Table 1.

Comparative Features in Renal Phospholipidosis from Selected Etiologies.

	Fabry disease	Drug-induced phospholipidosis	Nail-Patella syndrome and isolated LMX1B-associated nephropathy in the absence of extrarenal manifestations17	Niemann-Pick type A/B	Niemann-Pick type C
Selected clinical findings	• Angiokeratoma • Acroparesthesia • Proteinuria • Kidney failure • Cardiomyopathy • Cornea verticillata • Cardiac arrhythmia • Elevated globotriaosylsphingosine (LysoGb3)	• Cornea verticillata (in amiodarone case). • Proteinuria • Kidney failure	• Nail-Patella syndrome • Usually apparent at birth or during early childhood • Nails dysplasia (98%) • Aplasia or hypoplasia of patellae • Glaucoma • Lester’s sign (cloverleaf shape discoloration of iris) • Nephropathy (30%-50%) • Hematuria • Kidney failure (5%) • Isolated LMX1B-associated nephropathy in the absence of extrarenal manifestations • Microscopic hematuria • Proteinuria	Type A or infantile neurovisceral form with very low acid sphingomyelinase activity and usually fatal by the age of 3 Type B Hepatosplenomegaly Thrombocytopenia Interstitial lung disease Neurological involvement	Early infantile (2 months to 2 years) Hepatosplenomegaly Neurologic involvement such as delay developmental milestone and central hypotonia Late infantile (2-6 years) Isolated splenomegaly Hepatosplenomegaly Neurologic involvement VSGP Epilepsy Juvenile (6-15 years) classical form Isolated splenomegaly (rarely hepatosplenomagaly) VSGP Cataplexy Ataxia Adolescent and adults (>15 years) splenomegaly VSGP Psychosis, depression Cerebellar ataxia Dysphagia
Genetic mutations	GLA (α-galactosidase -A)gene	None	LMX1B	SMPD1 (sphingomyelin phosphodiesterase1)	NPC1 (95%) NPC2 (5%)
Transmission	X-linked recessive	None	Autosomal dominant	Autosomal recessive	Autosomal recessive
Defect	Decrease in α-galactosidase A activity	Chloroquine has been shown to cause direct suppression of α-galactosidase A activity. Amiodarone been shown to inhibit phospholipase A1 and A2 activity in vitro	LMX1B encodes an LIM-homeodomain protein critical for limb, kidney, and eye development	Decrease in acid sphingomyelinase A activity	Impairment in processing and utilization of endocytosed cholesterol
Electron microscopic findings	LB are more extensively present in various types of renal cells including podocytes, tubular epithelium, vascular endothelial cells, and medial smooth muscle cells	Müller-Höcker et al described curvilinear inclusions in podocytes and vascular smooth muscle cells in chloroquine case Curvilinear inclusions also found in podocytes, tubular cells, glomerular endothelium, and vascular smooth muscle cells in hydroxychloroquine case In amiodarone case: LB identified in podocytes, mesangial cells, and tubular epithelial cells with no inclusions identified in endothelial cells LB in various renal cell types were described in other cases of drug induced renal phospholipidosis	Pinto e Vairo et al18 described LB in podocytes. No LB in endothelial cells, mesangial cells, peritubular capillaries, or tubular cells	LB identified in podocytes, tubular epithelial cells, peritubular capillaries, endothelial cells, and many small nerves. LB were not present in glomerular endothelial cells	LB identified in most podocytes and focal tubular epithelial cells and not present in other cell types in the tissue available for electron microscopy

Note. The bold letter signified a different entities. VSGP = vertical supranuclear gaze palsy; GLA = galactosidase-alpha; LB = lamellar bodies.