Parotid gland involvement, the presenting sign of high grade non-Hodgkin lymphoma in two patients with Gaucher disease and sicca syndrome.

Increased risk of haematological malignancies has been described in Gaucher disease patients; however, high-grade lymphoma has been rarely observed. We report two patients with Gaucher disease and sicca syndrome diagnosed with aggressive lymphoma involving the parotid gland. A 29-year-old woman with Gaucher disease developed tumour of the left parotid gland. She reported chronic arthralgias, xerostomia and xerophthalmia. Parotid gland biopsy disclosed diffuse large B-cell lymphoma. No lymphadenopathy was found. Bone biopsy revealed focal lymphomatous infiltration consistent with stage IV disease. MACOP-B chemotherapy regimen (cyclophosphamide, adriamycin, methotrexate, bleomycin, vincristine, prednisone) resulted in complete remission for 15 years. A 76-year-old patient with Gaucher disease suffered from dry-mouth feeling. He developed a left parotid gland tumour. CT scan disclosed diffuse lymphadenopathy, pleural effusion and multiple lung nodules. A cervical lymph node biopsy revealed mantle cell lymphoma. Fine-needle aspiration of the parotid gland showed lymphoma cells. Immunochemotherapy with fludarabine, cyclophosphamide and rituximab resulted in complete remission. Accumulation of the glucocerebroside in Gaucher disease activates macrophages, inducing release of pro-inflammatory cytokines which may be involved in the pathogenesis of second malignancy. Patients with Gaucher disease bear an increased risk of haematological malignancies; however, aggressive lymphoma has been described only occasionally. In both our patients the presenting sign of lymphoma was tumour of the parotid gland. The patients suffered from sicca syndrome, which increases risk for developing lymphoma. The underlying Gaucher disease and sicca syndrome might be implicated as immunological triggers for lymphoma occurrence and its propensity for the parotid gland in these patients.

Increased risk of

    haematological malignancies
    DIAGNOSIS

 has been described in

    Gaucher disease
    DIAGNOSIS

 patients; however,

    high-grade lymphoma
    DIAGNOSIS

 has been rarely observed. We report two patients with

    Gaucher disease
    DIAGNOSIS

 and

    sicca syndrome
    DIAGNOSIS

 diagnosed with

    aggressive lymphoma involving the parotid gland
    DIAGNOSIS

. A

    29-year-old
    AGE

    woman
    GENDER

 with

    Gaucher disease
    DIAGNOSIS

 developed

    tumour of the left parotid gland
    SYMPTOMS

.

    She
    GENDER

 reported

    chronic arthralgias
    SYMPTOMS

,

    xerostomia
    SYMPTOMS

 and

    xerophthalmia
    SYMPTOMS

.

    Parotid gland biopsy
    PARACLINICAL

 disclosed

    diffuse large B-cell lymphoma
    MICROSCOPIC

.

    No lymphadenopathy was found
    NEG_FINDINGS

.

    Bone biopsy
    PARACLINICAL

 revealed

    focal lymphomatous infiltration
    MICROSCOPIC

 consistent with

    stage IV disease
    DIAGNOSIS

.

    MACOP-B chemotherapy regimen (cyclophosphamide, adriamycin, methotrexate, bleomycin, vincristine, prednisone)
    MEDICATION

 resulted in

    complete remission for 15 years
    SYMPTOMS

. A

    76-year-old
    AGE

 patient with

    Gaucher disease
    DIAGNOSIS

 suffered from

    dry-mouth feeling
    SYMPTOMS

.

    He
    GENDER

 developed a

    left parotid gland tumour
    SYMPTOMS

.

    CT scan
    PARACLINICAL

 disclosed

    diffuse lymphadenopathy
    SYMPTOMS

,

    pleural effusion
    SYMPTOMS

 and

    multiple lung nodules
    SYMPTOMS

. A

    cervical lymph node biopsy
    PARACLINICAL

 revealed

    mantle cell lymphoma
    DIAGNOSIS

.

    Fine-needle aspiration of the parotid gland
    PARACLINICAL

 showed

    lymphoma cells
    MICROSCOPIC

.

    Immunochemotherapy with fludarabine, cyclophosphamide and rituximab
    MEDICATION

 resulted in

    complete remission
    MEDICATION

.

    Accumulation of the glucocerebroside in Gaucher disease
    MICROSCOPIC

    activates macrophages, inducing release of pro-inflammatory cytokines
    MICROSCOPIC

 which may be involved in the pathogenesis of

    second malignancy
    DIAGNOSIS

. Patients with

    Gaucher disease
    DIAGNOSIS

 bear an increased risk of

    haematological malignancies
    DIAGNOSIS

; however,

    aggressive lymphoma
    DIAGNOSIS

 has been described only occasionally. In both our patients the presenting sign of

    lymphoma
    DIAGNOSIS

 was

    tumour of the parotid gland
    SYMPTOMS

. The patients suffered from

    sicca syndrome
    DIAGNOSIS

, which increases risk for developing

    lymphoma
    DIAGNOSIS

. The underlying

    Gaucher disease
    DIAGNOSIS

 and

    sicca syndrome
    DIAGNOSIS

 might be implicated as immunological triggers for

    lymphoma
    SYMPTOMS

 occurrence and its propensity for the

    parotid gland
    SYMPTOMS

 in these patients.

tumour of the left parotid gland
chronic arthralgias
xerostomia
xerophthalmia
complete remission for 15 years
dry-mouth feeling
left parotid gland tumour
diffuse lymphadenopathy
pleural effusion
multiple lung nodules
tumour of the parotid gland
lymphoma
parotid gland


Type I Gaucher disease following chemotherapy for light chain multiple myeloma.

Although plasma cell disorders, such as hypergammaglobulinemia and monoclonal gammopathy of undetermined significance (MGUS), are reported to occur at higher incidences in patients with Type I Gaucher disease (GD) than in the normal population, pure light chain multiple myeloma (LCMM) has never been described in this context. Our case is the first to highlight a patient with LCMM who developed clinically apparent GD only following chemotherapy and hematopoietic stem cell transplantation. Renal complications are also exceedingly rare in GD, but nephrotic syndrome is one of the presenting features in this patient. The findings from this case will have important screening and diagnostic implications for both clinicians and patients.

Although

    plasma cell disorders
    DIAGNOSIS

, such as

    hypergammaglobulinemia
    BIOCHEMICAL

 and

    monoclonal gammopathy of undetermined significance (MGUS)
    DIAGNOSIS

, are reported to occur at higher incidences in patients with

    Type I Gaucher disease (GD)
    DIAGNOSIS

 than in the normal population,

    pure light chain multiple myeloma (LCMM)
    DIAGNOSIS

 has never been described in this context. Our case is the first to highlight a patient with

    LCMM
    DIAGNOSIS

 who developed

    clinically apparent GD
    SYMPTOMS

 only following

    chemotherapy and hematopoietic stem cell transplantation
    MEDICATION

.

    Renal complications
    SYMPTOMS

 are also exceedingly rare in

    GD
    DIAGNOSIS

, but

    nephrotic syndrome
    SYMPTOMS

 is one of the presenting features in this patient. The findings from this case will have important screening and diagnostic implications for both clinicians and patients.

clinically apparent GD
Renal complications
nephrotic syndrome


Real-time image-guided direct convective perfusion of intrinsic brainstem lesions. Technical note.

Recent preclinical studies have demonstrated that convection-enhanced delivery (CED) can be used to perfuse the brain and brainstem with therapeutic agents while simultaneously tracking their distribution using coinfusion of a surrogate magnetic resonance (MR) imaging tracer. The authors describe a technique for the successful clinical application of this drug delivery and monitoring paradigm to the brainstem. Two patients with progressive intrinsic brainstem lesions (one with Type 2 Gaucher disease and one with a diffuse pontine glioma) were treated with CED of putative therapeutic agents mixed with Gd-diethylenetriamene pentaacetic acid (DTPA). Both patients underwent frameless stereotactic placement of MR imaging-compatible outer guide-inner infusion cannulae. Using intraoperative MR imaging, accurate cannula placement was confirmed and real-time imaging during infusion clearly demonstrated progressive filling of the targeted region with the drug and Gd-DTPA infusate. Neither patient had clinical or imaging evidence of short- or long-term infusate-related toxicity. Using this technique, CED can be used to safely perfuse targeted regions of diseased brainstem with therapeutic agents. Coinfused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with a variety of intrinsic brainstem and other central nervous system disorders may benefit from a similar treatment paradigm.

Recent preclinical studies have demonstrated that

    convection-enhanced delivery (CED)
    MEDICATION

 can be used to

    perfuse the brain and brainstem with therapeutic agents
    MEDICATION

 while simultaneously tracking their distribution using

    coinfusion of a surrogate magnetic resonance (MR) imaging tracer
    PARACLINICAL

. The authors describe a technique for the successful clinical application of this drug delivery and monitoring paradigm to the brainstem. Two patients with

    progressive intrinsic brainstem lesions
    SYMPTOMS

 (one with

    Type 2 Gaucher disease
    DIAGNOSIS

 and one with a

    diffuse pontine glioma
    DIAGNOSIS

) were treated with

    CED of putative therapeutic agents mixed with Gd-diethylenetriamene pentaacetic acid (DTPA)
    MEDICATION

. Both patients underwent

    frameless stereotactic placement of MR imaging-compatible outer guide-inner infusion cannulae
    MEDICATION

. Using

    intraoperative MR imaging
    PARACLINICAL

, accurate cannula placement was confirmed and

    real-time imaging during infusion
    PARACLINICAL

 clearly demonstrated

    progressive filling of the targeted region with the drug and Gd-DTPA infusate
    MICROSCOPIC

. Neither patient had

    clinical or imaging evidence of short- or long-term infusate-related toxicity
    NEG_FINDINGS

. Using this technique,

    CED
    MEDICATION

 can be used to safely

    perfuse targeted regions of diseased brainstem with therapeutic agents
    MEDICATION

.

    Coinfused imaging surrogate tracers
    PARACLINICAL

 can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with a variety of

    intrinsic brainstem
    DIAGNOSIS

 and other

    central nervous system disorders
    DIAGNOSIS

 may benefit from a similar treatment paradigm.

Type 2 Gaucher disease
diffuse pontine glioma
intrinsic brainstem
central nervous system disorders


Treatment of Niemann-Pick disease type C in two children with miglustat: initial responses and maintenance of effects over 1 year.

Niemann-Pick disease type C (NP-C) is a lipid storage disorder characterized by the accumulation of unesterified cholesterol and glycolipids in the lysosomal/late endosomal system of certain cells in the central nervous system (CNS) and visceral organs. Clinical symptoms include progressive neurological deterioration and visceral organomegaly. Miglustat, a small iminosugar molecule approved for the treatment of Gaucher disease, reversibly inhibits glucosylceramide synthase, which catalyses the first committed step in glycosphingolipid synthesis. The physicochemical properties of miglustat allow it to cross the blood-brain barrier and suggest possible benefits in lysosomal storage diseases affecting the CNS. Here, we present findings in two children with NP-C, aged 14 years (patient 1) and 9 years (patient 2), treated with miglustat for 1 year. Before treatment, patient 1 presented with severe difficulties in swallowing and walking, and patient 2 with problems mostly affecting communication and social interaction. Videofluoroscopic studies in patient 1 demonstrated a substantial improvement in swallowing by month 6 of treatment, and ambulation index measurements indicated improved walking. Mini Mental-State Examination (MMSE) assessments in patient 2 showed cognitive improvement by month 6, which was sustained up to month 12. Liver/spleen volume and plasma chitotriosidase activities were stabilized in both cases. There was no weight loss during treatment. Patient 1 experienced severe but self-limiting paresthesia, which was not associated with peripheral neuropathy. We conclude that miglustat can provide therapeutic benefits in CNS symptoms and allows stabilization of systemic disease in childhood-onset NP-C. Further follow-up is crucial to determine the long-term maintenance of these effects.

