0
March 3, 1993, Vol 269, No. 9 >
ARTICLE | March 3, 1993

Clinical Heterogeneity Among Patients With Gaucher's Disease FREE

Ellen Sidransky, MD; Edward I. Ginns, MD, PhD
[+] Author Affiliations

Reprint requests to Unit on Clinical Genetics, Section on Molecular Neurogenetics, Clinical Neuroscience Branch, National Institute of Mental Health, Bldg 10, Room 3N256, 9000 Rockville Pike, Bethesda, MD 20892 (Dr Sidransky).


JAMA. 1993;269(9):1154-1157. doi:10.1001/jama.1993.03500090090038
Text Size: A A A
Published online
Article
References

SELECTED CASES 

Case 1  A girl born at term to nonconsanguineous parents by spontaneous vaginal delivery had normal early developmental milestones. She smiled at 9 weeks, cooed at 10½ weeks, and rolled over at 14 weeks. However, she developed constant irritability and, on examination, was noted to have hepatosplenomegaly. A liver biopsy performed at 7 months of age revealed Gaucher's disease. Her clinical course was characterized by progressive spasticity, respiratory difficulties, and feeding problems. Treatment of seizures and apnea required frequent hospitalizations; however, she died of apnea at 11 months of age.

Comment.  —This child demonstrates the clinical course that is typically associated with type 2 (acute neurologic) Gaucher's disease.1 Usually, these children are clinically normal at birth and achieve early developmental milestones, but during the first year of life, degenerative neurological disease becomes apparent. The classic clinical triad that rapidly develops includes strabismus, trismus, and hyperextension of the

