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Hurler syndrome(MPS1-H)

MedGen UID:
39698
Concept ID:
C0086795
Disease or Syndrome
Synonyms: Gargoylism, Hurler Syndrome; MUCOPOLYSACCHARIDOSIS TYPE IH
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Mucopolysaccharidosis, MPS-I-H (65327002); L-iduronidase deficiency, Hurler type (65327002); Lipochondrodystrophy (65327002); Gargoylism (65327002); Hurler's syndrome (65327002); Hurler-Pfaundler syndrome (65327002); Dysostosis multiplex syndrome (65327002); Dysostosis multiplex (254069004); MPS 1-H - Mucopolysaccharidosis type I-H (65327002); Mucopolysaccharidosis type I-H (65327002); Hurler disease MPS type 1H (65327002); Mucopolysaccharidosis type I severe form (65327002)
 
Gene (location): IDUA (4p16.3)
OMIM®: 607014
HPO: HP:0000943
Orphanet: ORPHA93473

Disease characteristics

Excerpted from the GeneReview: Mucopolysaccharidosis Type I
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having either severe or attenuated MPS I, a distinction that influences therapeutic options. Severe MPS I. Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory-tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal. By age three years, linear growth decreases. Intellectual disability is progressive and profound. Hearing loss is common. Death, typically caused by cardiorespiratory failure, usually occurs within the first ten years of life. Attenuated MPS I. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities can be present. Clinical onset is usually between ages three and ten years. Hearing loss and cardiac valvular disease are common. [from GeneReviews]
Authors:
Lorne A Clarke   view full author information

Additional description

From OMIM
The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function. Deficiency of alpha-L-iduronidase can result in a wide range of phenotypic involvement with 3 major recognized clinical entities: Hurler (MPS IH), Scheie (MPS IS; 607016), and Hurler-Scheie (MPS IH/S; 607015) syndromes. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression (McKusick, 1972). MPS I is more frequent than MPS II (Hunter syndrome; 309900), which has no corneal clouding and pursues a slower course.  http://www.omim.org/entry/607014

Clinical features

Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Hernia
MedGen UID:
6816
Concept ID:
C0019270
Finding
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Disease or Syndrome
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Finding
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Autosomal recessive nonsyndromic hydrocephalus is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012). Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (307000), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (100800) and in Hurler disease (607014). Genetic Heterogeneity of Congenital Hydrocephalus See also autosomal recessive HYC2 (615219), caused by mutation in the MPDZ gene (603785) on chromosome 9p. An X-linked form (307000) is caused by mutation in the L1CAM gene on (308840) on chromosome Xq28.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Hurler syndrome
MedGen UID:
39698
Concept ID:
C0086795
Disease or Syndrome
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having eithersevereorattenuatedMPS I, a distinction that influences therapeutic options.Severe MPS I.Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory-tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal. By age three years, linear growth decreases. Intellectual disability is progressive and profound. Hearing loss is common. Death, typically caused by cardiorespiratory failure, usually occurs within the first ten years of life.Attenuated MPS I.The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities can be present. Clinical onset is usually between ages three and ten years. Hearing loss and cardiac valvular disease are common.
Joint stiffness
MedGen UID:
56403
Concept ID:
C0162298
Sign or Symptom
Coxa valga
MedGen UID:
116080
Concept ID:
C0239137
Finding
Microdontia
MedGen UID:
66008
Concept ID:
C0240340
Congenital Abnormality
Enlarged tonsils
MedGen UID:
78800
Concept ID:
C0272386
Disease or Syndrome
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Gingival overgrowth
MedGen UID:
87712
Concept ID:
C0376480
Finding
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
Opacification of the corneal stroma
MedGen UID:
602191
Concept ID:
C0423250
Finding
Reduced transparency of the stroma of cornea.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Short clavicles
MedGen UID:
96529
Concept ID:
C0426799
Congenital Abnormality
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
Recurrent ear infections
MedGen UID:
473277
Concept ID:
C0743360
Finding
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
Diaphyseal thickening
MedGen UID:
331984
Concept ID:
C1835473
Finding
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Thick vermilion border
MedGen UID:
332232
Concept ID:
C1836543
Finding
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
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).
J-shaped sella turcica
MedGen UID:
381480
Concept ID:
C1854718
Finding
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
Biconcave vertebral bodies
MedGen UID:
383834
Concept ID:
C1856087
Finding
Hypoplasia of the femoral head
MedGen UID:
384014
Concept ID:
C1856920
Finding
Calvarial hyperostosis
MedGen UID:
350147
Concept ID:
C1863351
Finding
Flared iliac wings
MedGen UID:
356097
Concept ID:
C1865841
Finding
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Abnormal CNS myelination
MedGen UID:
866800
Concept ID:
C4021152
Anatomical Abnormality
Constrictive median neuropathy
MedGen UID:
868610
Concept ID:
C4023009
Anatomical Abnormality
Urinary glycosaminoglycan excretion
MedGen UID:
871129
Concept ID:
C4025598
Finding
Increased head circumference
MedGen UID:
909477
Concept ID:
C4083076
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Hurler syndrome in Orphanet.

