Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

type 1 Gaucher disease

1st line – supportive therapy

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type 1 Gaucher disease
1st line – 

supportive therapy

A multidisciplinary approach is essential as these are multisystem disorders; many different consultants may be involved in the care of individual patients. Early involvement of specialist centres is recommended; care should be coordinated by the centre.

The physician should monitor for skeletal disease, haematological malignancies, endocrine and metabolic abnormalities, Parkinson's disease, and liver cirrhosis, and manage these complications as they arise.

Consider – enzyme replacement therapy

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type 1 Gaucher disease
Consider – 

enzyme replacement therapy

Additional treatment recommended for SOME patients in selected patient group

Patients should be treated under consultant supervision. Dose reduction may be possible once patients have been stabilised.

Asymptomatic patients do not warrant treatment.[99] However, enzyme replacement therapy (ERT) should be considered in all symptomatic children, and in adults with significant reductions in blood counts (e.g., haemoglobin level <100 g/L [10 g/dL], platelets <100 x 10⁹/L), significant organ enlargement (e.g., spleen size >10x normal), the presence of skeletal disease demonstrated on magnetic resonance imaging, and/or any other organ damage (e.g., evidence of lung damage).[99][100] ERT is of demonstrated benefit in improving haematological abnormalities, bone pain, reducing liver and spleen size. Bone density, pulmonary function, and quality of life also improve.[106][107][108]

Taliglucerase is a plant-derived form of ERT. In 2012, the Food and Drug Administration in the US approved its use for Gaucher disease, but the European Medicines Agency (EMA)'s Committee for Medicinal Products for Human Use (CHMP) recommended against marketing authorisation.

ERT has been associated with serious hypersensitivity reactions, anaphylaxis, and infusion-related reactions. Consider pre-medication with an antihistamine, antipyretic, and/or corticosteroid.

Primary options

imiglucerase: children and adults: 60 units/kg intravenously every 2 weeks initially, adjust according to response

OR

velaglucerase alfa: children ≥4 years of age and adults: 60 units/kg intravenously every 2 weeks initially, adjust according to response

OR

taliglucerase alfa: children ≥4 years of age and adults: 60 units/kg intravenously every 2 weeks initially, adjust according to response

Consider – substrate reduction therapy

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type 1 Gaucher disease
Consider – 

substrate reduction therapy

Additional treatment recommended for SOME patients in selected patient group

This is suitable for less severely affected patients who are unable to tolerate intravenous therapy or who are allergic to available enzyme replacement therapy preparations.

Substrate reduction therapy has been shown to improve anaemia, thrombocytopenia, liver/spleen enlargement, and osteoporosis.[109][110][111][112][113]

Primary options

miglustat: adults: 100 mg orally three times daily, adjust according to response

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OR

eliglustat: adults: dose depends on CYP2D6 genotype and the co-administration of interacting medications; consult specialist for guidance on dose

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type 2 Gaucher disease

1st line – supportive therapy

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type 2 Gaucher disease
1st line – 

supportive therapy

A multidisciplinary approach is essential as these are multisystem disorders; many different consultants may be involved in the care of individual patients. Early involvement of specialist centres is recommended; care should be coordinated by the centre.

Type 2 Gaucher disease is essentially untreatable. The physician should monitor and treat seizures, neurodevelopmental delay, and eye movement disorders.

Enzyme replacement therapy is not effective.

type 3 Gaucher disease

1st line – supportive therapy

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type 3 Gaucher disease
1st line – 

supportive therapy

A multidisciplinary approach is essential as these are multisystem disorders; many different consultants may be involved in the care of individual patients. Early involvement of specialist centres is recommended; care should be coordinated by the centre.

The physician should monitor and treat complications of eye movement disorders, neurodevelopmental delay, and skeletal disease.

