Publications about genetic testing for metabolic disorders
  1. Lysosomal storage diseases (LSD) panel

Lysosomal storage diseases (LSD) panel

May 30, 2018

Disease summary:

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 Plus: 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 Plus + 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.


Table 1: Overview of genes included in Lysosomal storage diseases panel

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
AGA 613228 Aspartylglucosaminuria AR 0
AP3B1 603401 Hermansky-Pudlak syndrome 2 AR 18
ARSA 607574 Metachromatic leukodystrophy AR 71
ARSB 611542 Mucopolysaccharidosis type VI (Maroteaux-Lamy) AR 66
ASAH1 613468 Spinal muscular atrophy with progressive myoclonic epilepsy; Farber lipogranulomatosis AR 28
CLN6 606725 Ceroid lipofuscinosis, neuronal, Kufs type, adult onset; Ceroid lipofuscinosis, neuronal, 6 AR 30
CLN8 607837 Ceroid lipofuscinosis, neuronal, 8; Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant AR 5
CTNS 606272 Cystinosis, ocular nonnephropathic; Cystinosis, atypical nephropathic; Cystinosis, nephropathic; Cystinosis, late-onset juvenile or adolescent nephropathic AR 10
CTSA 613111 Galactosialidosis AR 9
CTSK 601105 Pycnodysostosis AR 13
FUCA1 612280 Fucosidosis AR 16
GAA 606800 Glycogen storage disease II AR 118
GALC 606890 Krabbe disease AR 89
GALNS 612222 Mucopolysaccharidosis IVA AR 144
GBA 606463 Lewy body dementia, susceptibility to; Parkinson disease, late-onset, susceptibility to; Gaucher disease, type I; Gaucher disease, type II; Gaucher disease, type III; Gaucher disease, type IIIC; Gaucher disease, perinatal lethal AD, AR, Isolated cases, MF 105
GLA 300644 Fabry disease; Fabry disease, cardiac variant XL 529
GLB1 611458 GM1-gangliosidosis, type I; GM1-gangliosidosis, type II; GM1-gangliosidosis, type III; Mucopolysaccharidosis type IVB (Morquio) AR 76
GM2A 613109 GM2-gangliosidosis, AB variant AR 4
GNPTAB 607840 Mucolipidosis II alpha/beta; Mucolipidosis III alpha/beta AR 29
GNPTG 607838 Mucolipidosis III gamma AR 6
GNS 607664 Mucopolysaccharidosis type IIID AR 12
GUSB 611499 Mucopolysaccharidosis VII AR 26
HEXA 606869 GM2-gangliosidosis, several forms; [Hex A pseudodeficiency]; Tay-Sachs disease AR 19
HEXB 606873 Sandhoff disease, infantile, juvenile, and adult forms AR 38
HGSNAT 610453 Mucopolysaccharidosis type IIIC (Sanfilippo C); Retinitis pigmentosa 73 AR 29
HYAL1 607071 ?Mucopolysaccharidosis type IX AR 0
IDS 300823 Mucopolysaccharidosis II XL R 190
IDUA 252800 Mucopolysaccharidosis Ih; Mucopolysaccharidosis Ih/s; Mucopolysaccharidosis Is AR 59
LAMP2 309060 Danon disease XL D 10
LIPA 613497 Cholesteryl ester storage disease; Wolman disease AR 20
LYST 606897 Chediak-Higashi syndrome AR 30
MAN2B1 609458 Mannosidosis, alpha-, types I and II AR 19
MANBA 609489 Mannosidosis, beta AR 9
MCOLN1 605248 Mucolipidosis IV AR 6
MLPH 606526 Griscelli syndrome, type 3 AR 2
MYO5A 160777 Griscelli syndrome, type 1 AR 31
NAGA 104170 Schindler disease, type I; Schindler disease, type III; Kanzaki disease AR 7
NAGLU 609701 Mucopolysaccharidosis type IIIB (Sanfilippo B); ?Charcot-Marie-Tooth disease, axonal, type 2V AD, AR 43
NEU1 608272 Sialidosis, type I; Sialidosis, type II AR 7
NPC1 607623 Niemann-Pick disease, type C1; Niemann-Pick disease, type D AR 221
NPC2 601015 Niemann-pick disease, type C2 AR 14
NPR2 108961 Acromesomelic dysplasia, Maroteaux type; Epiphyseal chondrodysplasia, Miura type; Short stature with nonspecific skeletal abnormalities AD, AR 4
PPT1 600722 Ceroid lipofuscinosis, neuronal, 1 AR 12
PSAP 176801 Metachromatic leukodystrophy due to SAP-b deficiency; Gaucher disease, atypical; Combined SAP deficiency; Krabbe disease, atypical AR 21
RAB27A 603868 Griscelli syndrome, type 2 AR 7
SGSH 605270 Mucopolysaccharidosis type IIIA (Sanfilippo A) AR 54
SLC17A5 604322 Sialic acid storage disorder, infantile; Salla disease AR 7
SMPD1 607608 Niemann-Pick disease, type A; Niemann-Pick disease, type B AR 64
SUMF1 607939 Multiple sulfatase deficiency AR 11
TPP1 607998 Ceroid lipofuscinosis, neuronal, 2; Spinocerebellar ataxia, autosomal recessive 7 AR 21