Last reviewed: 20 Dec 2021
Last updated: 26 Oct 2021



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



Atul B. Mehta, MA, MB BChir, MD, FRCP, FRCPath

Consultant Haematologist

Royal Free Hospital

Professor in Haematology

University College London




ABM has received research funding, travel grants for educational meetings, and consultancy fees from Sanofi Genzyme, Takeda, Lilly, Actelion, Biomarin, Protalix, Pfizer, Freeline, and Amicus. 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



GMP declares that he has no competing interests.

Uma Ramaswami, MD, FRCPCH

Consultant Paediatrician

Paediatric Metabolic Unit

Cambridge University Hospitals




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




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




EVV declares that he has no competing interests.

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