Consider – enzyme replacement therapy

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ONGOING
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type 3 Gaucher disease
Consider – 

enzyme replacement therapy

Additional treatment recommended for SOME patients in selected patient group

Asymptomatic patients do not warrant treatment.[99] However, enzyme replacement therapy (ERT) should be considered in all symptomatic children, and in adults with significant reductions in blood counts (e.g., haemoglobin level <100 g/L [10 g/dL], platelets <100 x 10⁹/L), significant organ enlargement (e.g., spleen size >10x normal), the presence of skeletal disease demonstrated on magnetic resonance imaging, and/or any other organ damage (e.g., evidence of lung damage).[99][100] The visceral and skeletal aspects of the disease respond well to ERT, but neurological manifestations will not be improved as ERT cannot cross the blood-brain barrier.[116]

ERT has been associated with serious hypersensitivity reactions, anaphylaxis, and infusion-related reactions. Consider pre-medication with an antihistamine, antipyretic, and/or corticosteroid.

Primary options

imiglucerase: children and adults: 60 units/kg intravenously every 2 weeks initially, adjust according to response

OR

velaglucerase alfa: children ≥4 years of age and adults: 60 units/kg intravenously every 2 weeks initially, adjust according to response

Fabry disease

1st line – supportive therapy

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ONGOING
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Fabry disease
1st line – 

supportive therapy

A multidisciplinary approach is essential as these are multisystem disorders; many different consultants may be involved in the care of individual patients. Early involvement of specialist centres is recommended; care should be coordinated by the centre.

There are a large number of general supportive aspects in the management of this multisystem disease.

Consider – enzyme replacement or chaperone therapy

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Fabry disease
Consider – 

enzyme replacement or chaperone therapy

Additional treatment recommended for SOME patients in selected patient group

Antibody production is provoked by enzyme replacement therapy (ERT) in males, but the impact of this on the efficacy of treatment is unknown. Females do not develop antibodies, perhaps because they are heterozygous and have circulating enzyme.

ERT can slow the progress of organ damage in kidneys and the heart, but these organs may not be returned to normal function. Males should be treated as soon as they are diagnosed; females should be treated if they have symptoms of major organ involvement.[67] ERT initiation should be considered in asymptomatic female patients with laboratory, histological, or imaging evidence of kidney, heart, or central nervous system involvement.[67]

Agalsidase alfa, and agalsidase beta are both effective at preventing renal and cardiovascular complications, compared with no treatment. Agalsidase beta is associated with a lower risk of cerebrovascular complications, compared with agalsidase beta or no treatment.[134] ERT is effective at reducing pain scores and globotriaosylceramide concentrations in plasma, kidney, and heart.[122]

Recommendations have been published on the use of ERT if there is a shortage of this therapy.[170] These recommendations were published in 2011 when agalsidase beta (one of the two available products for Fabry disease) was undergoing production difficulties.

Pegunigalsidase alfa is another option for treating Fabry disease in adults and has the advantage of a longer plasma half-life.[135]

ERT has been associated with serious hypersensitivity reactions, anaphylaxis, and infusion-related reactions. Consider pre-medication with an antihistamine, antipyretic, and/or corticosteroid.

Migalastat is an oral chaperone that increases the activity of the endogenous alpha-galactosidase A enzyme in patients with an amenable mutation. Trials have demonstrated the safety and utility of this therapy in patients with amenable mutations, and the treatment is now licensed and available in the US, Europe, Canada, Japan, and several other countries.[137][138][139][140] Physicians must confirm that the patient’s mutation is amenable. The manufacturer advises avoidance if the estimated glomerular filtration rate (eGFR) is less than 30 mL/minute/1.73 m². Migalastat is suitable for both naive patients and for patients switching from ERT.[141]

Primary options

agalsidase alfa: children ≥7 years of age and adults: 0.2 mg/kg intravenously every 2 weeks

OR

agalsidase beta: children ≥8 years of age and adults: 1 mg/kg intravenously every 2 weeks

OR

pegunigalsidase alfa: adults: 1 mg/kg intravenously every 2 weeks

OR

migalastat: adults: 123 mg orally once daily on alternate days

Plus – TIA and stroke prophylaxis

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Fabry disease
Plus – 

TIA and stroke prophylaxis

Treatment recommended for ALL patients in selected patient group

Stroke and transient ischaemic attack (TIA) require careful primary and secondary preventive measures.

Plus – pain relief

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Fabry disease
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with neuropathic pain
Plus – 

pain relief

Treatment recommended for ALL patients in selected patient group

Pain relief with gabapentin or pregabalin is indicated for neuropathic pain. Carbamazepine is also widely used.[67][117]

Non-steroidal anti-inflammatory drugs should be used sparingly as these patients often have a nephropathy.