Conditions with this feature

Fucosidosis
MedGen UID:
5288
Concept ID:
C0016788
Disease or Syndrome
Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Fucosidosis has been classified into 2 major types. Type 1 is characterized by rapid psychomotor regression and severe neurologic deterioration beginning at about 6 months of age, elevated sweat sodium chloride, and death within the first decade of life. Type 2 is characterized by milder psychomotor retardation and neurologic signs, the development of angiokeratoma corporis diffusum, normal sweat salinity, and longer survival (Kousseff et al., 1976).
Deficiency of alpha-mannosidase
MedGen UID:
7467
Concept ID:
C0024748
Disease or Syndrome
Alpha-mannosidosis encompasses a continuum of clinical findings from mild to severe. Clinical subtypes include the following: A mild form recognized after age ten years with absence of skeletal abnormalities, myopathy, and slow progression (type 1). A moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression (type 2). A severe form manifesting as prenatal loss or early death from progressive central nervous system involvement (type 3). Individuals with a milder phenotype have mild-to-moderate intellectual disability, impaired hearing, characteristic coarse features, clinical or radiographic skeletal abnormalities, immunodeficiency, and primary central nervous system disease, mainly cerebellar involvement causing ataxia. Periods of psychiatric symptoms are common. Associated medical problems can include corneal opacities, hepatosplenomegaly, aseptic destructive arthritis, and metabolic myopathy. Alpha-mannosidosis is insidiously progressive; some individuals may live into the sixth decade.
Mucopolysaccharidosis, MPS-II
MedGen UID:
7734
Concept ID:
C0026705
Disease or Syndrome
Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycans (GAG) accumulation. The vast majority of affected individuals are male; on rare occasion heterozygous females manifest findings. Age of onset, disease severity, and rate of progression vary significantly among affected males. In those with early progressive disease, CNS involvement (manifest primarily by progressive cognitive deterioration), progressive airway disease, and cardiac disease usually result in death in the first or second decade of life. In those with slowly progressive disease, the CNS is not (or is minimally) affected, although the effect of GAG accumulation on other organ systems may be early progressive to the same degree as in those who have progressive cognitive decline. Survival into the early adult years with normal intelligence is common in the slowly progressing form of the disease. Additional findings in both forms of MPS II include: short stature; macrocephaly with or without communicating hydrocephalus; macroglossia; hoarse voice; conductive and sensorineural hearing loss; hepato-splenomegaly; dysostosis multiplex; spinal stenosis; and carpal tunnel syndrome.
Mucopolysaccharidosis type VI
MedGen UID:
44514
Concept ID:
C0026709
Disease or Syndrome
Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Clinical features and severity are variable, but usually include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism. Intelligence is usually normal (Azevedo et al., 2004).
Pseudo-Hurler polydystrophy
MedGen UID:
10988
Concept ID:
C0033788
Disease or Syndrome
Mucolipidosis alpha/beta (ML III alpha/beta; pseudo-Hurler polydystrophy), a slowly progressive disorder with clinical onset at approximately age three years, is characterized by slow growth rate and subnormal stature; radiographic evidence of mild to moderate dysostosis multiplex; joint stiffness and pain initially in the shoulders, hips, and fingers; gradual mild coarsening of facial features; and normal to mildly impaired cognitive development. If present, organomegaly is mild. Pain from osteoporosis that is clinically and radiologically apparent in childhood becomes more severe from adolescence. Cardiorespiratory complications (restrictive lung disease, thickening and insufficiency of the mitral and aortic valves, left and/or right ventricular hypertrophy) are common causes of death, typically in early to middle adulthood.
Mucopolysaccharidosis type VII
MedGen UID:
43108
Concept ID:
C0085132
Disease or Syndrome
Mucopolysaccharidosis type VII is an autosomal recessive lysosomal storage disease characterized by the inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment (Shipley et al., 1993). MPS VII was the first autosomal mucopolysaccharidosis for which chromosomal assignment was achieved.