REFERENCES

1 +
Barranger JA, Ginns EI.  Glucosylceramide lipidoses: Gaucher disease.  In: Scriver CR, Beaud AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease . 6th ed. New York, NY: McGraw-Hill International Book Co; 1989;:1677-1698.
2 +
Martin BM, Sidransky E, Ginns El.  Gaucher disease: advances and challenges. Adv Pediatr . 1989;; 36:277-306.
3 +
Tybulewicz V, Tremblay ML, LaMarca ME, et al.  Targeted disruption of the mouse glucocerebrosidase gene: development of an animal model of Gaucher disease. Nature . 1992;;357:407-410.
4 +
Sidransky E, Sherer D, Ginns El.  Gaucher disease in the neonate: a distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene. Pediatr Res . 1992;;32:494-498.
5 +
Liu K, Commens C, Choong R, Jaworski R.  Collodion babies with Gaucher's disease. Arch Dis Child . 1988;;63:854-856.
6 +
Lipson AH, Rogers M, Berry A.  Collodion babies with Gaucher's disease: a further case. Arch Dis Child . 1991;;66:667.
7 +
Girgensohn H, Kellner H, Südhof H.  Angeborener morbus Gaucher bei erythroblastose und Gefässverkalkung. Klin Wochenschr . 1954;;32:57-64.
8 +
Sun CC, Panny S, Combs J, Gutberlett R.  Hydrops fetalis associated with Gaucher disease. Pathol Res Pract . 1984;;179:101-104.
9 +
Frederickson DS, Sloan HR.  Glucosyl ceramide lipidoses: Gaucher's disease.  In: Stanbury JB, Wyngaarden JB, Frederickson DS, eds. The Metabolic Basis of Inherited Disease . New York, NY: McGraw-Hill International Book Co; 1972;: 730-759.
10 +
Sidransky E, Tsuji S, Stubblefield BK, et al.  Gaucher patients with oculomotor abnormalities do not have a unique genotype. Clin Genet . 1992;;41: 1-5.
11 +
Cogan DG, Chu FC, Reingold D, Barranger J.  Ocular motor signs in some metabolic diseases. Arch Ophthalmol . 1981;;99:1802-1808.
12 +
Erikson A.  Gaucher disease: Norrbottnian type III. Acta Pediatr Scand Suppl . 1988;;326:1-41.
13 +
Berrebi A, Wishnitzer R, Von-der-Walde V.  Gaucher's disease: unexpected diagnosis in three patients over seventy years old. Nouv Rev Fr Hematol . 1984;;26:201-203.
14 +
Zimran A, Gelbart T, Westwood B, Grabowski GA, Beutler E.  High frequency of the 1226 mutation for type I Gaucher disease among the Ashkenazi Jewish population. Am J Hum Genet . 1991;; 49:855-859.
15 +
Matoth Y, Chazan S, Cnaan A, et al.  Frequency of carriers of chronic (type 1) Gaucher disease in Ashkenazi Jews. Am J Med Genet . 1987;;27:561-565.
16 +
Gaucher P. De l'epithelioma primitif de la rate. Thése de Paris. 1882.
17 +
Ginns EI, Choudary PV, Tsuji S, et al.  Gene mapping and leader polypeptide sequence of human glucocerebrosidase: implications for Gaucher disease. Proc Natl Acad Sci US A . 1985;;82:7101-7105.
18 +
Horowitz M, Wilder S, Horowitz Z, Reiner O, Gelbart T, Beutler E.  The human glucocerebrosidase gene and pseudogene: structure and evolution. Genomics . 1989;;4:87-96.
19 +
Tsuji S, Choudary PV, Martin BM, et al.  A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher disease. N Engl J Med . 1987;;316:570-575.
20 +
Tsuji S, Martin BM, Barranger JA, et al.  Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals. Proc Natl Acad Sci U S A . 1988;;85: 2349-2352.
21 +
Hong CM, Ohashi T, Yu XJ, Weiler S, Barranger JA.  Sequence of two alleles responsible for Gaucher disease. DNA Cell Biol . 1990;;9:233-241.
22 +
Beutler E.  New molecular approaches to diagnosis and treatment. Science . 1992;;256:794-799.
23 +
Latham TE, Theophilus BDM, Grabowski GA, Smith FI.  Heterogeneity of mutations in the acid β-glucosidase gene of Gaucher disease patients. DNA Cell Biol . 1991;;10:15-21.
24 +
Eyal N, Wilder S, Horowitz M.  Prevalent and rare mutations among Gaucher patients. Gene . 1990;; 96:277-283.
25 +
Sidransky E, Tsuji S, Martin BM, Stubblefield B, Ginns EI.  DNA mutation analysis of Gaucher patients. Am J Med Genet . 1992;;42:331-336.
26 +
Beutler E, Gelbart T, Kuhl W, Sorge J, West C.  Identification of the second common Jewish Gaucher disease mutation makes possible population based screening for the heterozygote state. Proc Natl Acad Sci U S A . 1991;;88:10544-10547.
27 +
Wenger DA, Roth S, Sattler M.  Acute neuronopathic (infantile) and chronic nonneuronopathic (adult) Gaucher disease in full siblings. J Pediatr . 1982;;100:252-257.
28 +
Herrlim KM, Hillborg PO.  Neurological signs in a juvenile form of Gaucher's disease. Acta Pediatr Scand . 1962;;51:137-154.
29 +
Nishimura RN, Barranger JA.  Neurologic complications of Gaucher's disease type 3. Arch Neurol . 1980;;37:92-93.
30 +
Dahl N, Lagerström, Erickson A, Petterson V.  Gaucher disease type III (Norrbottnian type) is caused by a single mutation in exon 10 of the glucocerebrosidase gene. Am J Hum Genet . 1990;;47: 275-278.
31 +
Rappeport JM, Ginns EI.  Bone-marrow transplantation in severe Gaucher's disease. N Engl J Med . 1984;;311:84-88.
32 +
Whittington R, Goa KL.  Alglucerase: a review of its therapeutic use in Gaucher's disease. Drugs . 1992;;44:72-93.
33 +
Martin B, Galdzicka M, Eliason E, et al.  Development of polyethylene glycol modified recombinant human glucocerebrosidase for enzyme 15 replacement therapy in Gaucher disease. Am J Hum Genet . 1992;;51:307.
34 +
Choudary PV, Tsuji S, Martin BM, et al.  The molecular biology of Gaucher disease and the potential for gene therapy. Cold Spring Harb Symp Quant Biol . 1986;;51:1047-1051.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Barranger JA, Ginns EI.  Glucosylceramide lipidoses: Gaucher disease.  In: Scriver CR, Beaud AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease . 6th ed. New York, NY: McGraw-Hill International Book Co; 1989;:1677-1698.