    Niemann-Pick disease type C (NP-C)
    DIAGNOSIS

 is a

    lipid storage disorder
    DIAGNOSIS

 characterized by the

    accumulation of unesterified cholesterol and glycolipids in the lysosomal/late endosomal system of certain cells in the central nervous system (CNS) and visceral organs
    MICROSCOPIC

. Clinical symptoms include

    progressive neurological deterioration
    SYMPTOMS

 and

    visceral organomegaly
    SYMPTOMS

.

    Miglustat
    MEDICATION

, a

    small iminosugar molecule
    MEDICATION

 approved for the treatment of

    Gaucher disease
    DIAGNOSIS

,

    reversibly inhibits glucosylceramide synthase
    BIOCHEMICAL

, which catalyses the first committed step

    in glycosphingolipid synthesis
    BIOCHEMICAL

. The physicochemical properties of

    miglustat
    MEDICATION

 allow it to cross the blood-brain barrier and suggest possible benefits in

    lysosomal storage diseases affecting the CNS
    DIAGNOSIS

. Here, we present findings in two

    children
    AGE

 with

    NP-C
    DIAGNOSIS

,

    aged 14 years
    AGE

 (patient 1) and

    9 years
    AGE

 (patient 2), treated with

    miglustat for 1 year
    MEDICATION

. Before treatment, patient 1 presented with

    severe difficulties in swallowing and walking
    SYMPTOMS

, and patient 2 with

    problems mostly affecting communication and social interaction
    SYMPTOMS

.

    Videofluoroscopic studies
    PARACLINICAL

 in patient 1 demonstrated a

    substantial improvement in swallowing
    SYMPTOMS

 by month 6 of treatment, and

    ambulation index measurements
    PARACLINICAL

 indicated

    improved walking
    SYMPTOMS

.

    Mini Mental-State Examination (MMSE) assessments
    PARACLINICAL

 in patient 2 showed

    cognitive improvement
    SYMPTOMS

 by month 6, which was sustained up to month 12.

    Liver/spleen volume and plasma chitotriosidase activities were stabilized
    BIOCHEMICAL

 in both cases. There was

    no weight loss
    NEG_FINDINGS

 during treatment. Patient 1 experienced

    severe but self-limiting paresthesia
    SYMPTOMS

, which was

    not associated with peripheral neuropathy
    NEG_FINDINGS

. We conclude that

    miglustat
    MEDICATION

 can provide

    therapeutic benefits in CNS symptoms
    SYMPTOMS

 and allows

    stabilization of systemic disease
    SYMPTOMS

 in childhood-onset NP-C. Further follow-up is crucial to determine the long-term maintenance of these effects.

Miglustat
small iminosugar molecule
miglustat
miglustat for 1 year
miglustat


Gaucher disease: different clinical manifestations associated with a rare mutation (R48W) in a Lebanese family.

Gaucher disease (GD) is the most frequently encountered lysosomal storage disease, caused by autosomal recessive inborn defects in the glucocerebrosidase gene (GBA) at 1q21. The disease is most common in the Ashkenazi Jewish population. GD can present with a vast phenotypic heterogeneity, which can be predicted to some extent from the underlying mutation. In this report, we describe a Lebanese Arab family with multigenerational incidence of GD caused by a heterozygous genotype of a rare mutation, R48W, and a common one, L444P. Our patients' clinical course is described. We also review the English literature for patients with this rare mutation.

    Gaucher disease (GD)
    DIAGNOSIS

 is the most frequently encountered

    lysosomal storage disease
    DIAGNOSIS

, caused by

    autosomal recessive inborn defects in the glucocerebrosidase gene (GBA) at 1q21
    GENETICS

. The disease is most common in the

    Ashkenazi Jewish
    ETHNICITY

 population.

    GD
    DIAGNOSIS

 can present with a vast phenotypic heterogeneity, which can be predicted to some extent from the underlying mutation. In this report, we describe a

    Lebanese
    ETHNICITY

    Arab
    ETHNICITY

    family with multigenerational incidence of GD
    FAMILY

 caused by a heterozygous genotype of a rare mutation, R48W, and a common one, L444P. Our patients' clinical course is described. We also review the English literature for patients with this rare mutation.

Gaucher disease (GD)
lysosomal storage disease
GD


Pseudo-Gaucher cell proliferation associated with myelodysplastic syndrome.

We report an extremely rare case of pseudo-Gaucher cell proliferation with myelodysplastic syndrome (MDS). A 77-year old Japanese man was referred to our hospital with splenomegaly and thrombocytopenia, and subsequent bone marrow aspiration revealed infiltrates of foamy vacuolated macrophages without any evidence of other morphologic abnormalities. A karyotype analysis showed the presence of 46,XY,del(20)(q11) in 20 of 20 examined bone marrow cells. We performed a splenectomy, and the resulting pathologic findings revealed massive infiltration of foamy vacuolated macrophages, which were morphologically compatible with Gaucher cells. The activities of beta-glucosidase and acid sphingomyelinase were within normal ranges; therefore, the foamy vacuolated macrophages were considered pseudo-Gaucher cells. A diagnosis of MDS, subclassified as refractory anemia, was then made according to World Health Organization classification guidelines. Pseudo-Gaucher cell proliferation and infiltration might therefore be observed in other patients presenting with MDS.

We report an extremely rare case of

    pseudo-Gaucher cell proliferation
    MICROSCOPIC

 with

    myelodysplastic syndrome (MDS)
    DIAGNOSIS

. A

    77-year old
    AGE

    Japanese
    ETHNICITY

    man
    GENDER

 was referred to our hospital with

    splenomegaly
    SYMPTOMS

 and

    thrombocytopenia
    BIOCHEMICAL

, and subsequent

    bone marrow aspiration
    PARACLINICAL

 revealed

    infiltrates of foamy vacuolated macrophages
    MICROSCOPIC

    without any evidence of other morphologic abnormalities
    NEG_FINDINGS

. A

    karyotype analysis
    PARACLINICAL

 showed the

    presence of 46,XY,del(20)(q11) in 20 of 20 examined bone marrow cells
    GENETICS

. We performed a

    splenectomy
    MEDICATION

, and the resulting pathologic findings revealed

    massive infiltration of foamy vacuolated macrophages, which were morphologically compatible with Gaucher cells
    MICROSCOPIC

. The

    activities of beta-glucosidase and acid sphingomyelinase were within normal ranges
    NEG_FINDINGS

; therefore, the

    foamy vacuolated macrophages
    MICROSCOPIC

 were considered

    pseudo-Gaucher cells
    MICROSCOPIC

. A diagnosis of

    MDS
    DIAGNOSIS

, subclassified as

    refractory anemia
    DIAGNOSIS

, was then made according to World Health Organization classification guidelines.

    Pseudo-Gaucher cell proliferation and infiltration
    MICROSCOPIC

 might therefore be observed in other patients presenting with

    MDS
    DIAGNOSIS

.

myelodysplastic syndrome (MDS)
MDS
refractory anemia
MDS


Ultrastructural features of gaucher disease treated with enzyme replacement therapy presenting as mesenteric mass lesions.

The classical ultrastructural features of Gaucher disease include large numbers of intracytoplasmic, membrane-bound lysosomal inclusions containing characteristic tubular structures on an electron-lucent background, representing the periodic acid schiff (PAS)-positive Gaucher cells identifiable on light microscopy. Following enzyme replacement therapy (ERT), many of the manifestations of the condition are ameliorated, but persistent mesenteric lymphadenopathy has been reported, the ultrastructural features of which previously have not been described. Two children, aged 4 and 8 years old, respectively, both presented with persistent abdominal lymphadenopathy whilst receiving ERT for Gaucher disease. Needle core biopsies were carried out, that demonstrated collections of macrophages and only scattered storage-type cells on light microscopy. PAS staining was negative in one case and only focally positive in the other Electron microscopic examination, however, confirmed the cells represented macrophages, the cytoplasm of which contained scattered abnormal inclusions containing occasional twisted tubular structures of the type reported in classic Gaucher disease. ERT in Gaucher disease appears to reduce accumulation of the metabolic products at many sites. But for uncertain reasons, abdominal lymphadenopathy may occur containing macrophages that do not form granulomas or classic Gaucher cells on light microscopy. These probably represent incomplete clearance, incomplete/partial enzyme replacement, or possibly an unusual response to a relatively small amount of storage material.

The classical ultrastructural features of

    Gaucher disease
    MICROSCOPIC

 include

    large numbers of intracytoplasmic, membrane-bound lysosomal inclusions containing characteristic tubular structures on an electron-lucent background, representing the periodic acid schiff (PAS)-positive Gaucher cells
    MICROSCOPIC

 identifiable on

    light microscopy
    PARACLINICAL

. Following

    enzyme replacement therapy (ERT)
    MEDICATION

, many of the manifestations of the condition are ameliorated, but

    persistent mesenteric lymphadenopathy
    SYMPTOMS

 has been reported, the ultrastructural features of which previously have not been described. Two

    children
    AGE

,

    aged 4 and 8 years old
    AGE

, respectively, both presented with

    persistent abdominal lymphadenopathy
    SYMPTOMS

 whilst receiving

    ERT
    MEDICATION

 for

    Gaucher disease
    DIAGNOSIS

.

    Needle core biopsies
    PARACLINICAL

 were carried out, that demonstrated

    collections of macrophages and only scattered storage-type cells
    MICROSCOPIC

 on

    light microscopy
    PARACLINICAL

.

    PAS staining was negative
    NEG_FINDINGS

 in one case and only

    focally positive
    BIOCHEMICAL

 in the other

    Electron microscopic examination
    PARACLINICAL

, however, confirmed the

    cells represented macrophages, the cytoplasm of which contained scattered abnormal inclusions containing occasional twisted tubular structures of the type reported in classic Gaucher disease
    MICROSCOPIC

.

    ERT
    MEDICATION

 in

    Gaucher disease
    DIAGNOSIS

 appears to

    reduce accumulation of the metabolic products at many sites
    MICROSCOPIC

. But for uncertain reasons,

    abdominal lymphadenopathy
    SYMPTOMS

 may occur containing

    macrophages that do not form granulomas or classic Gaucher cells
    MICROSCOPIC

 on

    light microscopy
    NEG_FINDINGS

. These probably represent

    incomplete clearance
    SYMPTOMS

,

    incomplete/partial enzyme replacement
    NEG_FINDINGS

, or possibly an unusual response to a relatively small amount

    of storage material
    MICROSCOPIC

.

enzyme replacement therapy (ERT)
ERT
ERT

persistent mesenteric lymphadenopathy
persistent abdominal lymphadenopathy
abdominal lymphadenopathy
incomplete clearance

PAS staining was negative
light microscopy
incomplete/partial enzyme replacement


Neurologic improvement in a type 3 Gaucher disease patient treated with imiglucerase/miglustat combination.

Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused by a deficiency of glucocerebrosidase. The neurologic manifestations of GD patients have to date been refractory to any treatment approach. We present a report of a neuronopathic GD patient whose myoclonic epilepsy improved after combination therapy with imiglucerase and miglustat.

In an adult type 3 GD patient who, despite good visceral and analytic response to ERT, developed progressive neurologic deterioration with marked myoclonic epilepsy and dystonia, we added miglustat to the enzyme-replacement therapy.

After 2 years of combined miglustat (200 mg, 3 t.i.d.) and imiglucerase (60 IU/kg every 2 weeks), generalized tonic-clonic seizures decreased, speech improved, and the general neurologic clinical picture improved markedly. The EEG showed a reduction in focal and generalized paroxysmal discharges. No significant adverse effects were observed.

Combined imiglucerase and miglustat therapy may be beneficial for some neuronopathic forms of GD.

