Lysosomal Storage Disorders Diagnostic Algorithm, Part 2

Clinical information: ■ Developmental delay/Cognitive impairment ■ Coarse features/Organomegaly ■ Dysostosis multiplex ■ Neurodegeneration/Behavioral changes ■ Ichthyosis ■ Hearing defects/loss

LSDS / Lysosomal Storage Disorders Screen, Random, Urine Testing includes: ■ Mucopolysaccharides (MPS) ■ Oligosaccharides (OLIGO) ■ Ceramide trihexosides (CT) ■ Sulfatides (S)

■ OLIGO: ML II/III profile ■ S: abnormal ■ CT and S: abnormal ■ MPS and S: abnormal ■ CT: abnormal ■ OLIGO: characteristic profile ■ CT, MPS and S: normal/abnormal ■ CT, MPS and OLIGO: normal ■ MPS and OLIGO: normal ■ CT and OLIGO: normal ■ MPS, OLIGO and S: normal ■ CT, MPS and S; normal

Mucolipidosis (ML) II/III Metachromatic Prosaposin/ SaposinB Multiple sulfatase deficiency (MSD) Fabry disease leukodystrophy (MLD)

Order BOTH of the following: For recommended diagnostic One of the following One of the following ■ ARSAW / Arylsulfatase A, workup, see Fabry Disease suspected: suspected: Order: GNPTZ / GNPTAB Gene, Order 1 of the following: Leukocytes Diagnostic Testing Algorithm ■ Aspartylglucosaminuria ■ NGLY1 deficiency Full Gene Analysis, Varies ■ ARSAW / Arylsulfatase A, Leukocytes ■ I2SW / Iduronate-2-Sulfatase, ■ α-Mannosidosis (Congenital disorder of ■ ARSU / Arylsulfatase A, 24 Hour, Urine Whole Blood ■ β-Mannosidosis glycosylation: CDG-Iv) ■ Pompe disease ■ MOGS-CDG (CDG-IIb) ■ Sandhoff disease ■ Schindler disease If both results are deficient, ■ Sialidosis MSD confirmed If deficient, If normal, possible Saposin ■ Galactosialidosis* MLD confirmed B or alternate diagnosis ■ α-Fucosidosis* ■ Mucolipidosis II/III* Consider: CDGGP / Congenital ■ GM1 gangliosidosis* Disorders of Glycosylation ■ Morquio A & B* Gene Panel, Varies Consider: ARSAZ / ARSA Consider: PSAP sequencing Consider: SUMFZ / Multiple Sulfatase Gene, Full Gene Analysis, Varies Deficiency, Full Gene Analysis, Varies

Consider: LSDGP / Lysosomal, Storage Disease Gene Panel, Varies

* These conditions may also have elevated MPS