Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

Combined deficiency of sialidase AND beta galactosidase(GSL)

MedGen UID:: 82779
•Concept ID:: C0268233
•: Disease or Syndrome

Synonyms:	CATHEPSIN A DEFICIENCY; Cathepsin A deficiency of; Galactosialidosis; Goldberg syndrome; GSL; Lysosomal protective protein deficiency of; Neuraminidase deficiency with beta-galactosidase deficiency; Neuraminidase/beta-galactosidase expression; Protective protein/Cathepsin A deficiency
SNOMED CT:	GSL - Galactosialidosis (35691006); Protective protein deficiency (35691006); Combined deficiency of neuroaminidase and beta galactosidase (35691006); Combined deficiency of sialidase AND beta galactosidase (35691006); Neuraminidase deficiency with beta-galactosidase deficiency (35691006); Goldberg syndrome (35691006); Galactosialidosis (35691006)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	CTSA (20q13.12)

Monarch Initiative:	MONDO:0009737
OMIM®:	256540
Orphanet:	ORPHA351

Definition

Galactosialidosis (GSL) is a lysosomal storage disease associated with a combined deficiency of beta-galactosidase (611458) and neuraminidase (608272), secondary to a defect in protective protein/cathepsin A (PPCA). All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and rare occurrence of neurologic signs. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival. The majority of reported patients belong to the juvenile/adult group and are mainly of Japanese origin (summary by d'Azzo et al., 2001). [from OMIM]

Additional description

From MedlinePlus Genetics
Galactosialidosis is a condition that affects many areas of the body. The three forms of galactosialidosis are distinguished by the age at which symptoms develop and the pattern of features.

The early infantile form of galactosialidosis is associated with extensive swelling caused by fluid accumulation before birth (hydrops fetalis), a soft out-pouching in the lower abdomen (an inguinal hernia), and an enlarged liver and spleen (hepatosplenomegaly). Additional features of this form include abnormal bone development (dysostosis multiplex) and distinctive facial features that are often described as "coarse." Some infants have an enlarged heart (cardiomegaly), an eye abnormality called a cherry-red spot, and kidney disease that can progress to kidney failure. Infants with this form usually are diagnosed between birth and 3 months of age; they typically live to around 6 months of age.

The late infantile form of galactosialidosis shares some features with the early infantile form, although the signs and symptoms are somewhat less severe and begin later in infancy. This form is characterized by short stature, dysostosis multiplex, heart valve problems, hepatosplenomegaly, and "coarse" facial features. Other symptoms seen in some individuals with this type include intellectual disabilities, hearing loss, and a cherry-red spot. Children with this condition typically develop symptoms around 2 years old. The life expectancy of individuals with this type varies depending on the severity of symptoms.

The juvenile/adult form of galactosialidosis has signs and symptoms that are somewhat different from those of the other two types. This form is distinguished by difficulty coordinating movements (ataxia), muscle twitches (myoclonus), seizures, and intellectual disabilities that worsen over time. People with this form typically also have dark red spots on the skin (angiokeratomas), abnormalities in the bones of the spine, "coarse" facial features, a cherry-red spot, vision loss, and hearing loss. The age at which symptoms begin to develop varies widely among affected individuals, but the average age is 16. This form is typically associated with a nearly normal life expectancy. https://medlineplus.gov/genetics/condition/galactosialidosis

Clinical features

From HPO

Hemangioma

MedGen UID:: 5477
•Concept ID:: C0018916
•: Neoplastic Process

A hemangioma is a benign tumor characterized by blood-filled spaces lined by benign endothelial cells. A hemangioma characterized by large endothelial spaces (caverns) is called a cavernous hemangioma (in contrast to a hemangioma with small endothelial spaces, which is called capillary hemangioma).

See: Feature record | Search on this feature

Cherry red spot of the macula

MedGen UID:: 786046
•Concept ID:: C2216370
•: Finding

Pallor of the perifoveal macula of the retina with appearance of a small circular reddish choroid shape as seen through the fovea centralis due to relative transparency of the macula.

See: Feature record | Search on this feature

Severe short stature

MedGen UID:: 3931
•Concept ID:: C0013336
•: Disease or Syndrome

A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.

See: Feature record | Search on this feature

Hepatosplenomegaly

MedGen UID:: 9225
•Concept ID:: C0019214
•: Sign or Symptom

Simultaneous enlargement of the liver and spleen.

See: Feature record | Search on this feature

Visceromegaly

MedGen UID:: 22659
•Concept ID:: C0042782
•: Pathologic Function

Abnormal increased size of the viscera of the abdomen.

See: Feature record | Search on this feature

Hearing impairment

MedGen UID:: 235586
•Concept ID:: C1384666
•: Disease or Syndrome

A decreased magnitude of the sensory perception of sound.