    Gaucher disease (GD)
    DIAGNOSIS

 is an

    autosomal recessive
    GENETICS

    lysosomal disorder
    DIAGNOSIS

 caused by a

    deficiency of glucocerebrosidase
    BIOCHEMICAL

. The

    neurologic manifestations
    SYMPTOMS

 of

    GD
    DIAGNOSIS

 patients have to date been

    refractory to any treatment approach
    NEG_FINDINGS

. We present a report of a

    neuronopathic GD
    DIAGNOSIS

 patient whose

    myoclonic epilepsy
    SYMPTOMS

 improved after

    combination therapy with imiglucerase and miglustat
    MEDICATION

.

In an

    adult
    AGE

    type 3 GD
    DIAGNOSIS

 patient who,

    despite good visceral and analytic response to ERT
    NEG_FINDINGS

, developed

    progressive neurologic deterioration
    SYMPTOMS

 with

    marked myoclonic epilepsy
    SYMPTOMS

 and

    dystonia
    SYMPTOMS

, we

    added miglustat to the enzyme-replacement therapy
    MEDICATION

.

    After 2 years of combined miglustat (200 mg, 3 t.i.d.) and imiglucerase (60 IU/kg every 2 weeks)
    MEDICATION

,

    generalized tonic-clonic seizures decreased
    SYMPTOMS

,

    speech improved
    SYMPTOMS

, and the

    general neurologic clinical picture improved markedly
    SYMPTOMS

. The EEG showed a

    reduction in focal and generalized paroxysmal discharges
    SYMPTOMS

.

    No significant adverse effects were observed
    NEG_FINDINGS

.

    Combined imiglucerase and miglustat therapy
    MEDICATION

 may be beneficial for some

    neuronopathic forms of GD
    DIAGNOSIS

.

Gaucher disease (GD)
lysosomal disorder
GD
neuronopathic GD
type 3 GD
neuronopathic forms of GD


Oral aspects of Gaucher's disease: a literature review and case report.

Gaucher's disease (GD) is a lysosomal storage disease with a high incidence in Ashkenazi Jews. The disease is caused by an autosomally recessive inherited deficiency of the lysosomal enzyme glucocerebrosidase, leading to the accumulation of glucocerebroside in macrophages. The lipid-laden macrophages, called Gaucher cells, can be detected in liver, spleen, and bone marrow tissues.

A case report of periodontal treatment of a 47-year-old female patient with GD with recurrent gingival hemorrhage and toothache is presented. Periapical radiographs revealed cyst-like lesions in the mandibular premolar-molar regions accompanied by severe apical root resorption, enlargement of the periodontal ligament and bone-marrow spaces, and loss of trabecular structure and radiopaque appearance of bone. An abnormally narrow and sharp coronoid process and effacement of the cortical borders of the mandibular canal were noted.

The patient was diagnosed as having generalized severe chronic periodontitis. Treatment included oral hygiene motivation and instructions, scaling, root planing, and access flap therapy, resulting in resolution of periodontal signs and symptoms and a marked improvement in the patient's feeling of well being.

Periodontal treatment can be effective in patients with GD. Oral findings may lead to early detection of GD, especially in the absence of clinical symptoms. Dentists should be aware of possible oral and radiographic manifestations of the disease and the role of periodontal treatment in improving patient's oral health and quality of life.

    Gaucher's disease (GD)
    DIAGNOSIS

 is a

    lysosomal storage disease
    DIAGNOSIS

 with a high incidence in

    Ashkenazi Jews
    ETHNICITY

. The disease is caused by an

    autosomally recessive inherited
    GENETICS

    deficiency of the lysosomal enzyme glucocerebrosidase
    BIOCHEMICAL

, leading to the

    accumulation of glucocerebroside in macrophages
    MICROSCOPIC

.

    The lipid-laden macrophages, called Gaucher cells, can be detected in liver, spleen, and bone marrow tissues
    MICROSCOPIC

.

A case report of

    periodontal treatment
    MEDICATION

 of a

    47-year-old
    AGE

    female
    GENDER

 patient with

    GD
    DIAGNOSIS

 with

    recurrent gingival hemorrhage
    SYMPTOMS

 and

    toothache
    SYMPTOMS

 is presented.

    Periapical radiographs
    PARACLINICAL

 revealed

    cyst-like lesions in the mandibular premolar-molar regions
    SYMPTOMS

 accompanied by

    severe apical root resorption
    SYMPTOMS

,

    enlargement of the periodontal ligament and bone-marrow spaces
    SYMPTOMS

, and

    loss of trabecular structure and radiopaque appearance of bone
    SYMPTOMS

. An

    abnormally narrow and sharp coronoid process
    SYMPTOMS

 and

    effacement of the cortical borders of the mandibular canal
    SYMPTOMS

 were noted.

The patient was diagnosed as having

    generalized severe chronic periodontitis
    DIAGNOSIS

. Treatment included

    oral hygiene motivation and instructions
    MEDICATION

,

    scaling, root planing
    MEDICATION

, and

    access flap therapy
    MEDICATION

, resulting in

    resolution of periodontal signs and symptoms
    SYMPTOMS

 and a

    marked improvement in the patient's feeling of well being
    SYMPTOMS

.

    Periodontal treatment
    MEDICATION

 can be effective in patients with

    GD
    DIAGNOSIS

.

    Oral findings
    SYMPTOMS

 may lead to early detection of

    GD
    DIAGNOSIS

, especially in the

    absence of clinical symptoms
    NEG_FINDINGS

. Dentists should be aware of possible

    oral and radiographic manifestations
    SYMPTOMS

 of the disease and the role of

    periodontal treatment
    MEDICATION

 in improving patient's oral health and quality of life.


[Morbus gaucher--a report of two cases].

[corrected] Clinical features of inherited glucocerebrosidase deficiency were first described by Phillippe Charles Ernest Gaucher, French physician (1854-1918). Deficiency of glucocerebrosidase leads to the accumulation of the lipid glucocerebroside within the lysosomes of the monocyte macrophage system. Lipid-laden cells, known as Gaucher cells, lead to hepatosplenomegaly, multiorgan dysfunction and sceletal deterioration.

We reported a 36-year-old male and a 42-year-old female admitted for the clinical examination due to hepatosplenomegaly. The Clinical diagnosis was provided by a bone marrow examination and demonstration of the characteristic Gaucher cells. Both of the patients had type I Gaucher's disease (a mild form of the disease), wich is distiguished by the lack of central nervous system involvement and striking phenotypic variation. We had not a possibility of testing beta-glucocerebrosidase activity in peripheral leukocytes (a definitive diagnosis of Gaucher's disease). Also, enzyme replacement therapy had not been available in our country.

Althoungh rare, Gaucher's disease is also present in our country. Both molecular genetic, and the enzyme beta-glucocerebrosidase activity testing in peripheral leukocytes are needed for the definitive diagnosis of this disease.

[corrected] Clinical features of

    inherited glucocerebrosidase deficiency
    GENETICS

 were first described by Phillippe Charles Ernest Gaucher, French physician (1854-1918).

    Deficiency of glucocerebrosidase
    BIOCHEMICAL

 leads to the

    accumulation of the lipid glucocerebroside within the lysosomes of the monocyte macrophage system
    MICROSCOPIC

.

    Lipid-laden cells, known as Gaucher cells
    MICROSCOPIC

, lead to

    hepatosplenomegaly
    SYMPTOMS

,

    multiorgan dysfunction
    SYMPTOMS

 and

    sceletal deterioration
    SYMPTOMS

.

We reported a

    36-year-old
    AGE

    male
    GENDER

 and a

    42-year-old
    AGE

    female
    GENDER

 admitted for the clinical examination due to

    hepatosplenomegaly
    SYMPTOMS

. The Clinical diagnosis was provided by a

    bone marrow examination
    PARACLINICAL

 and

    demonstration of the characteristic Gaucher cells
    MICROSCOPIC

. Both of the patients had

    type I Gaucher's disease
    DIAGNOSIS

 (a

    mild form of the disease)
    DIAGNOSIS

, wich is distiguished by the

    lack of central nervous system involvement
    NEG_FINDINGS

 and

    striking phenotypic variation
    SYMPTOMS

. We had

    not a possibility of testing beta-glucocerebrosidase activity in peripheral leukocytes
    NEG_FINDINGS

 (a definitive diagnosis of

    Gaucher's disease
    DIAGNOSIS

). Also,

    enzyme replacement therapy had not been available
    NEG_FINDINGS

 in our country.

Althoungh rare,

    Gaucher's disease
    DIAGNOSIS

 is also present in our country. Both

    molecular genetic,
    PARACLINICAL

 and the

    enzyme beta-glucocerebrosidase activity testing in peripheral leukocytes
    PARACLINICAL

 are needed for the definitive diagnosis of this disease.

hepatosplenomegaly
multiorgan dysfunction
sceletal deterioration
hepatosplenomegaly
striking phenotypic variation

type I Gaucher's disease
mild form of the disease)
Gaucher's disease
Gaucher's disease


Gaucher disease: progressive mesenteric and mediastinal lymphadenopathy despite enzyme therapy.

A 5-year-old male with Gaucher's disease type 3 developed progressive mesenteric and mediastinal lymphadenopathy over 12 months, despite enzyme replacement therapy, contributing to the development of a protein-losing enteropathy. These complications are unique, indicating poorly accessible, differentially responsive compartments in patients with Gaucher's disease who are receiving enzyme therapy.

A

    5-year-old
    AGE

    male
    GENDER

 with

    Gaucher's disease type 3
    DIAGNOSIS

 developed

    progressive mesenteric and mediastinal lymphadenopathy
    SYMPTOMS

    over 12 months
    SYMPTOMS

,

    despite enzyme replacement therapy
    NEG_FINDINGS

, contributing to the development of a

    protein-losing enteropathy
    BIOCHEMICAL

. These complications are unique, indicating

    poorly accessible, differentially responsive compartments
    MICROSCOPIC

 in patients with

    Gaucher's disease
    DIAGNOSIS

 who are receiving

    enzyme therapy
    MEDICATION

.

Gaucher's disease type 3
Gaucher's disease


Matched unrelated bone marrow transplantation without splenectomy for a child with Gaucher disease caused by homozygosity of the L444P mutation, who also suffered from schizencephaly.

Splenectomy followed by bone marrow transplantation (BMT) has been applied successfully in the treatment of neuronopathic Gaucher disease (GD). GD in combination with schizencephaly has not previously been reported. We describe a girl who presented with hemiparesis and oculomotor apraxia since infancy, and thereafter developed progressive anemia, thrombocytopenia, hepatosplenomegaly, psychomotor retardation, and skeletal abnormalities. GD caused by homozygosity of the L444P mutation was diagnosed, in combination with schizencephaly. The child received enzyme replacement therapy for 3 years, followed by successful matched unrelated BMT without splenectomy. The strategy of BMT without splenectomy after a period of enzyme replacement may be feasible in neuronopathic GD.

    Splenectomy followed by bone marrow transplantation (BMT)
    MEDICATION

 has been applied successfully in the treatment of

    neuronopathic Gaucher disease (GD)
    DIAGNOSIS

.

    GD in combination with schizencephaly
    DIAGNOSIS

 has not previously been reported. We describe a

    girl
    GENDER

 who presented with

    hemiparesis
    SYMPTOMS

 and

    oculomotor apraxia
    SYMPTOMS

 since

    infancy
    AGE

, and thereafter developed

    progressive anemia
    BIOCHEMICAL

,

    thrombocytopenia
    BIOCHEMICAL

,

    hepatosplenomegaly
    SYMPTOMS

,

    psychomotor retardation
    SYMPTOMS

, and

    skeletal abnormalities
    SYMPTOMS

.

