Common hereditary lysosomal storage diseases

Last reviewed: 30 May 2022
Last updated: 15 Jun 2022

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
More key diagnostic factors

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
Other diagnostic factors

Risk factors

  • male sex (mucopolysaccharidosis [MPS] II, Fabry disease)
  • Ashkenazi ethnicity
More risk factors

Diagnostic investigations

1st investigations to order

  • enzyme assay
  • substrate assay
  • DNA analysis
  • CBC
More 1st investigations to order

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)
More investigations to consider

Treatment algorithm

ONGOING

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.

  • Common hereditary lysosomal storage diseases images
  • 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 Differentials
  • Guidelines

    • 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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