Mucopolysaccharidosis, MPS-I-H/S
MedGen UID:
88566
Concept ID:
C0086431
Disease or Syndrome
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having eithersevereorattenuatedMPS I, a distinction that influences therapeutic options.Severe MPS I.Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory-tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal. By age three years, linear growth decreases. Intellectual disability is progressive and profound. Hearing loss is common. Death, typically caused by cardiorespiratory failure, usually occurs within the first ten years of life.Attenuated MPS I.The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities can be present. Clinical onset is usually between ages three and ten years. Hearing loss and cardiac valvular disease are common.
Mucopolysaccharidosis, MPS-III-A
MedGen UID:
39264
Concept ID:
C0086647
Disease or Syndrome
The Sanfilippo syndrome, or mucopolysaccharidosis III, is an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate (Esposito et al., 2000). The disorder is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. Type A has been reported (van de Kamp et al., 1981) to be the most severe, with earlier onset and rapid progression of symptoms and shorter survival. Genetic Heterogeneity of Mucopolysaccharidosis Type III MPS III includes 4 types, each due to the deficiency of a different enzyme: heparan N-sulfatase (type A); alpha-N-acetylglucosaminidase (type B; 252920); acetyl CoA:alpha-glucosaminide acetyltransferase (type C; 252930); and N-acetylglucosamine 6-sulfatase (type D; 252940).
Mucopolysaccharidosis, MPS-III-B
MedGen UID:
88601
Concept ID:
C0086648
Disease or Syndrome
Sanfilippo syndrome B is an autosomal recessive lysosomal storage disorder characterized by the accumulation of heparan sulfate. Clinically, patients have progressive neurodegeneration, behavioral problems, mild skeletal changes, and shortened life span. The clinical severity ranges from mild to severe (Chinen et al., 2005). For a phenotypic description and a discussion of genetic heterogeneity of Sanfilippo syndrome, or mucopolysaccharidosis III, see MPS IIIA (252900).
Mucopolysaccharidosis, MPS-III-C
MedGen UID:
39477
Concept ID:
C0086649
Disease or Syndrome
Sanfilippo syndrome comprises several forms of lysosomal storage diseases due to impaired degradation of heparan sulfate. The deficient enzyme in Sanfilippo syndrome C, or MPS IIIC, is an acetyltransferase that catalyzes the conversion of alpha-glucosaminide residues to N-acetylglucosaminide in the presence of acetyl-CoA. For a general phenotypic description and a discussion of genetic heterogeneity of Sanfilippo syndrome, see MPS IIIA (252900).
Mucopolysaccharidosis, MPS-III-D
MedGen UID:
88602
Concept ID:
C0086650
Disease or Syndrome
The mucopolysaccharidoses are a family of lysosomal storage diseases caused by deficiencies of enzymes required for the catabolism of glycosaminoglycans. The defects result in accumulation of excessive intralysosomal glycosoaminoglycans (mucopolysaccharides) in various tissues, causing distended lysosomes to accumulate in the cell and interfere with cell function. Multiple types have been described (Mok et al., 2003).
Hurler syndrome
MedGen UID:
39698
Concept ID:
C0086795
Disease or Syndrome
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having eithersevereorattenuatedMPS I, a distinction that influences therapeutic options.Severe MPS I.Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory-tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal. By age three years, linear growth decreases. Intellectual disability is progressive and profound. Hearing loss is common. Death, typically caused by cardiorespiratory failure, usually occurs within the first ten years of life.Attenuated MPS I.The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities can be present. Clinical onset is usually between ages three and ten years. Hearing loss and cardiac valvular disease are common.
Aspartylglycosaminuria
MedGen UID:
78649
Concept ID:
C0268225
Disease or Syndrome
Aspartylglucosaminuria is a severe autosomal recessive lysosomal storage disorder that involves the central nervous system and causes skeletal abnormalities as well as connective tissue lesions. The most characteristic feature is progressive mental retardation. The disorder is caused by deficient activity of the lysosomal enzyme glycosylasparaginase, which results in body fluid and tissue accumulation of a series of glycoasparagines, i.e., glycoconjugates with an aspartylglucosamine moiety at the reducing end. AGU belongs to the group of disorders commonly referred to as the Finnish disease heritage (summary by Mononen et al., 1993 and Arvio and Arvio, 2002).