    GD
    DIAGNOSIS

 caused by

    homozygosity of the L444P mutation
    GENETICS

 was diagnosed, in combination with

    schizencephaly
    DIAGNOSIS

. The

    child
    AGE

 received

    enzyme replacement therapy for 3 years
    MEDICATION

, followed by

    successful matched unrelated BMT without splenectomy
    MEDICATION

. The

    strategy of BMT without splenectomy after a period of enzyme replacement
    MEDICATION

 may be feasible in

    neuronopathic GD
    DIAGNOSIS

.

neuronopathic Gaucher disease (GD)
GD in combination with schizencephaly
GD
schizencephaly
neuronopathic GD

hemiparesis
oculomotor apraxia
hepatosplenomegaly
psychomotor retardation
skeletal abnormalities


Gaucher disease among Chinese patients: review on genotype/phenotype correlation from 29 patients and identification of novel and rare alleles.

Gaucher disease, the most prevalent lysosomal storage disease, results from an inherited deficiency in the enzyme glucocerebrosidase. Three clinical forms of Gaucher disease have been described: Type 1 non-neuronopathic, Type 2 acute neuronopathic, and Type 3 subacute neuronopathic. Although Gaucher disease is panethnic, its presentation reveals some ethnic-specific characteristics. The Type 1 form is most common among Caucasian patients. In contrast, the majority of Chinese Gaucher disease patients have early age of onset, severe hematological and skeletal complications, and often neurological involvement, resulting in early childhood death. In this report, we review 29 cases of Gaucher disease from 23 unrelated patients and 6 patients from 3 non-consanguineous families. Among these patients, 13 were diagnosed as Type 1, 10 as Type 2, and 6 as Type 3. A novel mutation, del 205-209ACCTT, was identified in the heterozygous form with mutation R353W (c.1174C>T) by DNA sequence analysis in 2 Type 1 patients who are sibs. Mutation R353W was also found in the heterozygous form in 3 other Type 1 patients, with mutation L444P in 2 sibs and a second unknown Gaucher allele in the third patient. The Gaucher genotypes of the remaining Type 1 patients were F37V/L444P, G46E/L444P, R48W/R120W, N188S/L444P, Y205C/L444P, N370S/L444P, and L444P/unknown. It was noted that mutation N370S in the patient was linked to the pv1.1(-)(1) haplotype present in Jewish patients. Among the Type 2 patients, L444P was present in the heterozygous form with mutation F213I, L385P, or the complex allele (RecNci) in 5 patients. The second most common mutation, F213I, was found in the heterozygous form in 6 patients with mutations N382K, L383R, or L444P. The other mutations found in the Type 2 patients were P122L, V375L, Y363C, M416V, and 383-400del. The genotypes of the 6 Type 3 patients identified were D409H/D409H, D409H/G202R, G46E/N188S, N188S/unknown, and L444P/L444P. While D409H has been reported as being associated with cardiovascular/ocular involvements in Gaucher disease, there have been no such complications in these patients. As noted, the majority of the Gaucher mutations we identified in the Chinese patients were either rare or absent in other populations. With the exception of N370S and R353W found only in the Type 1 form, the majority of these mutations are severe ones that result in poor prognosis and often Types 2 and 3 Gaucher disease.

    Gaucher disease
    DIAGNOSIS

, the most prevalent

    lysosomal storage disease
    DIAGNOSIS

, results from an

    inherited deficiency in the enzyme glucocerebrosidase
    GENETICS

. Three clinical forms of

    Gaucher disease
    DIAGNOSIS

 have been described:

    Type 1 non-neuronopathic
    DIAGNOSIS

,

    Type 2 acute neuronopathic
    DIAGNOSIS

, and

    Type 3 subacute neuronopathic
    DIAGNOSIS

. Although

    Gaucher disease
    DIAGNOSIS

 is

    panethnic
    ETHNICITY

, its presentation reveals some ethnic-specific characteristics. The

    Type 1 form
    DIAGNOSIS

 is most common among

    Caucasian
    ETHNICITY

 patients. In contrast, the majority of

    Chinese
    ETHNICITY

    Gaucher disease
    DIAGNOSIS

 patients have

    early age of onset
    AGE

,

    severe hematological and skeletal complications
    SYMPTOMS

, and often

    neurological involvement
    SYMPTOMS

, resulting in

    early childhood death
    AGE

. In this report, we review 29 cases of

    Gaucher disease
    DIAGNOSIS

 from 23 unrelated patients and 6 patients from 3

    non-consanguineous families
    FAMILY

. Among these patients, 13 were diagnosed as

    Type 1
    DIAGNOSIS

, 10 as

    Type 2
    DIAGNOSIS

, and 6 as

    Type 3
    DIAGNOSIS

. A

    novel mutation, del 205-209ACCTT, was identified in the heterozygous form with mutation R353W (c.1174C>T)
    GENETICS

 by

    DNA sequence analysis
    PARACLINICAL

 in 2

    Type 1 patients who are sibs
    FAMILY

.

    Mutation R353W was also found in the heterozygous form
    GENETICS

 in 3 other

    Type 1
    DIAGNOSIS

 patients

    , with mutation L444P in 2 sibs and a second unknown Gaucher allele in the third patient
    FAMILY

. The

    Gaucher genotypes
    GENETICS

 of the remaining

    Type 1
    DIAGNOSIS

 patients were

    F37V/L444P, G46E/L444P, R48W/R120W, N188S/L444P, Y205C/L444P, N370S/L444P, and L444P/unknown
    GENETICS

. It was noted that

    mutation N370S in the patient was linked to the pv1.1(-)(1) haplotype present in Jewish patients
    GENETICS

. Among the

    Type 2
    DIAGNOSIS

 patients,

    L444P was present in the heterozygous form with mutation F213I, L385P, or the complex allele (RecNci)
    GENETICS

 in 5 patients. The

    second most common mutation, F213I, was found in the heterozygous form
    GENETICS

 in 6 patients with mutations N382K, L383R, or L444P. The other mutations found in the

    Type 2
    DIAGNOSIS

 patients were

    P122L, V375L, Y363C, M416V, and 383-400del
    GENETICS

. The genotypes of the 6

    Type 3
    DIAGNOSIS

 patients identified were

    D409H/D409H, D409H/G202R, G46E/N188S, N188S/unknown
    GENETICS

, and L444P/L444P. While

    D409H
    GENETICS

 has been reported as being associated with

    cardiovascular/ocular involvements
    SYMPTOMS

 in

    Gaucher disease
    DIAGNOSIS

, there have been no such complications in these patients. As noted, the majority of the

    Gaucher mutations
    GENETICS

 we identified in the

    Chinese
    ETHNICITY

 patients were either rare or absent in other populations. With the exception of

    N370S and R353W
    GENETICS

 found only in the

    Type 1 form
    DIAGNOSIS

, the majority of these mutations are severe ones that result in poor prognosis and often

    Types 2 and 3 Gaucher disease
    DIAGNOSIS

.

Gaucher disease
lysosomal storage disease
Gaucher disease
Type 1 non-neuronopathic
Type 2 acute neuronopathic
Type 3 subacute neuronopathic
Gaucher disease
Type 1 form
Gaucher disease
Gaucher disease
Type 1
Type 2
Type 3
Type 1
Type 1
Type 2
Type 2
Type 3
Gaucher disease
Type 1 form
Types 2 and 3 Gaucher disease


Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier.

A clinical association between Gaucher disease and parkinsonism has been demonstrated. We herein report a Japanese patient with type 3 Gaucher disease who was compound heterozygous for F213I and L444P mutations in the glucocerebrosidase gene while his father was heterozygous for the L444P mutation. They both presented with parkinsonism characterized by a predominance of akinetic-rigid signs and a favorable response to anti-Parkinson therapies. We investigated the dopaminergic neuronal function using positron emission tomography (PET) with radioligands, [(11)C] CFT and [(11)C] raclopride. PET studies of both patients demonstrated the [(11)C] CFT uptake to be severely decreased in the putamen and the caudate nucleus, however, the [(11)C] raclopride uptake was normal in the basal ganglia. Although the majority of Gaucher disease patients with parkinsonism tend to be refractory to anti-Parkinson therapies. The clinical features and the findings of the PET studies suggest that patients with parkinsonism associated with the mutation in the glucocerebrosidase gene, even in heterozygosis, may be related to the presynaptic dopaminergic neuronal dysfunction reported in Parkinson's disease. A PET study to evaluate the dopaminergic neuronal function in Gaucher disease would provide both a better understanding of the effects of anti-Parkinson therapies and a help to improve our ability to make an early diagnosis of parkinsonism associated with Gaucher disease.

A clinical association between

    Gaucher disease
    DIAGNOSIS

 and

    parkinsonism
    DIAGNOSIS

 has been demonstrated. We herein report a

    Japanese
    ETHNICITY

 patient with

    type 3 Gaucher disease
    DIAGNOSIS

 who was

    compound heterozygous for F213I and L444P mutations in the glucocerebrosidase gene
    GENETICS

 while

    his
    GENDER

    father was heterozygous for the L444P mutation
    FAMILY

. They both presented with

    parkinsonism
    DIAGNOSIS

 characterized by a

    predominance of akinetic-rigid signs
    SYMPTOMS

 and a

    favorable response to anti-Parkinson therapies
    NEG_FINDINGS

. We

    investigated the dopaminergic neuronal function
    PARACLINICAL

 using

    positron emission tomography (PET) with radioligands, [(11)C] CFT and [(11)C] raclopride
    PARACLINICAL

.

    PET studies
    PARACLINICAL

 of both patients demonstrated the [(11)C

    ] CFT uptake to be severely decreased in the putamen and the caudate nucleus
    SYMPTOMS

, however,

    the [(11)C] raclopride uptake was normal in the basal ganglia
    NEG_FINDINGS

. Although the majority of

    Gaucher disease
    DIAGNOSIS

 patients with

    parkinsonism
    DIAGNOSIS

 tend to be

    refractory to anti-Parkinson therapies
    NEG_FINDINGS

. The clinical features and the findings of the

    PET studies
    PARACLINICAL

 suggest that patients with

    parkinsonism
    DIAGNOSIS

 associated with the

    mutation in the glucocerebrosidase gene
    GENETICS

,

    even in heterozygosis
    GENETICS

, may be related to the

    presynaptic dopaminergic neuronal dysfunction
    SYMPTOMS

 reported in

    Parkinson's disease
    DIAGNOSIS

. A

    PET study
    PARACLINICAL

 to

    evaluate the dopaminergic neuronal function
    PARACLINICAL

 in

    Gaucher disease
    DIAGNOSIS

 would provide both a better understanding of the effects of

    anti-Parkinson therapies
    MEDICATION

 and a help to improve our ability to make an early diagnosis of

    parkinsonism
    DIAGNOSIS

    associated with Gaucher disease
    DIAGNOSIS

.

Gaucher disease
parkinsonism
type 3 Gaucher disease
parkinsonism
Gaucher disease
parkinsonism
parkinsonism
Parkinson's disease
Gaucher disease
parkinsonism
associated with Gaucher disease


Enzyme replacement therapy in a child with Gaucher disease.

This case report describes an experience of using recombinant enzyme in a child who was diagnosed as a case of Gaucher disease at the age of 3 years. Regular enzyme replacement therapy has resulted in marked improvement in his hemoglobin level, absolute neutrophil count, platelets and physical growth.

This case report describes an experience of

    using recombinant enzyme
    MEDICATION

 in a

    child
    AGE

 who was diagnosed as a case of

    Gaucher disease
    DIAGNOSIS

    at the age of 3 years
    AGE

.

    Regular enzyme replacement therapy
    MEDICATION

 has resulted in

    marked improvement in his hemoglobin level, absolute neutrophil count, platelets and physical growth
    BIOCHEMICAL

.

using recombinant enzyme
Regular enzyme replacement therapy


Parkinsonism in type I Gaucher's disease.

The majority of patients with type I Gaucher's disease never develop neurological signs or symptoms. However, several case reports of Parkinson's disease associated with type I Gaucher's disease have been published, suggesting a genetic link between the two diseases. Hence, detailed clinical investigations are required when the two diseases occur simultaneously, in order to determine whether this is coincidental or whether a true association is present. We present a Japanese man in whom parkinsonism was associated with type I Gaucher's disease. Findings of brain positron tomography (PET) and metaiodobenzylguanidine (MIBG) cardiac scintigraphy are presented.