See: Feature record | Search on this feature

Seizure

MedGen UID:: 20693
•Concept ID:: C0036572
•: Sign or Symptom

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

See: Feature record | Search on this feature

Intellectual disability

MedGen UID:: 811461
•Concept ID:: C3714756
•: Mental or Behavioral Dysfunction

Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

See: Feature record | Search on this feature

Dysostosis multiplex

MedGen UID:: 1851010
•Concept ID:: C5848292
•: Disease or Syndrome

See: Feature record | Search on this feature

Decreased beta-galactosidase activity

MedGen UID:: 383939
•Concept ID:: C1856559
•: Finding

Abnormally decreased rate of beta-galactosidase activity. Beta-galactosidase activity can be measured in leukocyte, fibroblast, or plasma.

See: Feature record | Search on this feature

Coarse facial features

MedGen UID:: 335284
•Concept ID:: C1845847
•: Finding

Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.

See: Feature record | Search on this feature

Conjunctival telangiectasia

MedGen UID:: 66780
•Concept ID:: C0239105
•: Disease or Syndrome

The presence of small (ca. 0.5-1.0 mm) dilated blood vessels near the surface of the mucous membranes of the conjunctiva.

See: Feature record | Search on this feature

Non-immune hydrops fetalis

MedGen UID:: 105327
•Concept ID:: C0455988
•: Disease or Syndrome

Hydrops fetalis is a descriptive term for generalized edema of the fetus, with fluid accumulation in extravascular components and body cavities. It is not a diagnosis in itself, but a symptom and end-stage result of a wide variety of disorders. In the case of immune hydrops fetalis, a frequent cause is maternofetal incompatibility as in that related to a number of genetic anemias and metabolic disorders expressed in the fetus; in other instances, it remains idiopathic and likely multifactorial (summary by Bellini et al., 2009). Nonimmune hydrops fetalis accounts for 76 to 87% of all described cases of hydrops fetalis (Bellini et al., 2009). Genetic Heterogeneity of Hydrops Fetalis In southeast Asia, alpha-thalassemia (604131) is the most common cause of hydrops fetalis, accounting for 60 to 90% of cases. Almost all of these cases result from homozygous deletion of the HBA1 (141800) and HBA2 (141850) genes. A few cases have been reported that had 1 apparently normal alpha-globin gene, termed the hemoglobin H (613978) hydrops fetalis syndrome (summary by Chui and Waye, 1998). Other genetic disorders predisposing to NIHF include other congenital anemias, such as erythropoietic porphyria (e.g., 606938.0013), and many metabolic disorders, such as one form of Gaucher disease (e.g., 606463.0009), infantile sialic acid storage disease (269920), mucopolysaccharidosis type VII (253220), glycogen storage disease IV (232500), congenital disorder of glycosylation type Ia (212065), and disorders of lymphatic malformation (see, e.g., LMPHM1, 153100).

See: Feature record | Search on this feature

Opacification of the corneal stroma

MedGen UID:: 602191
•Concept ID:: C0423250
•: Finding

Reduced transparency of the stroma of cornea.

See: Feature record | Search on this feature

Show all Hide all

Abnormality of head or neck
- Coarse facial features
Abnormality of metabolism/homeostasis
- Decreased beta-galactosidase activity
Abnormality of prenatal development or birth
- Non-immune hydrops fetalis
Abnormality of the cardiovascular system
- Cherry red spot of the macula
Abnormality of the digestive system
- Hepatosplenomegaly
- Visceromegaly
Abnormality of the eye
- Opacification of the corneal stroma
Abnormality of the integument
- Conjunctival telangiectasia
Abnormality of the musculoskeletal system
- Dysostosis multiplex
Abnormality of the nervous system
- Intellectual disability
- Seizure
Ear malformation
- Hearing impairment
Growth abnormality
- Severe short stature
Neoplasm
- Hemangioma

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVCombined deficiency of sialidase AND beta galactosidase

Congenital, Hereditary, and Neonatal Diseases and Abnormalities
- Inborn genetic diseases
  - Inborn errors of metabolism
    - Lysosomal storage disease
      - Combined deficiency of sialidase AND beta galactosidase

Follow this link to review classifications for Combined deficiency of sialidase AND beta galactosidase in Orphanet.

Professional guidelines

PubMed

Chemical chaperone treatment for galactosialidosis: Effect of NOEV on β-galactosidase activities in fibroblasts.

Hossain MA, Higaki K, Shinpo M, Nanba E, Suzuki Y, Ozono K, Sakai N
Brain Dev 2016 Feb;38(2):175-80. Epub 2015 Aug 7 doi: 10.1016/j.braindev.2015.07.006. PMID: 26259553

See all (1)