Sialidosis, type II
MedGen UID:
120621
Concept ID:
C0268226
Disease or Syndrome
Sialidosis is an autosomal recessive disorder characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by a deficiency of the enzyme neuraminidase. Common to the sialidoses is the accumulation and/or excretion of sialic acid (N-acetylneuraminic acid) covalently linked ('bound') to a variety of oligosaccharides and/or glycoproteins (summary by Lowden and O'Brien, 1979). The sialidoses are distinct from the sialurias in which there is storage and excretion of 'free' sialic acid, rather than 'bound' sialic acid; neuraminidase activity in sialuria is normal or elevated. Salla disease (604369) is a form of 'free' sialic acid disease. Classification Lowden and O'Brien (1979) provided a logical nosology of neuraminidase deficiency into sialidosis type I and type II. Type I is the milder form, also known as the 'normosomatic' type or the cherry red spot-myoclonus syndrome. Sialidosis type II is the more severe form with an earlier onset, and is also known as the 'dysmorphic' type. Type II has been subdivided into juvenile and infantile forms. Other terms for sialidosis type II are mucolipidosis I and lipomucopolysaccharidosis.
Combined deficiency of sialidase AND beta galactosidase
MedGen UID:
82779
Concept ID:
C0268233
Disease or Syndrome
Galactosialidosis 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).
Multiple sulfatase deficiency
MedGen UID:
75664
Concept ID:
C0268263
Disease or Syndrome
Multiple sulfatase deficiency is an autosomal recessive inborn error of metabolism resulting in tissue accumulation of sulfatides, sulfated glycosaminoglycans, sphingolipids, and steroid sulfates. The enzymatic defect affects the whole family of sulfatase enzymes; thus, the disorder combines features of metachromatic leukodystrophy (250100) and of various mucopolysaccharidoses (see, e.g., MPS6; 253200). Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and ichthyosis. Different types of MSD can be distinguished according to the age of onset: neonatal, late infantile (0 to 2 years), and juvenile (2 to 4 years). Neonatal MSD is the most severe form with a broad range of mucopolysaccharidosis-like symptoms and death within the first year of life. Late-infantile MSD, which includes the majority of cases, resembles late-infantile metachromatic leukodystrophy with progressive loss of mental and motor abilities and skeletal changes. There is also an attenuated form of late-infantile MSD with onset beyond the second year of life. Rare cases of juvenile-onset MSD have been reported with onset of symptoms in late childhood and slower progression (Blanco-Aguirre et al., 2001) (summary by Schlotawa et al., 2011).
Mucolipidosis III Gamma
MedGen UID:
340743
Concept ID:
C1854896
Disease or Syndrome
Mucolipidosis III gamma (ML III gamma) is a slowly progressive disorder characterized by childhood onset of radiographic evidence of mild to moderate dysostosis multiplex; joint stiffness and pain initially in the shoulders, hips, and fingers; and gradual mild coarsening of facial features. Cardiorespiratory complications (restrictive lung disease, thickening and insufficiency of the mitral and aortic valves, left ventricular hypertrophy) can be significant. A few affected individuals have mild cognitive impairment. Because ML III gamma has only recently been distinguished from the more common ML III alpha/beta, previously published descriptions of ML III may have inadvertently included both of these disorders. Thus, much is to yet be learned about the specific manifestations and natural history of ML III gamma.
Mucopolysaccharidosis-plus syndrome
MedGen UID:
934594
Concept ID:
C4310627
Disease or Syndrome
MPSPS is an autosomal recessive inborn error of metabolism resulting in a multisystem disorder with features of the mucopolysaccharidosis lysosomal storage diseases (see, e.g., 607016). Patients present in infancy or early childhood with respiratory difficulties, cardiac problems, anemia, dysostosis multiplex, renal involvement, coarse facies, and delayed psychomotor development. Most patients die of cardiorespiratory failure in the first years of life (summary by Kondo et al., 2017).