The majority of patients with

    type I Gaucher's disease
    DIAGNOSIS

    never develop neurological signs or symptoms
    NEG_FINDINGS

. However, several case reports of

    Parkinson's disease associated with type I Gaucher's disease
    DIAGNOSIS

 have been published, suggesting a

    genetic
    GENETICS

 link between the two diseases. Hence, detailed clinical investigations are required when the two diseases occur simultaneously, in order to determine whether this is coincidental or whether a true association is present. We present a

    Japanese
    ETHNICITY

    man
    GENDER

 in whom

    parkinsonism
    DIAGNOSIS

 was

    associated with type I Gaucher's disease
    DIAGNOSIS

. Findings of

    brain positron tomography (PET)
    PARACLINICAL

 and

    metaiodobenzylguanidine (MIBG) cardiac scintigraphy
    PARACLINICAL

 are presented.


Bone involvement in generalized crystal-storing histiocytosis.

The abnormal secretion of monoclonal immunoglobulins observed with monoclonal gammopathies and other clonal B cell dyscrasias can be responsible for a spectrum of deposition disorders. Crystal-storing histiocytosis (CSH) is a rare disease affecting patients with B cell dyscrasias and monoclonal gammopathies, characterized by the accumulation of histiocytes that have phagocytosed an abnormal crystalline immunoglobulin. We describe 2 cases of this rare disorder with multiorgan involvement and prominent bone involvement. Magnetic resonance imaging showed bone marrow infiltration and images of avascular necrosis. Bone specimen analysis gave histological proof of diffuse bone infiltration by the abnormal histiocytes. Bone involvement, which appears to be a specific feature of CSH, links this entity to other storage disorders, such as Gaucher disease. Because the accumulation of abnormal immunoglobulin-loaded histiocytes is clearly pivotal, CSH should be considered not only as an immunoglobulin deposition disease but also as a storage histiocytic disorder.

The

    abnormal secretion of monoclonal immunoglobulins
    BIOCHEMICAL

 observed with

    monoclonal gammopathies
    DIAGNOSIS

 and other

    clonal B cell dyscrasias
    DIAGNOSIS

 can be responsible for a spectrum of

    deposition disorders
    DIAGNOSIS

.

    Crystal-storing histiocytosis (CSH)
    MICROSCOPIC

 is a rare disease affecting patients with

    B cell dyscrasias
    DIAGNOSIS

 and

    monoclonal gammopathies
    DIAGNOSIS

, characterized by the

    accumulation of histiocytes that have phagocytosed an abnormal crystalline immunoglobulin
    MICROSCOPIC

. We describe 2 cases of this rare disorder with

    multiorgan involvement
    SYMPTOMS

 and

    prominent bone involvement
    SYMPTOMS

.

    Magnetic resonance imaging
    PARACLINICAL

 showed

    bone marrow infiltration
    MICROSCOPIC

 and

    images of avascular necrosis
    SYMPTOMS

.

    Bone specimen analysis
    PARACLINICAL

 gave

    histological proof
    PARACLINICAL

 of

    diffuse bone infiltration by the abnormal histiocytes
    MICROSCOPIC

.

    Bone involvement
    SYMPTOMS

, which appears to be a specific feature of

    CSH
    DIAGNOSIS

, links this entity to other

    storage disorders
    DIAGNOSIS

, such as

    Gaucher disease
    DIAGNOSIS

. Because the

    accumulation of abnormal immunoglobulin-loaded histiocytes
    MICROSCOPIC

 is clearly pivotal,

    CSH
    DIAGNOSIS

 should be considered not only as an

    immunoglobulin deposition disease
    DIAGNOSIS

 but also as a

    storage histiocytic disorder
    DIAGNOSIS

.

monoclonal gammopathies
clonal B cell dyscrasias
deposition disorders
B cell dyscrasias
monoclonal gammopathies
CSH
storage disorders
Gaucher disease
CSH
immunoglobulin deposition disease
storage histiocytic disorder

multiorgan involvement
prominent bone involvement
images of avascular necrosis
Bone involvement


Gallbladder tuberculosis: false-positive PET diagnosis of gallbladder cancer.

Gallbladder tuberculosis (GT) is an extremely rare disease, and very few cases have been reported in the literature. The first case of GT was described in 1870 by Gaucher. A correct preoperative diagnosis of GT is unusual, and it is frequently confused with various gallbladder diseases. We present a new case of a patient who underwent surgery with the preoperative diagnosis of gallbladder cancer after a false positive positron emission tomography scan in the diagnostic work-up.

    Gallbladder tuberculosis (GT)
    DIAGNOSIS

 is an extremely rare disease, and very few cases have been reported in the literature. The first case of

    GT
    DIAGNOSIS

 was described in 1870 by Gaucher. A correct preoperative diagnosis of

    GT
    DIAGNOSIS

 is unusual, and it is frequently confused with various

    gallbladder diseases
    DIAGNOSIS

. We present a new case of a patient who underwent

    surgery
    MEDICATION

 with the preoperative diagnosis of

    gallbladder cancer
    DIAGNOSIS

 after a

    false positive positron emission tomography scan in the diagnostic work-up
    NEG_FINDINGS

.

Gallbladder tuberculosis (GT)
GT
GT
gallbladder diseases
gallbladder cancer


Effective treatment of an elderly patient with Gaucher's disease and Parkinsonism: a case report of 24 months' oral substrate reduction therapy with miglustat.

We report here the results of 24 months' treatment with oral miglustat of a patient with mild-to-moderate Gaucher's disease (GD) and Parkinsonism. The patient's progressive Parkinsonian tremor, in addition to restricted vascular access, necessitated switching treatment for GD from intravenously infused enzyme replacement therapy (ERT) that had been administered for the previous 7 years. With control of haematological parameters and markers of GD activity improved or maintained and no notable adverse effects, miglustat treatment proved an effective and well-tolerated therapeutic alternative to ERT. Oral miglustat should be considered for the treatment of patients with type I GD and concurrent movement disorders who are unsuitable for ERT.

We report here the results of

    24 months' treatment with oral miglustat
    MEDICATION

 of a patient with

    mild-to-moderate Gaucher's disease (GD)
    DIAGNOSIS

 and

    Parkinsonism
    DIAGNOSIS

. The patient's

    progressive Parkinsonian tremor
    SYMPTOMS

, in addition to

    restricted vascular access
    SYMPTOMS

, necessitated

    switching treatment for GD from intravenously infused enzyme replacement therapy (ERT) that had been administered for the previous 7 years
    MEDICATION

. With

    control of haematological parameters and markers of GD activity improved or maintained
    BIOCHEMICAL

 and

    no notable adverse effects
    NEG_FINDINGS

,

    miglustat treatment
    MEDICATION

 proved an effective and well-tolerated

    therapeutic alternative to ERT
    MEDICATION

.

    Oral miglustat
    MEDICATION

 should be considered for the treatment of patients with

    type I GD
    DIAGNOSIS

 and

    concurrent movement disorders
    SYMPTOMS

 who are

    unsuitable for ERT
    NEG_FINDINGS

.

mild-to-moderate Gaucher's disease (GD)
Parkinsonism
type I GD

progressive Parkinsonian tremor
restricted vascular access
concurrent movement disorders

no notable adverse effects
unsuitable for ERT


Acute neuronopathic Gaucher disease complicated by fatal gastrointestinal bleeding.

Gaucher disease, a rare lysosomal storage disease caused by deficiency of glucocerebrosidase, may present with gastrointestinal bleeding. We report about an 11-month-old boy suffering from acute neuronopathic Gaucher disease who died after massive gastrointestinal bleeding. A gastric ulcer was found as the sole bleeding source. The gastric mucosa showed marked infiltration with Gaucher cells, in particular around the ulcer. Alterations of the gastrointestinal mucosa offer a new explanation for gastrointestinal bleedings in this disease.

    Gaucher disease
    DIAGNOSIS

, a

    rare lysosomal storage disease
    DIAGNOSIS

 caused by

    deficiency of glucocerebrosidase
    BIOCHEMICAL

, may present with

    gastrointestinal bleeding
    SYMPTOMS

. We report about an

    11-month-old
    AGE

    boy
    GENDER

 suffering from

    acute neuronopathic Gaucher disease
    DIAGNOSIS

 who

    died
    SYMPTOMS

 after

    massive gastrointestinal bleeding
    SYMPTOMS

. A

    gastric ulcer
    SYMPTOMS

 was found as the sole bleeding source. The

    gastric mucosa
    MICROSCOPIC

 showed

    marked infiltration with Gaucher cells, in particular around the ulcer
    MICROSCOPIC

.

    Alterations of the gastrointestinal mucosa
    MICROSCOPIC

 offer a new explanation for

    gastrointestinal bleedings
    SYMPTOMS

 in this disease.

Gaucher disease
rare lysosomal storage disease
acute neuronopathic Gaucher disease

gastrointestinal bleeding
died
massive gastrointestinal bleeding
gastric ulcer
gastrointestinal bleedings


Gaucher disease and multiple myeloma.

Gaucher disease (GD) is the most frequent lysosomal storage disease and corresponds to an inherited deficiency of glucocerebrosidase. Due to excessive accumulation of glucocerebroside in bone marrow, both cytopenia and bone lesions may occur. The incidence of malignant disorders has been evoked in non-neuronopathic type I GD. More particularly, many case reports have been published that describe the association between GD and multiple myeloma (MM). Here, we first deal with diagnosis criteria that allow to distinguish between bona fide Gaucher celles and the so-called pseudo or pseudo-pseudo Gaucher cells. We then analyse relevant case reports and recent articles that provide convincing data regarding GD and MM association and suggest physiopathological links between the two disorders.

    Gaucher disease (GD)
    DIAGNOSIS

 is the most frequent

    lysosomal storage disease
    DIAGNOSIS

 and corresponds to an

    inherited
    GENETICS

    deficiency of glucocerebrosidase
    BIOCHEMICAL

. Due to

    excessive accumulation of glucocerebroside in bone marrow
    MICROSCOPIC

, both

    cytopenia
    BIOCHEMICAL

 and

    bone lesions
    SYMPTOMS

 may occur. The incidence of

    malignant disorders
    DIAGNOSIS

 has been evoked in

    non-neuronopathic type I GD
    DIAGNOSIS

. More particularly, many case reports have been published that describe the

    association between GD and multiple myeloma (MM)
    DIAGNOSIS

. Here, we first deal with diagnosis criteria that allow to distinguish between

    bona fide Gaucher celles and the so-called pseudo or pseudo-pseudo Gaucher cells
    MICROSCOPIC

. We then analyse relevant case reports and recent articles that provide convincing data regarding

    GD and MM association
    DIAGNOSIS

 and suggest physiopathological links between the two disorders.

deficiency of glucocerebrosidase
cytopenia


Laparoscopic splenic autotransplantation.

Since 1990, we have performed splenic autotransplantation in more than 100 patients to treat splenic trauma, portal hypertension, myeloid metaplasia due to myelofibrosis, chronic lymphocytic leukemia, and Gaucher disease. The aim of this present study was to present splenic autotransplantation performed by laparoscopic means. A 33-year-old woman with severe splenic pain due to ischemia caused by multiple focal thromboses of splenic arterial branches was successfully treated by laparoscopic splenectomy and splenic tissue autotransplantation. The spleen was removed and cut in 20 fragments that were sutured to the greater omentum. This procedure was safely conducted with minor bleeding and no technical difficulties or complications. The postoperative follow-up of 12 months has been uneventful; the patient's pain disappeared on the first postoperative day. Hematologic, immunologic, tomographic, and scintigraphic examinations confirmed the functions of the splenic autotransplants. It is feasible and safe to perform splenic autotransplants by laparoscopic means.

