Lysosomal Storage Diseases (LSD) Panel
Lysosomal storage diseases (LSD) are a heterogeneous group of inherited disorders characterized by the accumulation of partially digested or undigested macromolecules in cells, due to the absence of different lysosomal enzymes, which ultimately results in cellular dysfunction and clinical abnormalities 1, 2. To date >50 different LSDs have been described. They affect the central nervous system, skeleton, skin, heart and/or other organs, resulting in specific phenotypic profiles. Based on the type of accumulated substrate, LSDs are classified into different subtypes (Table 1).
Autosomal recessive, X-linked recessive
1/7,100-7,700 (combined for all LSDs) 1, 2, 3
Major clinical symptoms depend on the LSD subtype but in general include the following 1, 2:
- Developmental delay and/or regression
- Progressive neurological features (hypotonia, weakness, seizures, movement disorders, muscle weakness and other)
- Organomegaly (enlarged spleen and liver)
- Pulmonary and cardiac issues
- Dysmorphic features
- Skeletal abnormalities (dysostosis multiplex)
- Visual and/or hearing loss
- Presence of the specific clinical features for each LSD subtype
- Presence of specific accumulated products in serum/ urine
- Absent or reduced e activity of the specific enzyme
- Positive family history of LSD
- Identification of a pathogenic variant in one of the associated genes: AGA, AP3B1, ARSA, ARSB, ASAH1, CLN6, CLN8, CTNS, CTSA, CTSK, FUCA1, GAA, GALC, GALNS, GBA, GLA, GLB1, GM2A, GNPTAB, GNPTG, GNS, GUSB, HEXA, HEXB, HGSNAT, HYAL1, IDS, IDUA, LAMP2, LIPA, LYST, MAN2B1, MANBA, MCOLN1, MLPH, MYO5A, NAGA, NAGLU, NEU1, NPC1, NPC2, NPR2, PPT1, PSAP, RAB27A, SGSH, SLC17A5, SMPD1, SUMF1, TPP1.
Enzyme replacement therapy is available for some LSDs and presents the best therapeutic option when available.
Bone marrow transplantation is a possible option for some LSDs.
Symptomatic treatment can relieve symptoms1, 2:
- Treatment for seizures, cardiac, respiratory and other abnormalities
- Physical/occupational therapy
- Special nutrition/diet depending on the LSD subtype
- Liver transplantation
- Visual, hearing aids, speech therapy, psychotherapy and others
- Urea cycle disorders
- Fatty acid oxidation disorders
- Mitochondrial diseases, CADASIL (Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), Leigh syndrome and others
- Zellweger syndrome, peroxisome biogenesis disorders
- Congenital muscular dystrophies
- Charcot-Marie-Tooth disease
To confirm/establish the diagnosis, CENTOGENE offers the following tests:
- CentoLSD: LSD comprehensive enzyme panel (21 enzymes) with option to reflex to specific genetic testing if an enzyme deficiency is identified
- Lysosomal storage disease NGS Panel: sequencing of the genes AGA, AP3B1, ARSA, ARSB, ASAH1, CLN6, CLN8, CTNS, CTSA, CTSK, FUCA1, GAA, GALC, GALNS, GBA, GLA, GLB1, GM2A, GNPTAB, GNPTG, GNS, GUSB, HEXA, HEXB, HGSNAT, HYAL1, IDS, IDUA, LAMP2, LIPA, LYST, MAN2B1, MANBA, MCOLN1, MLPH, MYO5A, NAGA, NAGLU, NEU1, NPC1, NPC2, NPR2, PPT1, PSAP, RAB27A, SGSH, SLC17A5, SMPD1, SUMF1, TPP1.
- Lysosomal storage disease NGS Panel + CNV: sequencing and additionally detection of large deletions and duplications from the NGS data
- Lysosomal storage disease NGS Panel Genomic:
- Step 1: whole genome sequencing with analysis of only panel genes for sequencing (exonic and intronic) and deletion/duplication variants
- Step 2: if no variant is detected, reflex to bioinformatics analysis of whole genome based on phenotype.
- Individuals with a positive family history of a LSD
- Individuals with symptoms suggestive of a LSD (regardless of family history)
Confirmation of a clinical diagnosis through genetic testing of Lysosomal storage disease can allow for genetic counseling and may direct medical management.