| Identifier |
918-1 |
| Title |
Gaucher's Disease |
| Creator |
Shirley H. Wray, MD, PhD, FRCP |
| Contributors |
Steve Smith, Videographer |
| Affiliation |
(SHW) Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital, Boston, Massachusetts |
| Subject |
"Disorder of Horizontal Saccades; Impaired Initiation; Slow Velocity; Arcuate Trajectory; Absent Optokinetic Nystagmus; Normal Vertical Gaze; Normal Pursuit; Juvenile Neuronopathic Gaucher's Disease, Type 3; Autosomal Recessive Linked to Chromosome 1q21; Glucocerebroside Deficiency; Horizontal Gaze Palsy" |
| History |
This little boy has Gaucher's disease. Gaucher's disease is an autosomal recessive disorder, linked to chromosome 1q21, due to glucocerebroside β-glucosidase deficiency. There are three phenotypic variances of Gaucher's disease. Type I is the most common and lacks neurological features. Type 2 is the infantile neuronopathic form, which is characterized by trismus, strabismus, ocular motor apraxia, opisthotonus and death by about two years. Type 3 is a juvenile neuronopathic form with a milder course. The presenting ocular features include: 1. Ocular motor apraxia involving both horizontal and vertical gaze. 2. Slow initiation of horizontal saccades 3. Supranuclear horizontal gaze palsy 4. Normal velocity saccades that appear to stall in mid-flight 5. Slow initiation of saccades with slow velocity and abnormal trajectory i.e. arcuate as in this case. Clinical manifestations include: • Incidental discovery of painless splenomegaly • Thrombocytopenia • Anemia • Leucopenia secondary to hypersplenism and bone pain Moderate hepatic dysfunction is common and rarely, severe hepatic failure, portal hypertension, pulmonary infiltrates and pulmonary hypertension develop. Serum acid phosphatase is characteristically elevated The course is variable, ranging from confinement to wheelchair early in life to asymptomatic diagnosis in the ninth decade. Most patients have a mild course and a relatively normal life expectancy. A partial or total splenectomy may be required. Bone disease: The extent of bone disease is variable and includes bone pain, pathological fractures, as in this little boy, vertebral collapse and aseptic necrosis of the femoral head. Bone pain with fever is termed pseudoosteomyelitis. Gaucher Cell: A distinctive storage cell is present in the bone marrow in all forms of Gaucher's disease, but enzyme assay should be performed because the Gaucher cell also maybe found in patients with granulocytic leukemia and myeloma. Diagnosis: The diagnosis of Gaucher's disease is established by enzyme analysis, and genetic studies. |
| Pathology |
Genetics: Four mutations account for 96 percent of the mutations in Gaucher's disease affecting the Ashkenazic population. These findings opened the way for gentotype/phenotype correlations and carrier screening. One mutation, designated N370S (substitution of serine (S) for asparagine (N) at position 370), is mild; a single copy of this mutation in a compound heterozygote does not cause neurologic involvement, and homozygosity for this mutation is associated with a particularly mild phenotype. In fact, homozygosity for the N370S phenotype was found in 2 of 453 ‘normal' Ashkenazic individuals. |
| Disease/Diagnosis |
Gaucher's Disease |
| Clinical |
This child with Gaucher's disease type 3 has a striking disorder of horizontal saccades. The video shows: Impaired initiation Slow velocity Arcuate trajectory Absent optokinetic nystagmus Normal Vertical Gaze Normal Pursuit |
| Presenting Symptom |
Slow eye movements |
| Ocular Movements |
Disorder of Horizontal Saccades; 1. Impaired initiation; 2. Slow velocity; 3. Arcuate trajectory; 4. Absent optokinetic nystagmus; Normal Vertical Gaze; Normal Pursuit |