Since 1990, we have performed

    splenic autotransplantation
    MEDICATION

 in more than 100 patients to treat

    splenic trauma
    SYMPTOMS

,

    portal hypertension
    DIAGNOSIS

,

    myeloid metaplasia due to myelofibrosis
    DIAGNOSIS

,

    chronic lymphocytic leukemia
    DIAGNOSIS

, and

    Gaucher disease
    DIAGNOSIS

. The aim of this present study was to present

    splenic autotransplantation
    MEDICATION

 performed by

    laparoscopic means
    MEDICATION

. A

    33-year-old
    AGE

    woman
    GENDER

 with

    severe splenic pain
    SYMPTOMS

 due to

    ischemia
    SYMPTOMS

 caused by

    multiple focal thromboses of splenic arterial branches
    SYMPTOMS

 was successfully treated by

    laparoscopic splenectomy
    MEDICATION

 and

    splenic tissue autotransplantation
    MEDICATION

. The

    spleen was removed and cut in 20 fragments that were sutured to the greater omentum
    MEDICATION

. This procedure was safely conducted with

    minor bleeding
    SYMPTOMS

 and

    no technical difficulties or complications
    NEG_FINDINGS

. The postoperative

    follow-up of 12 months
    PARACLINICAL

 has been uneventful; the patient's

    pain disappeared
    SYMPTOMS

 on the first postoperative day.

    Hematologic, immunologic, tomographic, and scintigraphic examinations
    PARACLINICAL

 confirmed the functions of the

    splenic autotransplants
    MEDICATION

. It is feasible and safe to perform

    splenic autotransplants
    MEDICATION

 by

    laparoscopic means
    MEDICATION

.

portal hypertension
myeloid metaplasia due to myelofibrosis
chronic lymphocytic leukemia
Gaucher disease


[Neurophysiolgical analysis in an 18-month-old girl with Gaucher's disease type 2].

Gaucher's disease is caused by a lack of glucocerebrosidase, and in type 2 various neurological symptoms can occur;however, the detailed pathogenesis of the condition remains undetermined. Here we performed neurophysiological examinations in an 18-month-old girl with Gaucher's disease type 2 to specify the brainstem lesions. Developmental delay occurred from the age of 8 months, and the patient subsequently showed strabismus, loss of head control, failure to thrive and irregular respiration. She was admitted to our hospital at the age of 18 months. A definite diagnosis of Gaucher's disease type 2 was made from the presence of Gaucher cells and reduced glucocerebrosidase activity. Clinically, limited ocular movements, poor facial expression and bulbar palsy indicated disturbances in the nuclei of oculomotor, trochlear, abducent, facial and ambiguous nerves, although magnetic resonance imaging (MRI) failed to visualize any structural changes in the brain including the brainstem. Neurophysiologically, auditory brainstem response and somatosensory evoked potential demonstrated lesions in the cochlear nucleus and medial lemniscus, respectively. On polysomnography, disturbed sleep parameters during rapid eye movement sleep, in addition to the lack of modification of respiratory patterns by sleep stage, suggested dysfunctions in the locus ceruleus, raphe nuclei and pontine reticular formations. It is likely that these neurophysiological tests can be useful to identify functional lesions that are not detectable by MRI, and should help exploit new treatments for child-onset neurodegenerative disorders such as Gaucher's disease.

    Gaucher's disease
    DIAGNOSIS

 is caused by a

    lack of glucocerebrosidase
    BIOCHEMICAL

, and in

    type 2
    DIAGNOSIS

 various

    neurological symptoms
    SYMPTOMS

 can occur;however, the detailed pathogenesis of the condition remains undetermined. Here we performed

    neurophysiological examinations
    PARACLINICAL

 in an

    18-month-old
    AGE

    girl
    GENDER

 with

    Gaucher's disease type 2
    DIAGNOSIS

 to specify the brainstem lesions.

    Developmental delay
    SYMPTOMS

 occurred

    from the age of 8 months
    AGE

, and the patient subsequently showed

    strabismus
    SYMPTOMS

,

    loss of head control
    SYMPTOMS

,

    failure to thrive
    SYMPTOMS

 and

    irregular respiration
    SYMPTOMS

.

    She
    GENDER

 was admitted to our hospital at the

    age of 18 months
    AGE

. A definite diagnosis of

    Gaucher's disease type 2
    DIAGNOSIS

 was made from the

    presence of Gaucher cells
    MICROSCOPIC

 and

    reduced glucocerebrosidase activity
    BIOCHEMICAL

. Clinically,

    limited ocular movements
    SYMPTOMS

,

    poor facial expression
    SYMPTOMS

 and

    bulbar palsy
    SYMPTOMS

 indicated

    disturbances in the nuclei of oculomotor, trochlear, abducent, facial and ambiguous nerves
    SYMPTOMS

, although

    magnetic resonance imaging (MRI) failed to visualize any structural changes in the brain including the brainstem
    NEG_FINDINGS

. Neurophysiologically,

    auditory brainstem response
    PARACLINICAL

 and somatosensory evoked potential demonstrated

    lesions in the cochlear nucleus and medial lemniscus
    SYMPTOMS

, respectively. On

    polysomnography
    PARACLINICAL

,

    disturbed sleep parameters during rapid eye movement sleep
    SYMPTOMS

, in addition to the

    lack of modification of respiratory patterns by sleep stage
    NEG_FINDINGS

, suggested

    dysfunctions in the locus ceruleus, raphe nuclei and pontine reticular formations
    SYMPTOMS

. It is likely that these

    neurophysiological tests
    PARACLINICAL

 can be useful to identify functional lesions that are not detectable by

    MRI
    NEG_FINDINGS

, and should help exploit new treatments for

    child-onset neurodegenerative disorders
    AGE

 such as

    Gaucher's disease
    DIAGNOSIS

.

Gaucher's disease
type 2
Gaucher's disease type 2
Gaucher's disease type 2
Gaucher's disease

lack of glucocerebrosidase
reduced glucocerebrosidase activity


Severe systemic immune response syndrome, low plasma paraoxonase activity, and a new albumin species in a traumatized patient with Gaucher's disease.

Gaucher's disease (GD) is an inborn error, autosomal recessive lysosomal lipid storage disorder characterized by the lack of the enzyme glucocerebrosidase. We observed some abnormalities in the plasma of a traumatized patient with GD.

We report of a traumatized patient with GD that developed a severe systemic immune response during the course of an extended hospital stay. Plasma paraoxonase (PON) activity was assayed and found to be extremely low possibly due to the existence of GD in this particular patient. Also, a potentially novel post-translational modification (PTM) of albumin was noticed in the patient's plasma that coincided with enzyme replacement therapy (ERT) with Cerezyme.

The decreased plasma PON activity measured might be a contributive factor in the development of an accentuated systemic immune response in a traumatized patient with GD. A modified albumin species could serve as a biomarker for ERT in Gaucher patients.

    Gaucher's disease (GD)
    DIAGNOSIS

 is an

    inborn error
    GENETICS

,

    autosomal recessive
    GENETICS

    lysosomal lipid storage disorder
    DIAGNOSIS

 characterized by the

    lack of the enzyme glucocerebrosidase
    BIOCHEMICAL

. We observed

    some abnormalities in the plasma
    BIOCHEMICAL

 of a

    traumatized
    SYMPTOMS

 patient with

    GD
    DIAGNOSIS

.

We report of a

    traumatized
    MEDICATION

 patient with

    GD
    DIAGNOSIS

 that developed a

    severe systemic immune response
    SYMPTOMS

 during the course of an

    extended hospital stay
    MEDICATION

.

    Plasma paraoxonase (PON) activity was assayed
    BIOCHEMICAL

 and found

    to be extremely low
    BIOCHEMICAL

 possibly due to the existence of

    GD
    DIAGNOSIS

 in this particular patient. Also, a

    potentially novel post-translational modification (PTM) of albumin was noticed in the
    GENETICS

 patient's plasma that coincided with

    enzyme replacement therapy (ERT) with Cerezyme
    MEDICATION

.

The

    decreased plasma PON activity measured
    BIOCHEMICAL

 might be a contributive factor in the development of an

    accentuated systemic immune response
    SYMPTOMS

 in a

    traumatized
    SYMPTOMS

 patient with

    GD
    DIAGNOSIS

. A

    modified albumin species
    BIOCHEMICAL

 could serve as a biomarker for

    ERT
    MEDICATION

 in

    Gaucher
    DIAGNOSIS

 patients.

Gaucher's disease (GD)
lysosomal lipid storage disorder
GD
GD
GD
GD
Gaucher

traumatized
severe systemic immune response
accentuated systemic immune response
traumatized


Enzyme replacement therapy with imiglucerase in a Taiwanese child with type 1 Gaucher disease.

The treatment of type 1 Gaucher disease has dramatically improved with the development of enzyme replacement therapy (ERT). To date, however, imiglucerase treatment of this disease in Taiwanese pediatric patients has not been reported. A Taiwanese child with type 1 Gaucher disease was regularly treated with imiglucerase beginning October 1998. This 12-year 10-month-old boy had undergone splenectomy when he was 4 years old. He received intravenous imiglucerase 60 U/kg every 2 weeks for 78 months. No signs of pubertal development were documented at the commencement of ERT. There were no serious adverse effects. The patient had significant improvement in skeletal deformity, a dramatic decrease in liver size, markedly increased linear growth, alleviation of bone pain and bone crises, correction of anemia, and improved bone mineral density. ERT with imiglucerase improved the quality of life in this child with type 1 Gaucher disease.

The treatment of

    type 1 Gaucher disease
    DIAGNOSIS

 has dramatically improved with the development of

    enzyme replacement therapy (ERT)
    MEDICATION

. To date, however,

    imiglucerase treatment
    MEDICATION

 of this disease in

    Taiwanese
    ETHNICITY

    pediatric
    AGE

 patients has not been reported. A

    Taiwanese
    ETHNICITY

    child
    AGE

 with

    type 1 Gaucher disease
    DIAGNOSIS

 was regularly

    treated with imiglucerase
    MEDICATION

 beginning October 1998. This

    12-year 10-month-old
    AGE

    boy
    GENDER

 had undergone

    splenectomy
    MEDICATION

 when

    he
    GENDER

    was 4 years old
    AGE

.

    He
    GENDER

 received

    intravenous imiglucerase 60 U/kg every 2 weeks for 78 months
    MEDICATION

.

    No signs of pubertal development were documented
    NEG_FINDINGS

 at the commencement of

    ERT
    MEDICATION

. There were

    no serious adverse effects
    NEG_FINDINGS

. The patient had

    significant improvement in skeletal deformity
    SYMPTOMS

, a

    dramatic decrease in liver size
    SYMPTOMS

,

    markedly increased linear growth
    SYMPTOMS

,

    alleviation of bone pain and bone crises
    SYMPTOMS

,

    correction of anemia
    BIOCHEMICAL

, and

    improved bone mineral density
    SYMPTOMS

.

    ERT with imiglucerase
    MEDICATION

 improved the quality of life in this

    child
    AGE

 with

    type 1 Gaucher disease
    DIAGNOSIS

.

type 1 Gaucher disease
type 1 Gaucher disease
type 1 Gaucher disease


Iliopsoas haematoma in Gaucher disease.

Extrapelvis or retroperitoneal haemorrhage has long been appreciated as having many causes and considerable variability in subsequent morbidity; however, to date only two cases have been reported in patients with Gaucher disease, the most common lysosomal storage disorder. It had been our assumption that these cases were unique and a consequence of severe disease in patients who had not been treated with enzyme (or other disease-specific) therapy. Herein we present three more cases (as well as our first patient), which allow one to make some generalizations. Ultrasound was used in one centre and computed tomography in the second centre to make the definitive diagnosis. The trigger for the bleeding in all cases was muscle strain after activity. All patients were young with massive hepatosplenomegaly, anaemia, thrombocytopenia, and bone pain with skeletal involvement; the last was the most obvious commonality among these patients. Differential diagnosis is complicated by exquisite groin pain that is common to both Gaucher disease and extrapelvis haemorrhage, but not necessarily.

