| Niemann–Pick disease | | | | |
| Type A | Acid sphingomyelinase deficiency | SMPD1 | Onset in infancy, retinopathy hepatosplenomegaly and rapidly progressive neurological deterioration | Recurrent bronchitis or aspiration pneumonia culminating in life-threatening or fatal events |
| Type B | Acid sphingomyelinase deficiency | SMPD1 | Onset in childhood, hepatosplenomegaly, growth retardation and mild clinical course | Mild dyspnoea on exertion, interstitial lung disease, and severe and fatal respiratory insufficiency |
| Type C | Abnormal trafficking of sphingolipids | NPC1 and NPC2 | Variable age at onset, hepatosplenomegaly, progressive neurological involvement and subacute clinical course | Interstitial lung disease, aspiration pneumonia, and pulmonary alveolar proteinosis with respiratory insufficiency (in NPC2 genotype) |
| Gaucher disease | | | | |
| Type 1 | β-glucocerebrosidase deficiency | GBA (high prevalence of the N370S mutation) | Non-neuronopathic form, hepatosplenomegaly, thrombocytopenia, and bone disease | Ventilatory dysfunction, recurrent respiratory infections and pulmonary hypertension |
| Type 2 | β-glucocerebrosidase deficiency | GBA (high prevalence of L444P/L444P and other “neuronopathic” mutations) | Acute neurological form, early onset, rapidly progressing brainstem dysfunction and hepatosplenomegaly | Ventilatory dysfunction, aspiration pneumonia, and increased risk of interstitial lung disease in homozygotes for L444P mutation |
| Type 3 | β-glucocerebrosidase deficiency | GBA (high prevalence of L444P/L444P mutation) | Subacute progressive encephalopathy (oculomotor apraxia, epilepsy and ataxia) and systemic manifestations as in type 1 | Ventilatory dysfunction, aspiration pneumonia, and increased risk of interstitial lung disease in homozygotes for L444P mutation |
| Fabry disease | α-galactosidase A | GLA | Renal and cardiac insufficiency, neuropathic pain, angiokeratoma and premature stroke | Wheezing, chronic bronchitis and exercise intolerance |
| Farber lipogranulomatosis | Acid ceramidase | ASAH1 | Joint swelling, subcutaneous nodules and delayed psychomotor development | Aphonia, lower airways infections and fatal respiratory failure |
| Hermansky–Pudlak syndrome | Disrupted biogenesis of lysosome-related organelles | HPS1 | Oculocutaneous albinism, bleeding, diathesis, neutropenia and granulomatous colitis | Pulmonary fibrosis and interstitial lung disease |
| Wolman disease | Deficient activity of lysosomal acid lipase | LIPA | Hepatosplenomegaly, gastrointestinal symptoms and calcified adrenal glands | Pulmonary hypertension |
| Lysinuric protein intolerance | Defective cationic amino acid transport | SLC7A7 | Failure to thrive, osteoporosis, bone marrow anomalies, hepatosplenomegaly, hyperammonaemia, kidney disease and gastrointestinal symptoms | Wheezing, respiratory infections, exercise intolerance, haemoptysis, interstitial lung disease, and pulmonary alveolar proteinosis |
| Glycogenoses | | | | |
| Type Ia | Glucose-6 phosphatase | G6PC | Hepatomegaly, growth retardation, osteopenia, full-cheeked round face, nephromegaly and platelet dysfunction | Pulmonary hypertension |
| Type Ib | Glucose-6 phosphate translocase | SLC37A4 | As type Ia, neutropenia and neutrophil dysfunction | Pulmonary hypertension |
| Type II | α-glucosidase | GAA | Infantile onset: hepatomegaly, feeding difficulties, cardiomegaly and muscle weakness Juvenile and adult-onset: muscle weakness and no cardiac disease | Alveolar hypoventilation and risk of respiratory failure |
| Mucopolysaccharidoses | Lysosomal enzymes in the glycosamino-glycan breakdown pathway | I: IDUA; II: IDS; IIIA: SGSH; IIIB: NAGLU; IIIC: HGSNAT; IIID: GNS; IVA: GALNS; IVB: GLB1; VI: ARSB; VII: GUSB; IX: HYAL1 | Facial dysmorphisms, macrocephaly, dysostosis, joint motion limitation, hepatosplenomegaly, cardiac valve thickening, cardiomegaly and mental retardation (not in all types) | Type I, II, IV and VI: recurrent upper airway infections, obstructive sleep apnoea syndrome and severe respiratory failure |