| Neuroimaging |
MRI is particularly effective in defining the bony abnormalities |
| Treatment |
A major change in the treatment for Gaucher disease is the availability of enzyme replacement therapy (ERT) with macrophage-targeted β-glucosidase (prepared from human placenta) in patients with type 3 Gaucher's disease. Treatment improves anemia and thrombocytopenia, decreases organomegaly, and decreases bone pain. Supranuclear gaze palsy usually remains stable and only one patient improved. ERT is undergoing clinical trials; however, cost (about $300,000 per year) is likely to remain a major obstacle, and the dosage and indications for treatment are subject of current investigation. |
| Etiology |
Genetic disorder |
| Date |
1990 |
| References |
1. Accardo AP, Pensiero S. Perissutti P. Saccadic analysis for early identification of neurological involvement in Gaucher disease. Ann N Y Acad Sci 2005;1039:503-507. http://www.ncbi.nlm.nih.gov/pubmed/15827009 2. Altarescu G, Hill S, Wiggs E Jeffries N, Kreps C, Parker CC, Brady RO, Barton NW, Schiffmann R. and collaborators. The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease. J Pediatr 2001, 138:539-547. http://www.ncbi.nlm.nih.gov/pubmed/11295718 3. Beutler E. Gaucher's disease. N Engl J Med. 1991;325:1354. http://www.ncbi.nlm.nih.gov/pubmed/1922238 4. Beutler E. Gaucher disease: New molecular approaches to diagnosis and treatment. Science 1992;256:794. http://www.ncbi.nlm.nih.gov/pubmed/1589760 5. Bohlega S, Kambouris M, Shahid M, Al Homsi M, Al Sous W. Gaucher disease with oculomotor apraxia and cardiovascular calcification (Gaucher type IIIC). Neurology 2000;54:261-263. http://www.ncbi.nlm.nih.gov/pubmed/10636167 6. Erikson A, Wahlberg I. Gaucher disease - Norrbottnian type. Ocular abnormalities. Acta Ophthalmol Copenh 1985;63:221-225. http://www.ncbi.nlm.nih.gov/pubmed/4003050 7. Gross-Tsur V, Har-Even Y, Gutman I, Amir N. Oculomotor apraxia: the presenting sign of Gaucher disease. Pediatr Neurol 1989;5:128-129. http://www.ncbi.nlm.nih.gov/pubmed/2712947 8. Harris CM, Taylor DS, VellodiA. Ocular motor abnormalities in Gaucher disease. Neuropediatrics 1999;30:289-293. http://www.ncbi.nlm.nih.gov/pubmed/10706022 9. Leigh JR. Zee DS. Diagnosis and Central Disorders of Ocular Motility. Ch 12, 598-718. In: The Neurology of Eye Movements. 4th Edition. Oxford University Press, New York, 2006. 10. Patterson MC, Horowitz M, Abel R, Currie J, Yu KT, Kaneski C, Higgins J, O'Neill R, Fedio P, Pikus A, Brady R, Barton N. Isolated horizontal supranuclear gaze palsy as a marker of severe systemic involvement in Gaucher's disease. Neurology 1993;43:1993-1997. http://www.ncbi.nlm.nih.gov/pubmed/8413956 11. Vivian AJ. Harris CM, Kriss A. Batin MM, Neville BGR, Taylor DSI. Oculomotor signs in infantile Gaucher disease. Neuro-ophthalmology 1993;13:151-155. 12. Winkelman MD, Banker BQ, Victor M, Moser HW. Non-infantile neuronopathic Gaucher's disease: a clinicopathologic study. Neurology 1983;33:992-1008. http://www.ncbi.nlm.nih.gov/pubmed/6683823 |
| Language |
eng |
| Format |
video/mp4 |
| Type |
Image/MovingImage |
| Source |
3/4" Umatic master videotape |
| Relation is Part of |
162-7, 923-5 |
| Collection |
Neuro-Ophthalmology Virtual Education Library: Shirley H. Wray Collection: https://novel.utah.edu/Wray/ |
| Publisher |
North American Neuro-Ophthalmology Society |
| Holding Institution |
Spencer S. Eccles Health Sciences Library, University of Utah |
| Rights Management |
Copyright 2002. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright |
| ARK |
ark:/87278/s69s4nk7 |
| Setname |
ehsl_novel_shw |
| ID |
188605 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s69s4nk7 |