    Extrapelvis or retroperitoneal haemorrhage
    SYMPTOMS

 has long been appreciated as having many causes and considerable variability in subsequent morbidity; however, to date only two cases have been reported in patients with

    Gaucher disease
    DIAGNOSIS

, the most common

    lysosomal storage disorder
    DIAGNOSIS

. It had been our assumption that these cases were unique and a consequence of severe disease in patients who had

    not been treated with enzyme (or other disease-specific) therapy
    NEG_FINDINGS

. Herein we present three more cases (as well as our first patient), which allow one to make some generalizations.

    Ultrasound
    PARACLINICAL

 was used in one centre and

    computed tomography
    PARACLINICAL

 in the second centre to make the definitive diagnosis. The trigger for the

    bleeding
    SYMPTOMS

 in all cases was

    muscle strain after activity
    SYMPTOMS

. All patients were

    young
    AGE

 with

    massive hepatosplenomegaly
    SYMPTOMS

,

    anaemia
    BIOCHEMICAL

,

    thrombocytopenia
    BIOCHEMICAL

, and

    bone pain with skeletal involvement
    SYMPTOMS

; the last was the most obvious commonality among these patients.

    Differential diagnosis
    PARACLINICAL

 is complicated by

    exquisite groin pain
    SYMPTOMS

 that is common to both

    Gaucher disease
    DIAGNOSIS

 and

    extrapelvis haemorrhage
    SYMPTOMS

, but not necessarily.

Gaucher disease
lysosomal storage disorder
Gaucher disease


Rheumatologic aspects of lysosomal storage diseases.

Lysosomal storage diseases are rare metabolic disorders, some of which can now be treated using enzyme replacement therapies. Because the time point of treatment initiation significantly influences the outcome in Gaucher disease, Fabry disease, and mucopolysaccharidosis type I, early diagnosis is of utmost importance. All three disorders can present with musculoskeletal symptoms in early stages, therefore, the rheumatologist may be the first to be contacted by these patients. Here, we present three characteristic lysosomal storage disease cases to increase awareness in the rheumatological community of the typical symptom constellations associated with these rare but treatable disorders.

    Lysosomal storage diseases
    DIAGNOSIS

 are

    rare metabolic disorders
    DIAGNOSIS

, some of which can now be treated using

    enzyme replacement therapies
    MEDICATION

. Because the time point of treatment initiation significantly influences the outcome in

    Gaucher disease
    DIAGNOSIS

,

    Fabry disease
    DIAGNOSIS

, and

    mucopolysaccharidosis type I
    DIAGNOSIS

, early diagnosis is of utmost importance. All three disorders can present with

    musculoskeletal symptoms
    SYMPTOMS

 in early stages, therefore, the

    rheumatologist
    PARACLINICAL

 may be the first to be contacted by these patients. Here, we present three characteristic

    lysosomal storage disease
    DIAGNOSIS

 cases to increase awareness in the rheumatological community of the typical

    symptom constellations
    SYMPTOMS

 associated with these rare but treatable disorders.

Lysosomal storage diseases
rare metabolic disorders
Gaucher disease
Fabry disease
mucopolysaccharidosis type I
lysosomal storage disease

musculoskeletal symptoms
symptom constellations


[Gaucher disease and chitotriosidase].

The course of chitotriosidase levels was studied in 4 patients with type 1 Gaucher disease during treatment or during modifications to dosage or the frequency of administration. It proved to be a good marker of disease progression, before and during treatment. In the 4 patients treated by enzyme therapy, an increase in chitotriosidase levels before treatment and then its rapid and persistent decrease after treatment initiation closely followed the efficacy of the latter. When doses were reduced, the activity of chitotriosidase made it possible to check on the persisting efficacy of treatment and to detect at an early stage any insufficient dosage or poor compliance with treatment before any clinical complications arose. During any discontinuation of treatment (e.g. for pregnancy), its assay made it possible to plan a rapid resumption of treatment if necessary. For this reason, it is useful to assay this marker before initiating any treatment, and to regularly monitor changes in its levels and concentration, notably in the event of a dosage change or increase in the interval between intakes.

The course of

    chitotriosidase levels
    BIOCHEMICAL

 was studied in 4 patients with

    type 1 Gaucher disease
    DIAGNOSIS

 during treatment or during modifications to dosage or the frequency of administration. It proved to be a good marker of disease progression, before and during treatment. In the 4 patients treated by

    enzyme therapy
    MEDICATION

, an

    increase in chitotriosidase levels
    BIOCHEMICAL

 before treatment and then

    its rapid and persistent decrease
    BIOCHEMICAL

 after treatment initiation closely followed the efficacy of the latter. When doses were reduced, the

    activity of chitotriosidase
    BIOCHEMICAL

 made it possible to check on the persisting efficacy of treatment and to detect at an early stage any

    insufficient dosage
    NEG_FINDINGS

 or

    poor compliance with treatment
    NEG_FINDINGS

 before any

    clinical complications
    SYMPTOMS

 arose. During any

    discontinuation of treatment
    MEDICATION

 (e.g. for

    pregnancy
    DIAGNOSIS

), its assay made it possible to plan a

    rapid resumption of treatment
    MEDICATION

 if necessary. For this reason, it is useful to

    assay
    PARACLINICAL

 this marker before initiating any treatment, and to regularly monitor changes in its levels and concentration, notably in the event of a

    dosage change
    MEDICATION

 or increase in the interval between intakes.

chitotriosidase levels
increase in chitotriosidase levels
its rapid and persistent decrease
activity of chitotriosidase

enzyme therapy
discontinuation of treatment
rapid resumption of treatment
dosage change

insufficient dosage
poor compliance with treatment


Type 2 Gaucher disease: 15 new cases and review of the literature.

To provide a description of type 2 Gaucher disease. To attempt to define type 2 Gaucher disease within the spectrum of early-onset neuronopathic Gaucher disease.

Type 2 Gaucher disease is a rare disorder due to glucocerebrosidase deficiency that comprises a rapidly progressing neurological degeneration associated with visceral signs. Most data collected rely on the description of single cases or siblings. Cases of perinatal-lethal Gaucher disease are frequently considered as type 2 Gaucher patients, though the clinical presentation is different.

We retrospectively studied the clinical history of 15 original acute Gaucher disease patients and reviewed the available data of 104 published cases of early-onset neuronopathic Gaucher disease, including 61 patients with the acute type and 43 cases of the perinatal-lethal form.

The neurological presentation of type 2 Gaucher disease is homogeneous and characterized by precocious, severe, and rapidly progressive brainstem degeneration in the foreground. The most frequent initial signs are hyperextension of the neck, swallowing impairment, and strabismus. Provoked asphyxic episodes generally appear in a second time. They are followed by prolonged spontaneous apneas that seem to be the main pejorative feature. Other neurological signs may be observed, but epilepsy, myoclonic epilepsy/myoclonus, trismus, stridor, and progressive microcephaly are less characteristic. Psychomotor regression may occur, but is not a typical feature of the disease onset. Chronic or subacute pulmonary disease predominates in the visceral involvement. Hepatosplenomegaly, failure to thrive, thrombocytopenia, and anemia are the other remarkable, albeit non-specific, features. The inflammatory component of Gaucher disease is underlined by the addition of unexplained fever to this systemic clinical picture. The natural history and particular signs of perinatal-lethal Gaucher disease do not belong to the type 2 Gaucher disease phenotype.

Type 2 Gaucher disease is a clinically homogeneous entity. The specificity of the neurological involvement is sufficient to suspect the diagnosis at the onset of the disease. Type 2 and perinatal-lethal Gaucher diseases are easily distinguishable in most cases.

To provide a description of

    type 2 Gaucher disease
    DIAGNOSIS

. To attempt to define

    type 2 Gaucher disease
    DIAGNOSIS

 within the spectrum of

    early-onset neuronopathic Gaucher disease
    DIAGNOSIS

.

    Type 2 Gaucher disease
    DIAGNOSIS

 is a

    rare disorder
    GENETICS

 due to

    glucocerebrosidase deficiency
    BIOCHEMICAL

 that comprises a

    rapidly progressing neurological degeneration
    SYMPTOMS

 associated with

    visceral signs
    SYMPTOMS

. Most data collected rely on the description of single cases or siblings. Cases of

    perinatal-lethal Gaucher disease
    DIAGNOSIS

 are frequently considered as

    type 2 Gaucher
    DIAGNOSIS

 patients, though the clinical presentation is different.

We retrospectively studied the clinical history of 15 original

    acute Gaucher disease
    DIAGNOSIS

 patients and reviewed the available data of 104 published cases of

    early-onset neuronopathic Gaucher disease
    DIAGNOSIS

, including 61 patients with the

    acute type
    DIAGNOSIS

 and 43 cases of the

    perinatal-lethal form
    DIAGNOSIS

.

The neurological presentation of

    type 2 Gaucher disease
    DIAGNOSIS

 is homogeneous and characterized by

    precocious, severe, and rapidly progressive brainstem degeneration in the foreground
    SYMPTOMS

. The most frequent initial signs are

    hyperextension of the neck
    SYMPTOMS

,

    swallowing impairment
    SYMPTOMS

, and

    strabismus
    SYMPTOMS

.

    Provoked asphyxic episodes
    SYMPTOMS

 generally appear in a second time. They are followed by

    prolonged spontaneous apneas
    SYMPTOMS

 that seem to be the main pejorative feature. Other

    neurological signs
    SYMPTOMS

 may be observed, but

    epilepsy
    SYMPTOMS

,

    myoclonic epilepsy/myoclonus
    SYMPTOMS

,

    trismus
    SYMPTOMS

,

    stridor
    SYMPTOMS

, and

    progressive microcephaly
    SYMPTOMS

 are less characteristic.

    Psychomotor regression
    SYMPTOMS

 may occur, but is not a typical feature of the disease onset.

    Chronic or subacute pulmonary disease
    DIAGNOSIS

 predominates in the

    visceral involvement
    SYMPTOMS

.

    Hepatosplenomegaly
    SYMPTOMS

,

    failure to thrive
    SYMPTOMS

,

    thrombocytopenia
    BIOCHEMICAL

, and

    anemia
    BIOCHEMICAL

 are the other remarkable, albeit non-specific, features. The inflammatory component of

    Gaucher disease
    DIAGNOSIS

 is underlined by the addition of

    unexplained fever
    SYMPTOMS

 to this

    systemic clinical picture
    SYMPTOMS

. The natural history and particular signs of

    perinatal-lethal Gaucher disease
    DIAGNOSIS

 do not belong to the

    type 2 Gaucher disease
    DIAGNOSIS

 phenotype.

    Type 2 Gaucher disease
    DIAGNOSIS

 is a clinically homogeneous entity. The specificity of the

    neurological involvement
    SYMPTOMS

 is sufficient to suspect the diagnosis at the onset of the disease.

    Type 2 and perinatal-lethal Gaucher diseases
    DIAGNOSIS

 are easily distinguishable in most cases.

glucocerebrosidase deficiency
thrombocytopenia
anemia


Characterization of two novel GBA mutations causing Gaucher disease that lead to aberrant RNA species by using functional splicing assays.

The correct identification of disease-causing mutations from the background of harmless nucleotide polymorphisms/substitutions has become a critical issue in the investigation of human genetic diseases. Here, we describe two novel disease-causing splicing mutations in the glucocerebrosidase gene, g.4252C>G and g.4426A>G, that have been found in two patients affected by Gaucher disease. The g.4252C>G substitution occurred in intron 5 and was located 12 nucleotides upstream of exon 6 acceptor site whilst the g.4426A>G mutation was located within this exon, 12 nucleotides upstream of the donor site. An in silico analysis suggested that both mutations could have altered the splicing process of exon 6 by creating a novel acceptor and donor site, respectively. However, because the wild-type acceptor and donor sites of exon 6 were not apparently affected, the severity of both mutations could not be established by simple sequence analysis alone. Nonetheless, the use of minigene functional assays to complement transcript analysis of patient fibroblasts shows that both mutations cause the almost complete switch of splice site usage from the wild-type to the newly-created ones, thus providing a functional explanation for the appearance of disease.