Recent clinical studies

Etiology

Kiely BT, Kohler JL, Coletti HY, Poe MD, Escolar ML
Orphanet J Rare Dis 2017 Feb 14;12(1):32. doi: 10.1186/s13023-017-0583-7. PMID: 28193245Free PMC Article
Schmidt M, Breyer S, Löbel U, Yarar S, Stücker R, Ullrich K, Müller I, Muschol N
Orphanet J Rare Dis 2016 Jul 8;11(1):93. doi: 10.1186/s13023-016-0470-7. PMID: 27392569Free PMC Article
Kennedy J, Noel J, O'Meara A, Mulhall K, Crushell E, Fogarty E, Kelly P
J Pediatr Orthop 2016 Jan;36(1):25-8. doi: 10.1097/BPO.0000000000000385. PMID: 26090987
Schwinger W, Sovinz P, Benesch M, Lackner H, Seidel M, Strenger V, Sperl D, Raicht A, Brunner-Krainz M, Paschke E, Plecko B, Urban C
Pediatr Hematol Oncol 2014 Nov;31(8):723-30. Epub 2014 Aug 12 doi: 10.3109/08880018.2014.939794. PMID: 25116402
Yasin MN, Sacho R, Oxborrow NJ, Wraith JE, Williamson JB, Siddique I
Spine (Phila Pa 1976) 2014 Mar 1;39(5):381-7. doi: 10.1097/BRS.0000000000000157. PMID: 24573070

Diagnosis

Lukefahr AL, Proytcheva M
J Pediatr Hematol Oncol 2018 Jan;40(1):74-75. doi: 10.1097/MPH.0000000000001041. PMID: 29200150
Kiely BT, Kohler JL, Coletti HY, Poe MD, Escolar ML
Orphanet J Rare Dis 2017 Feb 14;12(1):32. doi: 10.1186/s13023-017-0583-7. PMID: 28193245Free PMC Article
Thakur AR, Naikmasur VG, Sattur A
Skeletal Radiol 2015 Apr;44(4):579-86. Epub 2014 Aug 20 doi: 10.1007/s00256-014-1982-7. PMID: 25134498
Poe MD, Chagnon SL, Escolar ML
Ann Neurol 2014 Nov;76(5):747-53. Epub 2014 Oct 8 doi: 10.1002/ana.24246. PMID: 25103575
Yasin MN, Sacho R, Oxborrow NJ, Wraith JE, Williamson JB, Siddique I
Spine (Phila Pa 1976) 2014 Mar 1;39(5):381-7. doi: 10.1097/BRS.0000000000000157. PMID: 24573070

Therapy

Liang J, Singhal A
J Neurosurg Pediatr 2016 May;17(5):537-9. Epub 2016 Jan 8 doi: 10.3171/2015.9.PEDS15477. PMID: 26745646
Schwinger W, Sovinz P, Benesch M, Lackner H, Seidel M, Strenger V, Sperl D, Raicht A, Brunner-Krainz M, Paschke E, Plecko B, Urban C
Pediatr Hematol Oncol 2014 Nov;31(8):723-30. Epub 2014 Aug 12 doi: 10.3109/08880018.2014.939794. PMID: 25116402
El-Amouri SS, Dai M, Han JF, Brady RO, Pan D
Mol Ther 2014 Dec;22(12):2028-37. Epub 2014 Aug 4 doi: 10.1038/mt.2014.152. PMID: 25088464Free PMC Article
Boelens JJ, Aldenhoven M, Purtill D, Ruggeri A, Defor T, Wynn R, Wraith E, Cavazzana-Calvo M, Rovelli A, Fischer A, Tolar J, Prasad VK, Escolar M, Gluckman E, O'Meara A, Orchard PJ, Veys P, Eapen M, Kurtzberg J, Rocha V; Eurocord.; Inborn Errors Working Party of European Blood and Marrow Transplant group.; Duke University Blood and Marrow Transplantation Program.; Centre for International Blood and Marrow Research.
Blood 2013 May 9;121(19):3981-7. Epub 2013 Mar 14 doi: 10.1182/blood-2012-09-455238. PMID: 23493783Free PMC Article
Polgreen LE, Plog M, Schwender JD, Tolar J, Thomas W, Orchard PJ, Miller BS, Petryk A
Bone Marrow Transplant 2009 Sep;44(5):279-85. Epub 2009 Mar 2 doi: 10.1038/bmt.2009.31. PMID: 19252529Free PMC Article