Primary options

gabapentin: children: consult specialist for guidance on dose; adults: 1800-3600 mg/day orally given in 3-4 divided doses

OR

pregabalin: children: consult specialist for guidance on dose; adults: 150-300 mg/day orally given in 3 divided doses

OR

carbamazepine: children: consult specialist for guidance on dose; adults: 200-1600 mg/day orally given in 3-4 divided doses

Plus – cosmetic surgery or laser treatment

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Fabry disease
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with cutaneous lesions
Plus – 

cosmetic surgery or laser treatment

Treatment recommended for ALL patients in selected patient group

Cutaneous lesions may require cosmetic surgery or laser therapy. [Figure caption and citation for the preceding image starts]: Cutaneous lesions in Fabry's disease: (A) flank, (B) genitals, (C) umbilicus, (D) lower back, (E) toesOrteu CH, Jansen T, Lidove O, et al. Fabry disease and the skin: data from FOS, the Fabry Outcome Survey. Br J Dermatol. 2007 Aug;157(2):331-7; used with permission [Citation ends].com.bmj.content.model.Caption@413ae177[Figure caption and citation for the preceding image starts]: Cutaneous lesions in Fabry's disease: (A) palms, (B) lips, (C) labial mucosaOrteu CH, Jansen T, Lidove O, et al. Fabry disease and the skin: data from FOS, the Fabry Outcome Survey. Br J Dermatol. 2007 Aug;157(2):331-7; used with permission [Citation ends].com.bmj.content.model.Caption@7c04989d

Plus – ACE inhibitor or angiotensin-II receptor antagonist

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Fabry disease
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with hypertension or proteinuria
Plus – 

ACE inhibitor or angiotensin-II receptor antagonist

Treatment recommended for ALL patients in selected patient group

Blood pressure and proteinuria should be regularly monitored with early intervention.

Primary options

enalapril: children: consult specialist for guidance on dose; adults: 2.5 to 40 mg orally once daily

OR

irbesartan: children: consult specialist for guidance on dose; adults: 150-300 mg orally once daily

Plus – pacemaker + assessment for cardiac surgery

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Fabry disease
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with arrhythmias
Plus – 

pacemaker + assessment for cardiac surgery

Treatment recommended for ALL patients in selected patient group

Cardiac review is essential in patients with Fabry disease. Early recognition of arrhythmia is important and should be managed with a pacemaker. In addition, surgery, including insertion of pacemakers, septal resection, valve replacement, and even cardiac transplantation should all be considered.[119]

mucopolysaccharidosis (MPS)

1st line – supportive therapy

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mucopolysaccharidosis (MPS)
1st line – 

supportive therapy

A multidisciplinary approach is essential as these are multisystem disorders; many different consultants may be involved in the care of individual patients. Early involvement of specialist centres is recommended; care should be coordinated by the centre.

Musculoskeletal problems include spinal deformity, carpal tunnel syndrome, and compression neuropathy. There may be spinal cord compression due to stenosis at the craniocervical region.[145] Communicating hydrocephalus and seizures can occur. Patients can also have cardiac valvular disease requiring surgical assessment.

All these disorders require detailed assessment. Physiotherapy, braces, local injections are all possible; surgical therapy may be required.[144][145]

Plus – enzyme replacement therapy

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mucopolysaccharidosis (MPS)
Plus – 

enzyme replacement therapy

Treatment recommended for ALL patients in selected patient group

Enzyme replacement therapy (ERT) is of established benefit in MPS I, II, IVA (Morquio A syndrome), VI, and type VII (Sly syndrome).[148][149][150][151][152]​ Various enzymes are approved for these indications. In the UK, the National Institute for Health and Care Excellence recommends elosulfase alfa as an option for treating MPS IVA for people of all ages, and it is only available under a commercial arrangement agreement.[153] Phase 3 trials with vestronidase alfa are ongoing.[154][155]

ERT has been associated with serious hypersensitivity reactions, anaphylaxis, and infusion-related reactions. Consider pre-medication with an antihistamine, antipyretic, and/or corticosteroid.