The correct identification of disease-causing mutations from the background of harmless nucleotide polymorphisms/substitutions has become a critical issue in the investigation of human

    genetic diseases
    GENETICS

. Here, we describe two

    novel disease-causing splicing mutations in the glucocerebrosidase gene, g.4252C>G and g.4426A>G
    GENETICS

, that have been found in two patients affected by

    Gaucher disease
    DIAGNOSIS

. The

    g.4252C>G substitution occurred in intron 5 and was located 12 nucleotides upstream of exon 6 acceptor site whilst the g.4426A>G mutation was located within this exon, 12 nucleotides upstream of the donor site
    GENETICS

. An

    in silico analysis
    PARACLINICAL

 suggested that both mutations could have

    altered the splicing process of exon 6 by creating a novel acceptor and donor site, respectively
    GENETICS

. However, because the

    wild-type acceptor and donor sites of exon 6 were not apparently affected
    GENETICS

, the severity of both mutations could not be established by simple sequence analysis alone. Nonetheless, the use of

    minigene functional assays to complement transcript analysis of patient fibroblasts
    PARACLINICAL

 shows that

    both mutations cause the almost complete switch of splice site usage from the wild-type to the newly-created ones
    GENETICS

, thus providing a functional explanation for the appearance of disease.


A comprehensive assessment of renal function in patients with Gaucher disease.

Gaucher disease (GD) is caused by deficiency of acid beta-glucocerebrosidase and is the most common lysosomal storage disease. Patients may have massive hepatosplenomegaly, severe bone disease, and, occasionally, pulmonary or neurological involvement. Although other storage diseases, such as Fabry disease, frequently affect the kidneys, reports of renal abnormalities in patients with GD are limited to case reports. Our aim was to perform a comprehensive evaluation of renal function in patients with GD.

Evaluation was performed at routine clinic visits and included blood pressure recording and renal ultrasound. Serum chemistries, urinalysis, urine electrolytes, total protein, and tubular proteinuria were assessed, and estimated glomerular filtration rate (GFR) was calculated.

One hundred sixty-one patients underwent evaluation, including 26 children. GFR was significantly greater in patients with GD than in age- and sex-matched healthy controls (P = 0.01 in men, P < 0.001 in women, P = 0.003 in children). Subgroups of patients with markers of more severe disease had a greater GFR than other patients. No patient had decreased renal function. Significant proteinuria was found only in patients with such comorbidities as diabetes mellitus or multiple myeloma. No evidence of renal tubular abnormalities was found, and kidney sonographic appearance and size were normal.

Despite the multiorgan nature of the disease, a systematic evaluation did not find renal abnormalities in patients with GD. Glomerular hyperfiltration was observed in a proportion of patients, particularly those with markers of more severe disease. This phenomenon does not seem to be associated with a subsequent decline in renal function.

    Gaucher disease (GD)
    DIAGNOSIS

 is caused by

    deficiency of acid beta-glucocerebrosidase
    BIOCHEMICAL

 and is the most common

    lysosomal storage disease
    DIAGNOSIS

. Patients may have

    massive hepatosplenomegaly
    SYMPTOMS

,

    severe bone disease
    SYMPTOMS

, and, occasionally,

    pulmonary or neurological involvement
    SYMPTOMS

. Although other

    storage diseases
    DIAGNOSIS

, such as

    Fabry disease
    DIAGNOSIS

, frequently affect the

    kidneys
    SYMPTOMS

, reports of

    renal abnormalities
    SYMPTOMS

 in patients with

    GD
    DIAGNOSIS

 are limited to case reports. Our aim was to perform a comprehensive

    evaluation of renal function
    PARACLINICAL

 in patients with

    GD
    DIAGNOSIS

.

Evaluation was performed at

    routine clinic visits
    PARACLINICAL

 and included

    blood pressure recording
    PARACLINICAL

 and

    renal ultrasound
    PARACLINICAL

.

    Serum chemistries, urinalysis
    PARACLINICAL

,

    urine electrolytes, total protein, and tubular proteinuria
    BIOCHEMICAL

    were assessed
    PARACLINICAL

, and

    estimated glomerular filtration rate (GFR)
    PARACLINICAL

 was calculated.

One hundred sixty-one patients underwent evaluation, including 26

    children
    AGE

.

    GFR was
    BIOCHEMICAL

 significantly greater in patients with

    GD
    DIAGNOSIS

 than in age- and sex-matched healthy controls (P = 0.01 in

    men
    GENDER

, P < 0.001 in

    women
    GENDER

, P = 0.003 in

    children
    AGE

). Subgroups of patients with markers of more severe disease had a

    greater GFR
    BIOCHEMICAL

 than other patients. No patient had

    decreased renal function
    NEG_FINDINGS

.

    Significant proteinuria
    BIOCHEMICAL

 was found only in patients with such comorbidities as

    diabetes mellitus
    DIAGNOSIS

 or

    multiple myeloma
    DIAGNOSIS

.

    No evidence of renal tubular abnormalities
    NEG_FINDINGS

 was found, and

    kidney sonographic appearance and size were normal
    NEG_FINDINGS

.

Despite the

    multiorgan
    DIAGNOSIS

 nature of the disease, a systematic evaluation did

    not find renal abnormalities
    NEG_FINDINGS

 in patients with

    GD
    DIAGNOSIS

.

    Glomerular hyperfiltration
    BIOCHEMICAL

 was observed in a proportion of patients, particularly those with markers of more severe disease. This phenomenon does not seem to be associated with a

    subsequent decline in renal function
    NEG_FINDINGS

.

Gaucher disease (GD)
lysosomal storage disease
storage diseases
Fabry disease
GD
GD
GD
diabetes mellitus
multiple myeloma
multiorgan
GD

massive hepatosplenomegaly
severe bone disease
pulmonary or neurological involvement
kidneys
renal abnormalities


Type 3 Gaucher's disease in a three-year-old child: saccadic eye movements analysis.

Gaucher's disease (GD) is an autosomal-recessive disorder that leads to the storage of sphingolipid material (glucocerebroside) in different peripheral tissues and sometimes in the central nervous system. Among its three existing forms, the most frequent non-neurological form (type 1: GD1) is treatable with appropriate amounts of exogenous enzyme-replacement therapy (ERT), whereas in the type 3 form (GD3), progression of the neurological involvement may be slowed down or halted by much higher doses of ERT than those used in GD1 because of the inability of ERT to cross the blood-brain barrier.

    Gaucher's disease (GD)
    DIAGNOSIS

 is an

    autosomal-recessive disorder
    GENETICS

 that leads to the

    storage of sphingolipid material (glucocerebroside) in different peripheral tissues and sometimes in the central nervous system
    MICROSCOPIC

. Among its three existing forms, the most frequent

    non-neurological form
    DIAGNOSIS

 (

    type 1: GD1)
    DIAGNOSIS

 is treatable with

    appropriate amounts of exogenous enzyme-replacement therapy (ERT)
    MEDICATION

, whereas in the

    type 3 form (GD3)
    DIAGNOSIS

,

    progression of the neurological involvement
    SYMPTOMS

 may be

    slowed down
    SYMPTOMS

 or halted by

    much higher doses of ERT
    MEDICATION

 than those used in

    GD1
    DIAGNOSIS

 because of the

    inability of ERT to cross the blood-brain barrier
    NEG_FINDINGS

.

Gaucher's disease (GD)
non-neurological form
type 1: GD1)
type 3 form (GD3)
GD1


Pseudo-Gaucher cells in mycobacterial infection: a report of two cases.

This report describes two cases of mycobacterial infection with pseudo-Gaucher cells. Both patients had no clinical evidence of inherited Gaucher disease. The first case was a patient with AIDS and Mycobacterium avium intracellulare involving the lung, spleen, and bone marrow. The bone marrow aspirates showed many histiocytes with needle-like inclusions. Acid fast staining showed that these histiocytes contained acid fast bacilli. Bone marrow biopsies revealed granulomatous lesions with aggregates of foamy histiocytes. The second case was an alcoholic patient with Mycobacteriumkanasassi infection involving the lung and lymph nodes. The lymph node aspirates showed infiltration of the same cells with acid fast bacilli in the cytoplasm.

This report describes two cases of

    mycobacterial infection
    DIAGNOSIS

    with pseudo-Gaucher cells
    MICROSCOPIC

. Both patients had

    no clinical evidence of inherited Gaucher disease
    NEG_FINDINGS

. The first case was a patient with

    AIDS
    DIAGNOSIS

 and

    Mycobacterium avium intracellulare
    MICROSCOPIC

    involving the lung, spleen, and bone marrow
    MICROSCOPIC

. The

    bone marrow aspirates
    PARACLINICAL

 showed

    many histiocytes with needle-like inclusions
    MICROSCOPIC

.

    Acid fast staining
    PARACLINICAL

 showed that

    these histiocytes contained acid fast bacilli
    MICROSCOPIC

.

    Bone marrow biopsies
    PARACLINICAL

 revealed

    granulomatous lesions with aggregates of foamy histiocytes
    MICROSCOPIC

. The second case was an

    alcoholic
    DIAGNOSIS

 patient with

    Mycobacteriumkanasassi infection
    DIAGNOSIS

    involving the lung and lymph nodes
    MICROSCOPIC

. The

    lymph node aspirates
    PARACLINICAL

 showed

    infiltration of the same cells with acid fast bacilli in the cytoplasm
    MICROSCOPIC

.

mycobacterial infection
AIDS
alcoholic
Mycobacteriumkanasassi infection


Uveitis in Gaucher disease.

Chronic uveitis has been previously reported in a patient with Gaucher's disease and improved with enzyme replacement therapy. This report describes the course of uveitis in two other patients with type I Gaucher's disease.

Observational case reports.

Review of all patients in a large referral clinic for Gaucher's disease for incidence of uveitis.

Two patients with uveitis among 527 patients (0.4%) were found. Each had a different clinical outcome from the other and from the patient cited in the literature.

Both patients have mild Gaucher's disease, but one patient has uveitis well controlled for 10 years solely by local corticosteroids, whereas the other has suffered progression of uveitis despite enzyme replacement therapy.

    Chronic uveitis
    DIAGNOSIS

 has been previously reported in a patient with

    Gaucher's disease
    DIAGNOSIS

 and improved with

    enzyme replacement therapy
    MEDICATION

. This report describes the course of

    uveitis
    DIAGNOSIS

 in two other patients with

    type I Gaucher's disease
    DIAGNOSIS

.

    Observational case reports
    PARACLINICAL

.

Review of all patients in a large referral clinic for

    Gaucher's disease
    DIAGNOSIS

 for incidence of

    uveitis
    DIAGNOSIS

.

Two patients with

    uveitis
    DIAGNOSIS

 among 527 patients (0.4%) were found. Each had a different clinical outcome from the other and from the patient cited in the literature.

Both patients have

    mild Gaucher's disease
    DIAGNOSIS

, but one patient has

    uveitis well controlled for 10 years
    SYMPTOMS

    solely by local corticosteroids
    NEG_FINDINGS

, whereas the other has suffered

    progression of uveitis
    NEG_FINDINGS

    despite enzyme replacement therapy
    NEG_FINDINGS

.

Chronic uveitis
Gaucher's disease
uveitis
type I Gaucher's disease
Gaucher's disease
uveitis
uveitis
mild Gaucher's disease

solely by local corticosteroids
progression of uveitis
despite enzyme replacement therapy