AKT · Endocrine/Lipids, metabolic & inheritedlow yield

Lysosomal storage disorders

Inherited lysosomal enzyme deficiencies → substrate accumulation (Gaucher, Niemann-Pick, Fabry, Tay-Sachs)

Overview

A group of inherited (mostly autosomal-recessive; Fabry is X-linked) lysosomal enzyme deficiencies causing accumulation of un-degraded substrate. Examples: Gaucher (glucocerebrosidase — hepatosplenomegaly, bone crises, cytopenias), Niemann-Pick (sphingomyelinase — hepatosplenomegaly, cherry-red macular spot, neurodegeneration), Fabry (α-galactosidase — neuropathic pain, angiokeratomas, renal/cardiac), Tay-Sachs (hexosaminidase A — neurodegeneration, cherry-red spot, no hepatosplenomegaly). Some treated with enzyme replacement.

Recognise

Gaucher: hepatosplenomegaly, bone pain/crises, thrombocytopenia/anaemia (commonest; treatable with enzyme replacement)
Niemann-Pick & Tay-Sachs: neurodegeneration + CHERRY-RED macular spot (Tay-Sachs = no hepatosplenomegaly; Niemann-Pick = hepatosplenomegaly)
Fabry (X-linked): childhood neuropathic limb pain, angiokeratomas, hypohidrosis, progressive renal failure, cardiomyopathy, early stroke

Red flags

Progressive neurodegeneration (Tay-Sachs/Niemann-Pick) — supportive; Fabry → renal/cardiac/stroke surveillance

Differentials & how to tell them apart

Other causes of hepatosplenomegaly/neurodegenerationleukaemia/lymphoma, other inborn errors — enzyme assays discriminate

Mucopolysaccharidoses (Hurler/Hunter)coarse features, organomegaly, skeletal dysplasia — different enzymes

Investigations

Specific enzyme assays and genetics; tissue/bone-marrow findings (Gaucher cells); ophthalmology (cherry-red spot); organ assessment.

Management

Enzyme replacement where available (Gaucher/Fabry); supportive care + genetic counselling

1Recognise the pattern (organomegaly ± neurodegeneration ± cherry-red spot ± angiokeratomas), confirm with enzyme assay/genetics, refer to a metabolic centre.Gate: Identify the TREATABLE ones (Gaucher and Fabry have enzyme replacement) and screen Fabry for the renal/cardiac/stroke complications; cherry-red spot WITHOUT hepatosplenomegaly = Tay-Sachs, WITH = Niemann-Pick
2Enzyme replacement (Gaucher/Fabry); supportive/genetic care for neurodegenerative forms; family counselling and carrier testing.

Enzyme replacement therapy — Gaucher (imiglucerase) and Fabry (agalsidase) — disease-modifying where available

Substrate reduction / supportive care — supportive for neurodegenerative forms (Tay-Sachs)

Key points

Pattern-recognition: Gaucher (hepatosplenomegaly + bone crises, treatable), cherry-red spot (Tay-Sachs none-organomegaly vs Niemann-Pick organomegaly), Fabry (X-linked neuropathic pain + angiokeratomas + renal/cardiac). Enzyme assays confirm.

Monitor & prognosis

Organ function; treatment response.

Variable; enzyme replacement helps Gaucher/Fabry.

Source: BIMDG; StatPearls