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 type 2 AR 18
ARSA 607574 metachromatic leukodystrophy AR 72
ARSB 611542 mucopolysaccharidosis type VI AR 67
ASAH1 613468 Farber lipogranulomatosis AR 43
CLN6 606725 adulte onset neuronal ceroid lipofuscinosis, Kufs type; neuronal ceroid lipofuscinosis type 6 AR 31
CLN8 607837 neuronal ceroid lipofuscinosis type 8; neuronal ceroid lipofuscinosistype 8, Northern epilepsy variant AR 4
CTNS 606272 ocular nonnephropathic cystinosis; cystinosis; late-onset juvenile or adolescent nephropathic cystinosis AR 10
CTSA 613111 galactosialidosis AR 9
CTSK 601105 pycnodysostosis AR 13
FUCA1 612280 fucosidosis AR 17
GAA 606800 Pompe disease AR 119
GALC 606890 Krabbe disease AR 87
GALNS 612222 mucopolysaccharidosis type IVA AR 160
GBA 606463 Lewy body dementia; susceptibility to late-onset Parkinson disease; Gaucher disease; Gaucher disease type II; Gaucher disease type III; Gaucher disease type IIIC; perinatal lethal Gaucher disease AD, AR 118
GLA 300644 Fabry disease XL 577
GLB1 611458 GM1-gangliosidosis; GM1-gangliosidosis type II; GM1-gangliosidosis type III; mucopolysaccharidosis type IVB AR 85
GM2A 613109 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 13
GUSB 611499 mucopolysaccharidosis type VII AR 27
HEXA 606869 Tay-Sachs disease AR 22
HEXB 606873 Sandhoff disease AR 37
HGSNAT 610453 mucopolysaccharidosis type IIIC; retinitis pigmentosa type 73 AR 31
HYAL1 607071 Mucopolysaccharidosis type IX AR 0
IDS 300823 mucopolysaccharidosis type II XLR 202
IDUA 252800 mucopolysaccharidosis type IH; mucopolysaccharidosis type 1; mucopolysaccharidosis type IS AR 69
LAMP2 309060 Danon disease XLD 10
LIPA 613497 Wolman disease / cholesteryl ester storage disease AR 21
LYST 606897 Chediak-Higashi syndrome AR 31
MAN2B1 609458 alpha-mannosidosis AR 21
MANBA 609489 Mannosidosis, Beta A, Lysosomal AR 11
MCOLN1 605248 Mucolipidosis type IV AR 7
MLPH 606526 Griscelli syndrome, type 3 AR 2
MYO5A 160777 Griscelli syndrome, type 1 AR 31
NAGA 104170 Schindler disease, type I, III AR 7
NAGLU 609701 mucopolysaccharidosis type IIIB; ? axonal Charcot-Marie-Tooth disease type 2V AD, AR 48
NEU1 608272 neuraminidase deficiency AR 7
NPC1 607623 Niemann-Pick disease type C1 AR 233
NPC2 601015 Niemann-Pick disease type C2 AR 16
NPR2 108961 Acromesomelic dysplasia, maroteaux type AD, AR 4
PPT1 600722 neuronal ceroid lipofuscinosis type 1 AR 13
PSAP 176801 metachromatic leukodystrophy due to SAP-b deficiency; atypical Gaucher disease; Combined SAP deficiency; atypical Krabbe disease AR 21
RAB27A 603868 Griscelli syndrome, type 2 AR 6
SGSH 605270 mucopolysaccharidosis type IIIA AR 58
SLC17A5 604322 infantile sialic acid storage disorder; Salla disease AR 7
SMPD1 607608 Niemann-Pick disease type A; Niemann-Pick disease type B AR 69
SUMF1 607939 multiple sulfatase deficiency AR 11
TPP1 607998 neuronal ceroid lipofuscinosis type 2; autosomal recessive spinocerebellar ataxia type 7 AR 23