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Mucopolysaccharidosis, MPS-IV-A(MPS4A)

MedGen UID:
43375
Concept ID:
C0086651
Disease or Syndrome
Synonyms: Galactosamine-6-sulfatase deficiency; Morquio A disease; Morquio syndrome A; Morquio syndrome A, mild; MPS 4A; MPS IVA; MPS4A; Mucopolysaccharidosis type IV A; Mucopolysaccharidosis Type IVA
SNOMED CT: Galactose-6-sulfatase deficiency (7259005); Galactosamine-6-sulfatase deficiency (7259005); MPS IV-A-Mucopolysaccharidosis IV-A (7259005); Mucopolysaccharidosis IV-A (7259005); Morquio syndrome A (7259005); Mucopolysaccharidosis, MPS-IV-A (7259005); Morquio's syndrome, classic form (7259005); N-acetylgalactosamine-6-sulfatase deficiency (7259005); Morquio A syndrome (7259005); Deficiency of chondroitinase (130197005); Deficiency of galactose-6-sulfate sulfatase (130197005); Deficiency of chondroitinsulfatase (130197005); Deficiency of N-acetylgalactosamine-6-sulfatase (130197005)
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).
 
Gene (location): GALNS (16q24.3)
 
Monarch Initiative: MONDO:0009659
OMIM®: 253000
Orphanet: ORPHA309297

Disease characteristics

Excerpted from the GeneReview: Mucopolysaccharidosis Type IVA
The phenotypic spectrum of mucopolysaccharidosis IVA (MPS IVA) is a continuum that ranges from a severe and rapidly progressive early-onset form to a slowly progressive later-onset form. Children with MPS IVA typically have no distinctive clinical findings at birth. The severe form is usually apparent between ages one and three years, often first manifesting as kyphoscoliosis, genu valgum (knock-knee), and pectus carinatum; the slowly progressive form may not become evident until late childhood or adolescence, often first manifesting as hip problems (pain, stiffness, and Legg Perthes disease). Progressive bone and joint involvement leads to short stature, and eventually to disabling pain and arthritis. Involvement of other organ systems can lead to significant morbidity, including respiratory compromise, obstructive sleep apnea, valvular heart disease, hearing impairment, visual impairment from corneal clouding, dental abnormalities, and hepatomegaly. Compression of the spinal cord is a common complication that results in neurologic impairment. Children with MPS IVA have normal intellectual abilities at the outset of the disease. [from GeneReviews]
Authors:
Debra S Regier  |  Matthew Oetgen  |  Pranoot Tanpaiboon   view full author information

Additional descriptions

From OMIM
Mucopolysaccharidosis type IVA is an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system (CNS) involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life (Montano et al., 2008). McKusick (1972) noted that between 1929 and 1959, a miscellany of skeletal disorders was included in the Morquio category, including various types of spondyloepiphyseal dysplasia (see, e.g., 183900) and multiple epiphyseal dysplasia (see, e.g., 132400). Nelson et al. (1988) proposed the division of MPS IVA into 3 subgroups: severe classic, intermediate, and mild, reflecting clinical variability observed in 12 enzymatically proven cases. Those who were only mildly affected showed a relatively high residual enzyme activity.  http://www.omim.org/entry/253000
From MedlinePlus Genetics
In people with MPS IV, the clear covering of the eye (cornea) typically becomes cloudy, which can cause vision loss. Some affected individuals have recurrent ear infections and hearing loss. The airway may become narrow in some people with MPS IV, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). Other common features of this condition include mildly "coarse" facial features, thin tooth enamel, multiple cavities, heart valve abnormalities, a mildly enlarged liver (hepatomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Unlike some other types of mucopolysaccharidosis, MPS IV does not affect intelligence.

The first signs and symptoms of MPS IV usually become apparent during early childhood. Affected individuals develop various skeletal abnormalities, including short stature, knock knees, and abnormalities of the ribs, chest, spine, hips, and wrists. People with MPS IV often have joints that are loose and very flexible (hypermobile), but they may also have restricted movement in certain joints. A characteristic feature of this condition is underdevelopment (hypoplasia) of a peg-like bone in the neck called the odontoid process. The odontoid process helps stabilize the spinal bones in the neck (cervical vertebrae). Odontoid hypoplasia can lead to misalignment of the cervical vertebrae, which may compress and damage the spinal cord, resulting in paralysis or death.

Mucopolysaccharidosis type IV (MPS IV), also known as Morquio syndrome, is a progressive condition that mainly affects the skeleton. The rate at which symptoms worsen varies among affected individuals.