Prognosis

Lukefahr AL, Proytcheva M
J Pediatr Hematol Oncol 2018 Jan;40(1):74-75. doi: 10.1097/MPH.0000000000001041. PMID: 29200150
Lum SH, Stepien KM, Ghosh A, Broomfield A, Church H, Mercer J, Jones S, Wynn R
J Inherit Metab Dis 2017 May;40(3):455-460. Epub 2017 Mar 10 doi: 10.1007/s10545-017-0034-6. PMID: 28283844
Kiely BT, Kohler JL, Coletti HY, Poe MD, Escolar ML
Orphanet J Rare Dis 2017 Feb 14;12(1):32. doi: 10.1186/s13023-017-0583-7. PMID: 28193245Free PMC Article
Yasin MN, Sacho R, Oxborrow NJ, Wraith JE, Williamson JB, Siddique I
Spine (Phila Pa 1976) 2014 Mar 1;39(5):381-7. doi: 10.1097/BRS.0000000000000157. PMID: 24573070
Braunlin E, Tolar J, Mackey-Bojack S, Masinde T, Krivit W, Schoen FJ
Cardiovasc Pathol 2011 Sep-Oct;20(5):315-21. Epub 2010 Jul 9 doi: 10.1016/j.carpath.2010.06.004. PMID: 20619689

Clinical prediction guides

Lum SH, Stepien KM, Ghosh A, Broomfield A, Church H, Mercer J, Jones S, Wynn R
J Inherit Metab Dis 2017 May;40(3):455-460. Epub 2017 Mar 10 doi: 10.1007/s10545-017-0034-6. PMID: 28283844
Kiely BT, Kohler JL, Coletti HY, Poe MD, Escolar ML
Orphanet J Rare Dis 2017 Feb 14;12(1):32. doi: 10.1186/s13023-017-0583-7. PMID: 28193245Free PMC Article
Schmidt M, Breyer S, Löbel U, Yarar S, Stücker R, Ullrich K, Müller I, Muschol N
Orphanet J Rare Dis 2016 Jul 8;11(1):93. doi: 10.1186/s13023-016-0470-7. PMID: 27392569Free PMC Article
Kennedy J, Noel J, O'Meara A, Mulhall K, Crushell E, Fogarty E, Kelly P
J Pediatr Orthop 2016 Jan;36(1):25-8. doi: 10.1097/BPO.0000000000000385. PMID: 26090987
Yasin MN, Sacho R, Oxborrow NJ, Wraith JE, Williamson JB, Siddique I
Spine (Phila Pa 1976) 2014 Mar 1;39(5):381-7. doi: 10.1097/BRS.0000000000000157. PMID: 24573070

Recent systematic reviews

Jameson E, Jones S, Remmington T
Cochrane Database Syst Rev 2016 Apr 1;4:CD009354. doi: 10.1002/14651858.CD009354.pub4. PMID: 27033167
Jameson E, Jones S, Wraith JE
Cochrane Database Syst Rev 2013 Nov 21;(11):CD009354. doi: 10.1002/14651858.CD009354.pub3. PMID: 24257962
Langereis EJ, Borgo A, Crushell E, Harmatz PR, van Hasselt PM, Jones SA, Kelly PM, Lampe C, van der Lee JH, Odent T, Sakkers R, Scarpa M, Schafroth MU, Struijs PA, Valayannopoulos V, White KK, Wijburg FA
Orphanet J Rare Dis 2013 Oct 3;8:155. doi: 10.1186/1750-1172-8-155. PMID: 24088413Free PMC Article
Jameson E, Jones S, Wraith JE
Cochrane Database Syst Rev 2013 Sep 26;(9):CD009354. doi: 10.1002/14651858.CD009354.pub2. PMID: 24085657

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