis and portal hypertension have been regarded as rare complications in GD, there is increased risk for liver fibrosis, cirrhosis and hepatocellular carcinoma 42,43 . The exact pathophysiology of liver fibrosis in GD remains unraveled.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…42,43 The exact pathophysiology of liver fibrosis in GD remains unraveled. Hepatic infiltration by Gaucher cells might establish a fibrogenic microenvironment because of the chronic low-grade inflammation 43. In addition, immunological abnormalities, such as T-cell dysfunction or chronic stimulation of the immune system, have been implicated in the pathophysiology of liver fibrosis in GD patients.…”

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confidence: 99%

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Serum progranulin levels in paediatric patients with Gaucher disease; relation to disease severity and liver stiffness by transient elastography

Tantawy

Adly

Ismail

et al. 2020

Liver International

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Background Non‐invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis. Objectives We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE. Methods Fifty‐one GD patients (20 had type 1 and 31 had type 3) with a median age of 9.5 years were compared to 40 age‐ and sex‐matched healthy controls and were studied focusing on visceral manifestations, neurological disease, haematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients were on enzyme replacement therapy (ERT) for various durations and those with viral hepatitis infection were excluded. Results By TE, 14 GD patients (27.5%) had elevated liver stiffness ≥7.0 kPa. Liver stiffness was significantly higher in type 1 GD patients than type 3 (P = .002), in splenectomized patients (P = .012) and those with dysphagia (P < .001). Liver stiffness was positively correlated with age of onset of ERT (P < .001). PGRN levels were significantly lower in GD patients compared with controls (P < .001). PGRN was significantly lower in GD patients with squint (P = .025), dysphagia (P = .036) and elevated liver stiffness (P = .015). PGRN was positively correlated with white blood cell count (r = .455, P = .002) and haemoglobin (r = .546, P < .001), while negatively correlated with severity score index (r = −.529, P < .001), liver volume (r = −.298, P = .034) and liver stiffness (r = −.652, P < .001). Conclusions Serum PGRN levels were associated with clinical disease severity and elevated liver stiffness in paediatric GD patients.

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“…An ultrasound examination has been traditionally used to monitor development of cirrhotic morphology but is relatively insensitive in detecting earlier fibrotic changes. Some means of noninvasively assessing hepatic fibrosis include non-imaging-based transient elastography (TE), ultrasound shear wave elastography (SWE), and magnetic resonance elastography (MRE) [17]. The disease specific management of GD includes enzyme replacement therapy (ERT) and substrate reduction therapy (SRT).…”

Section: Discussionmentioning

confidence: 99%

Gaucher Disease: A Rare Case in Children with Malignancy-Like Manifestation

Setiyawan¹,

Sidiartha²,

Pratiwi³

2020

IJGG

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Gaucher Disease (GD) is an autosomal recessive systemic lysosomal storage disorder which is characterized by glucocerebroside deposition in cells of the macrophage-monocyte system as a result of a deficiency in lysosomal glycosidase (glucocerebrosidase). The high prevalence of symptomatic hepatosplenomegaly and thrombocytopenia in GD commonly lead patients to present to haematologists. The time period from onset of symptoms to diagnosis remains prolonged and patients are still predominately diagnosed by bone marrow biopsy. This is a case of a 4-years-old boy who presented with weakness, pallor, and gradually increasing abdominal girth. At first the patient was suspected as an abnormality in hematooncology field (acute leukemia) due to the results of the laboratories that revealed pancytopenia and the presence of organomegaly. After bone marrow aspiration examination conducted the result was not in accordance in the field of hematooncology. Final diagnosis of GD was established after reevaluating the bone marrow smears that find foam cells/Gaucher cells. Confirmation of diagnosis on Gaucher disease was performed by measurement of glucocerebrosidase activity, where is low in β-Glucosidase 0.07 uM/hr (reference range unit >1.8 uM/hr). GD should be considered in the differential diagnosis of children with unexplained hepatosplenomegaly. Patients with acute leukemia suspicion should be examined for the possibility of having GD from bone marrow smears simultaneously. Moreover, the early recognition of GD would lead to safe and effective treatment with enzyme replacement which can decrease morbidity.

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Imaging of non-neuronopathic Gaucher disease: recent advances in quantitative imaging and comprehensive assessment of disease involvement

Cited by 21 publications

References 132 publications

Difficulties in the Diagnosis of Gaucher Disease in a Low-Income Country: A Case Report from Mozambique

Difficulties in the Diagnosis of Gaucher Disease in a Low-Income Country: A Case Report from Mozambique

Serum progranulin levels in paediatric patients with Gaucher disease; relation to disease severity and liver stiffness by transient elastography

Gaucher Disease: A Rare Case in Children with Malignancy-Like Manifestation

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