The life expectancy of individuals with MPS IV depends on the severity of symptoms. Severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced. Spinal cord compression and airway obstruction are major causes of death in people with MPS IV.  https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-iv

Clinical features

From HPO
Chondroitin sulfate excretion in urine
MedGen UID:
868657
Concept ID:
C4023059
Finding
An increased concentration of chondroitin sulfate (CHEBI:37397) in the urine.
Keratan sulfate excretion in urine
MedGen UID:
868658
Concept ID:
C4023060
Laboratory or Test Result
An increased concentration of keratan sulfate in the urine.
Ulnar deviation of the wrist
MedGen UID:
115906
Concept ID:
C0231678
Sign or Symptom
Coxa valga
MedGen UID:
116080
Concept ID:
C0239137
Finding
Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults).
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Pointed proximal second through fifth metacarpals
MedGen UID:
340712
Concept ID:
C1854787
Finding
All of the metacarpal bones of the hand have a pointed proximal appearance.
Large elbow
MedGen UID:
903402
Concept ID:
C4280737
Finding
Abnormal increased size of the elbow joint.
Abnormal heart valve morphology
MedGen UID:
892837
Concept ID:
C0241654
Finding
Any structural abnormality of a cardiac valve.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Cervical myelopathy
MedGen UID:
57691
Concept ID:
C0149645
Disease or Syndrome
Waddling gait
MedGen UID:
66667
Concept ID:
C0231712
Finding
Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Lumbar kyphosis
MedGen UID:
336792
Concept ID:
C1844818
Finding
Over curvature of the lumbar region.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Prominent sternum
MedGen UID:
337578
Concept ID:
C1846433
Finding
Disproportionate short-trunk short stature
MedGen UID:
337580
Concept ID:
C1846435
Finding
A type of disproportionate short stature characterized by a short trunk but a average-sized limbs.
Odontoid hypoplasia
MedGen UID:
339524
Concept ID:
C1846439
Finding
The odontoid process, or dens, is a bony projection from the axis (C2) upward into the ring of the atlas (C1) at the top of the spine. During embryogenesis, the body of the odontoid derives from the centrum of the atlas and separates from the atlas, fusing with the superior portion of the axis. If the odontoid is hypoplastic or absent, the attachments for the apical and alar ligaments are missing, allowing for excessive rotation of the atlas, craniocervical instability, and possibly cord compression (summary by Stevens et al., 2009).
Cervical subluxation
MedGen UID:
375973
Concept ID:
C1846798
Finding
A partial dislocation of one or more intervertebral joints in the cervical vertebral column.
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Flaring of rib cage
MedGen UID:
381496
Concept ID:
C1854780
Finding
The presence of wide, concave anterior rib ends.
Constricted iliac wing
MedGen UID:
340710
Concept ID:
C1854785
Finding
Epiphyseal deformities of tubular bones
MedGen UID:
340711
Concept ID:
C1854786
Finding
Ovoid vertebral bodies
MedGen UID:
344549
Concept ID:
C1855665
Finding
When viewed in lateral radiographs, vertebral bodies have a roughly rectangular configuration. This term applies if the vertebral body appears rounded or oval.
Anterior beaking of lumbar vertebrae
MedGen UID:
867183
Concept ID:
C4021541
Anatomical Abnormality
Anterior tongue-like protrusions of the vertebral bodies of the lumbar spine.
Dysostosis multiplex
MedGen UID:
1851010
Concept ID:
C5848292
Disease or Syndrome
Bronchoconstriction
MedGen UID:
36266
Concept ID:
C0079043
Organ or Tissue Function
Tightening of smooth muscle surrounding the bronchi and bronchioles with consequent wheezing and shortness of breath.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Restrictive ventilatory defect
MedGen UID:
478856
Concept ID:
C3277226
Finding
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Widely spaced teeth
MedGen UID:
337093
Concept ID:
C1844813
Finding
Increased spaces (diastemata) between most of the teeth in the same dental arch.
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.
Grayish enamel
MedGen UID:
344367
Concept ID:
C1854783
Finding
A gray discoloration of the dental enamel.
Opacification of the corneal stroma
MedGen UID:
602191
Concept ID:
C0423250
Finding
Reduced transparency of the stroma of cornea.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Mucopolysaccharidosis, MPS-IV-A in Orphanet.

Professional guidelines

PubMed

Olarte-Avellaneda S, Rodríguez-López A, Alméciga-Díaz CJ, Barrera LA
Mol Biol Rep 2014 Nov;41(11):7073-88. Epub 2014 Oct 7 doi: 10.1007/s11033-014-3383-3. PMID: 25287660

Recent clinical studies

Etiology

Szklanny K, Gubrynowicz R, Tylki-Szymańska A
J Appl Genet 2018 Feb;59(1):73-80. Epub 2017 Dec 23 doi: 10.1007/s13353-017-0421-6. PMID: 29275451Free PMC Article

Prognosis

Szklanny K, Gubrynowicz R, Tylki-Szymańska A
J Appl Genet 2018 Feb;59(1):73-80. Epub 2017 Dec 23 doi: 10.1007/s13353-017-0421-6. PMID: 29275451Free PMC Article

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