Summary
Definition
History and exam
Key diagnostic factors
- Family history
- onset in childhood (MPS, Pompe, Gaucher, Fabry, Niemann-Pick type A)
- onset in adolescence (Fabry, Pompe, Gaucher types 1, 3, mucopolysaccharidosis, Niemann-Pick types B, C)
- onset in adulthood (Fabry, Gaucher type 1, Pompe)
- hepatomegaly and/or splenomegaly
- hyperacusis
- history of renal failure
- skin rash/cutaneous lesions
- large head circumference
- macular "cherry red spot" on ophthalmoscopy
- optic atrophy or retinitis pigmentosa on ophthalmoscopy
- corneal clouding on ophthalmoscopy
- fatigue
Other diagnostic factors
- neurodevelopmental delay
- hearing impairment/sudden deafness
- cataract on ophthalmoscopy
- eye movement disorder
- progressive dementia and ataxia or gait disturbance
- failure to thrive
- joint contracture
- depression
- skeletal abnormalities including spinal gibbus
- hydrocephalus
- history of recurrent respiratory tract infections
- psychosis
- movement disorders
- premature stroke/transient ischemic attack
- cardiomegaly
- valvular cardiac disease
Risk factors
- male sex (mucopolysaccharidosis [MPS] II, Fabry disease)
- Ashkenazi ethnicity
Diagnostic investigations
1st investigations to order
- enzyme assay
- substrate assay
- DNA analysis
- CBC
Investigations to consider
- ECG
- echocardiogram
- pulmonary function tests
- bone marrow biopsy
- muscle biopsy
- CT/MRI of enlarged organ (Gaucher)
- echocardiogram/ultrasound/MRI (Fabry)
- CT/x-ray (mucopolysaccharidosis)
Treatment algorithm
type 1 Gaucher disease
type 2 Gaucher disease
type 3 Gaucher disease
Fabry disease
mucopolysaccharidosis (MPS)
Pompe disease
Tay-Sachs disease
Niemann-Pick disease
Contributors
Authors
Atul B. Mehta, MA, MB BChir, MD, FRCP, FRCPath
Consultant Haematologist
Royal Free Hospital
Professor in Haematology
University College London
London
UK
Disclosures
ABM has served on advisory boards, received travel grants, research grants, undertaken clinical trials in association with and provided support for educational activities for Takeda, Sanofi-Genzyme, Amicus, Biomarin, Pfizer/Protalix, Freeline therapeutics, Prevail/Lilly, and AvroBio. He is also an author of a number of references cited in this topic.
Peer reviewers
Gregory M. Pastores, MD
Associate Professor
Departments of Neurology and Pediatrics
NYU School of Medicine
New York
NY
Disclosures
GMP declares that he has no competing interests.
Uma Ramaswami, MD, FRCPCH
Consultant Paediatrician
Paediatric Metabolic Unit
Cambridge University Hospitals
Cambridge
UK
Disclosures
UR has received travel grants, honoraria for lectures, and funding for clinical trials from Shire HGT, Genzyme, and Actelion.
Michael Beck, MD
Head of Department
Children's Hospital
University of Mainz
Mainz
Germany
Disclosures
MB has been reimbursed by Shire, the manufacturer of Elaprase and Replagal, for attending several conferences, for running educational programs and for consulting. MB has received honoraria for speaking from Genzyme (the manufacturer of Myozyme, Fabrazyme, Aldurazyme, and Cerezyme) and Actelion (the manufacturer of Zavesca). MB is an author of a number of references cited in this topic.
Elmer V. Villanueva, MD, ScM, FRIPH
Associate Professor of Public Health
Director of Research
Gippsland Medical School
Monash University
Churchill
Australia
Disclosures
EVV declares that he has no competing interests.
Differentials
- Langerhans cell histiocytosis (differential diagnosis of type 2 and 3 Gaucher disease)
- Rheumatic fever (differential diagnosis of Fabry)
- Bacterial endocarditis (differential diagnosis of Fabry)
More DifferentialsGuidelines
- Elosulfase alfa for treating mucopolysaccharidosis type 4A
- Treatment of mucopolysaccharidosis type II (Hunter syndrome): a Delphi derived practice resource of the American College of Medical Genetics and Genomics (ACMG)
More Guidelines
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