Primary options

MPS I

laronidase: children ≥5 years of age and adults: 0.58 mg/kg intravenously once weekly

OR

MPS II

idursulfase: children ≥5 years of age and adults: 0.5 mg/kg intravenously once weekly

OR

MPS IVA (Morquio A syndrome)

elosulfase alfa: children ≥5 years of age and adults: 2 mg/kg intravenously once weekly

OR

MPS VI

galsulfase: children ≥5 years of age and adults: 1 mg/kg intravenously once weekly

OR

MPS VII

vestronidase alfa: children and adults: 4 mg/kg intravenously every 2 weeks

Consider – stem cell transplant

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mucopolysaccharidosis (MPS)
Consider – 

stem cell transplant

Additional treatment recommended for SOME patients in selected patient group

Stem cell transplantation should be considered for severely affected patients and is of established value in, for example, severe MPS I and MPS VI.[147]

Pompe disease

1st line – supportive therapy

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Pompe disease
1st line – 

supportive therapy

A multidisciplinary approach is essential as these are multisystem disorders; many different consultants may be involved in the care of individual patients. Early involvement of specialist centres is recommended; care should be coordinated by the centre.

General and supportive care for neonates is multidisciplinary, involving neurologists, anaesthetists, and cardiologists.

Respiratory failure and obstructive sleep apnoea may require different degrees of ventilatory support.

Consider – enzyme replacement therapy

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ONGOING
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Pompe disease
Consider – 

enzyme replacement therapy

Additional treatment recommended for SOME patients in selected patient group

Enzyme replacement therapy (ERT) for children and adults is licensed. Avalglucosidase is an option for late-onset Pompe disease in children 1 year of age and older.

Cipaglucosidase alfa is another option which is approved for the treatment of late-onset Pompe disease in adults who are not improving on their current ERT. Cipaglucosidase alfa is only approved for use in combination with miglustat (an enzyme stabiliser).[165]

European consensus guidelines recommend an initial 2-year period of ERT for symptomatic adults. ERT may be continued during pregnancy and lactation. Skeletal muscle and respiratory function should be assessed during treatment.[166]

ERT has been associated with serious hypersensitivity reactions, anaphylaxis, and infusion-related reactions. Consider pre-medication with an antihistamine, antipyretic, and/or corticosteroid.

Primary options

alglucosidase alfa: children and adults: 20 mg/kg intravenously every 2 weeks

OR

avalglucosidase alfa: children ≥1 year of age and <30 kg: 40 mg/kg intravenously every 2 weeks; children ≥1 year of age and ≥30 kg and adults: 20 mg/kg intravenously every 2 weeks

OR

cipaglucosidase alfa: adults ≥40 kg body weight: 20 mg/kg intravenously every 2 weeks

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and

miglustat: adults ≥40 kg to <50 kg body weight: 195 mg orally every 2 weeks; adults ≥50 kg body weight: 260 mg orally every 2 weeks

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Tay-Sachs disease

1st line – supportive therapy

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Tay-Sachs disease
1st line – 

supportive therapy

Palliative care only is required for the infantile form.

Juvenile-onset and chronic or adult-onset forms require supportive care, special needs education, and neurological assessment. Dementia and ataxia are long-term complications that warrant consideration in management.

Enzyme replacement therapy is not available for Tay-Sachs disease.

Niemann-Pick disease

1st line – supportive therapy

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Niemann-Pick disease
1st line – 

supportive therapy

Palliative care only is required for the severe infantile form of Niemann-Pick type A. Supportive care is indicated for less severe forms.

Niemann-Pick type B typically presents in adults with pulmonary disease and/or hepatosplenomegaly.

Niemann-Pick type C is extremely variable, but neurological assessment is usually important. Enzyme replacement therapy is available for type C.

Consider – substrate reduction therapy

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ONGOING
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Niemann-Pick disease
Consider – 

substrate reduction therapy

Additional treatment recommended for SOME patients in selected patient group

Substrate reduction therapy (SRT) is only available for Niemann-Pick type C.[54] SRT with miglustat has been shown to stabilise neurodegenerative symptoms, including dysphagia.[168]

Primary options

miglustat: adults: 100 mg orally three times daily, adjust according to response

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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