2 +
Martin BM, Sidransky E, Ginns El.  Gaucher disease: advances and challenges. Adv Pediatr . 1989;; 36:277-306.
3 +
Tybulewicz V, Tremblay ML, LaMarca ME, et al.  Targeted disruption of the mouse glucocerebrosidase gene: development of an animal model of Gaucher disease. Nature . 1992;;357:407-410.
4 +
Sidransky E, Sherer D, Ginns El.  Gaucher disease in the neonate: a distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene. Pediatr Res . 1992;;32:494-498.
5 +
Liu K, Commens C, Choong R, Jaworski R.  Collodion babies with Gaucher's disease. Arch Dis Child . 1988;;63:854-856.
6 +
Lipson AH, Rogers M, Berry A.  Collodion babies with Gaucher's disease: a further case. Arch Dis Child . 1991;;66:667.
7 +
Girgensohn H, Kellner H, Südhof H.  Angeborener morbus Gaucher bei erythroblastose und Gefässverkalkung. Klin Wochenschr . 1954;;32:57-64.
8 +
Sun CC, Panny S, Combs J, Gutberlett R.  Hydrops fetalis associated with Gaucher disease. Pathol Res Pract . 1984;;179:101-104.
9 +
Frederickson DS, Sloan HR.  Glucosyl ceramide lipidoses: Gaucher's disease.  In: Stanbury JB, Wyngaarden JB, Frederickson DS, eds. The Metabolic Basis of Inherited Disease . New York, NY: McGraw-Hill International Book Co; 1972;: 730-759.
10 +
Sidransky E, Tsuji S, Stubblefield BK, et al.  Gaucher patients with oculomotor abnormalities do not have a unique genotype. Clin Genet . 1992;;41: 1-5.
11 +
Cogan DG, Chu FC, Reingold D, Barranger J.  Ocular motor signs in some metabolic diseases. Arch Ophthalmol . 1981;;99:1802-1808.
12 +
Erikson A.  Gaucher disease: Norrbottnian type III. Acta Pediatr Scand Suppl . 1988;;326:1-41.
13 +
Berrebi A, Wishnitzer R, Von-der-Walde V.  Gaucher's disease: unexpected diagnosis in three patients over seventy years old. Nouv Rev Fr Hematol . 1984;;26:201-203.
14 +
Zimran A, Gelbart T, Westwood B, Grabowski GA, Beutler E.  High frequency of the 1226 mutation for type I Gaucher disease among the Ashkenazi Jewish population. Am J Hum Genet . 1991;; 49:855-859.
15 +
Matoth Y, Chazan S, Cnaan A, et al.  Frequency of carriers of chronic (type 1) Gaucher disease in Ashkenazi Jews. Am J Med Genet . 1987;;27:561-565.
16 +
Gaucher P. De l'epithelioma primitif de la rate. Thése de Paris. 1882.
17 +
Ginns EI, Choudary PV, Tsuji S, et al.  Gene mapping and leader polypeptide sequence of human glucocerebrosidase: implications for Gaucher disease. Proc Natl Acad Sci US A . 1985;;82:7101-7105.
18 +
Horowitz M, Wilder S, Horowitz Z, Reiner O, Gelbart T, Beutler E.  The human glucocerebrosidase gene and pseudogene: structure and evolution. Genomics . 1989;;4:87-96.
19 +
Tsuji S, Choudary PV, Martin BM, et al.  A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher disease. N Engl J Med . 1987;;316:570-575.
20 +
Tsuji S, Martin BM, Barranger JA, et al.  Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals. Proc Natl Acad Sci U S A . 1988;;85: 2349-2352.
21 +
Hong CM, Ohashi T, Yu XJ, Weiler S, Barranger JA.  Sequence of two alleles responsible for Gaucher disease. DNA Cell Biol . 1990;;9:233-241.
22 +
Beutler E.  New molecular approaches to diagnosis and treatment. Science . 1992;;256:794-799.
23 +
Latham TE, Theophilus BDM, Grabowski GA, Smith FI.  Heterogeneity of mutations in the acid β-glucosidase gene of Gaucher disease patients. DNA Cell Biol . 1991;;10:15-21.
24 +
Eyal N, Wilder S, Horowitz M.  Prevalent and rare mutations among Gaucher patients. Gene . 1990;; 96:277-283.
25 +
Sidransky E, Tsuji S, Martin BM, Stubblefield B, Ginns EI.  DNA mutation analysis of Gaucher patients. Am J Med Genet . 1992;;42:331-336.
26 +
Beutler E, Gelbart T, Kuhl W, Sorge J, West C.  Identification of the second common Jewish Gaucher disease mutation makes possible population based screening for the heterozygote state. Proc Natl Acad Sci U S A . 1991;;88:10544-10547.
27 +
Wenger DA, Roth S, Sattler M.  Acute neuronopathic (infantile) and chronic nonneuronopathic (adult) Gaucher disease in full siblings. J Pediatr . 1982;;100:252-257.
28 +
Herrlim KM, Hillborg PO.  Neurological signs in a juvenile form of Gaucher's disease. Acta Pediatr Scand . 1962;;51:137-154.
29 +
Nishimura RN, Barranger JA.  Neurologic complications of Gaucher's disease type 3. Arch Neurol . 1980;;37:92-93.
30 +
Dahl N, Lagerström, Erickson A, Petterson V.  Gaucher disease type III (Norrbottnian type) is caused by a single mutation in exon 10 of the glucocerebrosidase gene. Am J Hum Genet . 1990;;47: 275-278.
31 +
Rappeport JM, Ginns EI.  Bone-marrow transplantation in severe Gaucher's disease. N Engl J Med . 1984;;311:84-88.
32 +
Whittington R, Goa KL.  Alglucerase: a review of its therapeutic use in Gaucher's disease. Drugs . 1992;;44:72-93.
33 +
Martin B, Galdzicka M, Eliason E, et al.  Development of polyethylene glycol modified recombinant human glucocerebrosidase for enzyme 15 replacement therapy in Gaucher disease. Am J Hum Genet . 1992;;51:307.
34 +
Choudary PV, Tsuji S, Martin BM, et al.  The molecular biology of Gaucher disease and the potential for gene therapy. Cold Spring Harb Symp Quant Biol . 1986;;51:1047-1051.

Letters

Submit a Letter
CME Course for:


You need to register in order to view this quiz.


To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Response

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2012 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems