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Answer to the case of the week # 118

May 7-20, 2004

Luc Gourand, MD*, Irene Maire, MD**

* Maternite Les Bluets 75011 Paris; ** Biochemie pediatrique, Hospital Debrousse 69322 Lyon Cedex 05

A 35-year-old patient G6 P5 with an "unremarkable" medical history attended at her 23 weeks of pregnancy for a routine scan. In her second visit for an amniocetesis (after discussion) the patient declared that she had had the same procedure 9 years before because of a pregnancy with the same characteristcs. The karyotype result was normal (46, XY).

Figure 1: Normal nasal bones

Figure 2: Normal four-chamber view

Figure 3: Polyhydramnios

Figure 4: Small stomach

Figure 5: No sandal gap.


When asked how she felt after the procedure, the mother declared she accepted the amniocentesis because she already had one 9 years ago because her fetus presented with the same features: polyhydramnios, very small stomach, few movements. She had simply "forgotten" to mention the story, because, she said, the memory of the lost child (IUD at 32 weeks) was still to painful. She had delivered three normal babies thereafter.

After investigation we managed to find her previous file where the fetopathologist: (hepatosplenomegaly) and the biochemist had concluded GAUCHER type II (autosomal recessive)

The probable explanation for the present symptoms was: recurrence of the neuropathic form with swallowing palsy explaining polyhydramnios and empty stomach, and fetal akinesia.

So, part of the amniotic fluid was rerouted to the biochemistry where the diagnosis was confirmed.

Karyotype: 46XY normal

Amniocytes culture:


Beta glucosidase Microkat/kg

- Ac. Taur +Ac. Taur.



Betagmuc + Ac. Taur.


X 100


1,85 0,22





16,15 113,40





Conclusion: Gaucher disease


Synonym(s) Glucocerebrosidase deficiency

Included disease(s) Gaucher disease type 1 Gaucher disease type 2 Gaucher disease type 3

Gaucher disease is due to deficiency in a lysosomal enzyme called beta-glucocerebrosidase. Transmission is autosomal recessive. It is characterized by deposit of glucosylceramide in the cells of the liver, spleen and bone marrow. The acute and chronic neuronopathic forms of the disease (types 2 and 3) account for only 5% of all patients with Gaucher. Thus these forms are less frequent than the non neuronopathic form (type 1). Gaucher disease is usually associated with spleno- and hepatomegaly, fatigue, skeletal complications (Erlenmeyer-flask deformity, osteopenia and osteonecrosis) and several corresponding hematological (thrombopenia, anemia) and laboratory (increase in angiotensin-converting enzyme, ferritin, acid phosphatase tartrate-resistant, chitotriosidase) abnormalities. Symptoms of the central nervous system are also observed, in types 2 and 3 only. Diagnosis is established by an assay for glucocerebrosidase activity in peripheral leukocytes. Treatment consisting in enzyme replacement (imiglucerase: recombinant enzyme preparation) allows improvement of haematological abnormalities, hepato-splenomegaly and life quality within a few months. Regression of skeletal complications is usually seen after 3-4 years only. Recently gene therapy trials have been started successfully. *Authors: * Drs J. Stirnemann, I. Caubel et N. Belmatoug (April 2003)*.


PUBMED: Elstein D, Abrahamov A, Dweck A, Hadas-Halpern I, Zimran A.

Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel. [email protected]

Gaucher disease, the most prevalent lysosomal storage disorder, is inherited as an autosomal recessive condition. The gold standard for diagnosis is decreased acid beta-glucosidase activity in the lymphocytes or fibroblasts; molecular analysis of mutations allows for some prognostication of disease severity. Prenatal diagnosis and carrier testing for at-risk families are currently available. There is tremendous phenotypic heterogeneity in the non-neuronopathic form (type I), ranging from clinically asymptomatic to massive hepatomegaly, hypersplenism, growth retardation in children and extensive involvement of bone and lungs. Presence on one allele of the most common mutation, N370S, which is the most prevalent among Ashkenazi Jews for whom there is a predilection for Gaucher disease, is protective of neurological involvement. Some mutations, such as 84GG and IVS2+1, are associated with more severe disease manifestations when appearing as compound heterozygotes with N370S, but when occurring in the homozygous state are not compatible with life. Other mutations, such as L444P, are associated with severe non-neurological disease when occurring as compound heterozygotes with N370S, but when occurring in the homozygous state may be predictive of neurological disease of either acute (type II) or subacute (type III) forms. In the past decade, enzyme replacement therapy has become available which has resulted in a reduction in liver and spleen volume and consequently improved anemia and thrombocytopenia in most patients. It has also engendered catch-up growth in many children, induced improvement in lung involvement secondary to Gaucher disease, and to some extent ameliorated episodes of bone pain. By virtue of treatment, many children who may have been severely affected no longer need to undergo splenectomy to treat hypersplenism, and therefore they are not at risk of bone involvement consequent to the loss of the preferred reservoir for lipid-laden "Gaucher cells". However, enzyme treatment is ineffective in reversing neurological signs, requires a lifelong commitment to intravenous infusions, thereby reducing quality of life, and is relatively expensive for many national health schemes. Hence, alternative forms of treatment, such as substrate balance, are being explored. Symptomatic management, including orthopedic surgery, pain relief for bone pain and even splenectomy, still has importance for patients with Gaucher disease. In addition, there is the potential for bone marrow transplantation and, in the future, gene therapy to be curative, particularly for patients with the neuronopathic forms.



A number sign (#) is used with this entry because the Gaucher disease type II is caused by mutation in the gene encoding acid beta-glucosidase (GBA; 606463). Mutation in the same gene causes Gaucher disease type I (230800) and type III (231000).

In type II Gaucher disease (also called the infantile cerebral type or acute neuronopathic type), enlargement of the abdomen from hepatosplenomegaly and neurologic signs such as retroflexion of the head, strabismus, dysphagia, choking spells, and hypertonicity are features. Death usually occurs before the age of 1 year. Drukker et al. (1970) described a case in a Sephardic-Jewish infant in Gaucher"s disease. This low-oil magnification view of a bone marrow aspirate shows a giant binucleate storage cell filled with glucocerebrosides which accumulate because of an hereditary deficiency of Beta-glucocerebrosidase. The fibrillar pattern is characteristic.


Reférences :

Mignot C et al. Perinatal-lethal Gaucher dise...[PMID: 12838552]

Elstein D et al. Gaucher disease: pediatric co...[PMID: 12083970]

Lee YS et al. Type II Gaucher disease: comp...[PMID: 11336129]

Fasouliotis SJ et al. Gaucher"s disease and pregnan...[PMID: 9643638]

Tsai FJ et al. Molecular diagnosis of Gauche...[PMID: 8607360]

Suss J. [Acute infantile cerebral for...[PMID: 1773930]


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