MUCOLIPIDOSIS III ALPHA/BETA

General Information (adopted from Orphanet):

Synonyms, Signs: MUCOLIPIDOSIS III
ML IIIA
PSEUDO-HURLER POLYDYSTROPHY MUCOLIPIDOSIS III ALPHA/BETA, ATYPICAL, INCLUDED
MUCOLIPIDOSIS IIIA
ML III
ML III ALPHA/BETA
Number of Symptoms 33
OrphanetNr:
OMIM Id: 252600
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive inheritance
[Omim]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: No data available.

Symptom Information: Sort by abundance 

1
(HPO:0002680) J-shaped sella turcica 15 / 7739
2
(HPO:0000303) Mandibular prognathia 179 / 7739
3
(HPO:0001363) Craniosynostosis 132 / 7739
4
(HPO:0007957) Corneal opacity 84 / 7739
5
(HPO:0000484) Hyperopic astigmatism 8 / 7739
6
(HPO:0001328) Specific learning disability 114 / 7739
7
(HPO:0001249) Intellectual disability 1089 / 7739
8
(HPO:0003026) Short long bone 51 / 7739
9
(HPO:0000943) Dysostosis multiplex 22 / 7739
10
(HPO:0006162) Soft tissue swelling of interphalangeal joints 2 / 7739
11
(HPO:0002650) Scoliosis 705 / 7739
12
(HPO:0003182) Shallow acetabular fossae 10 / 7739
13
(HPO:0001171) Split hand 72 / 7739
14
(HPO:0004322) Short stature 1232 / 7739
15
(HPO:0001072) Thickened skin 87 / 7739
16
(HPO:0001659) Aortic regurgitation 36 / 7739
17
(HPO:0003264) Deficiency of N-acetylglucosamine-1-phosphotransferase 3 / 7739
18
(HPO:0003538) Increased serum iduronate sulfatase activity 4 / 7739
19
(HPO:0003333) Increased serum beta-hexosaminidase 4 / 7739
20
(OMIM) Vertebral beaking 1 / 7739
21
(OMIM) Flaring of iliac wings 2 / 7739
22
(OMIM) Mildly coarse facies 2 / 7739
23
(OMIM) No mucopolysacchariduria 4 / 7739
24
(OMIM) Small, irregular carpal bones 1 / 7739
25
(OMIM) Wide, slightly short ribs 1 / 7739
26
(OMIM) Shoulder stiffness 2 / 7739
27
(OMIM) Increased serum aryl-sulfatase A (10-20x) 1 / 7739
28
(OMIM) Mild retinopathy 1 / 7739
29
(MedDRA:10007697) Carpal tunnel syndrome 16 / 7739
30
(OMIM) Broad metaphyses 2 / 7739
31
(OMIM) Hand stiffness 2 / 7739
32
(OMIM) Absence of dens 1 / 7739
33
(OMIM) Short, thick clavicles 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Mucolipidosis type III alpha/beta is an autosomal recessive disorder characterized clinically by short stature, skeletal abnormalities, cardiomegaly, and developmental delay. The disorder is caused by a defect in proper lysosomal enzyme phosphorylation and localization, which results in accumulation ...
Clinical Description OMIM Under the designation 'pseudo-polydystrophie de Hurler,' Maroteaux and Lamy (1966) described 4 cases with many of the features of the Hurler syndrome but a much slower clinical evolution and no mucopolysacchariduria. The bone marrow contained cells reminiscent of ...
Genotype-Phenotype Correlations OMIM Otomo et al. (2009) identified 18 GNPTAB mutations, including 14 novel mutations, among 25 unrelated Japanese patients with ML II and 15 Japanese patients with ML III. The most common mutations were R1189X (607840.0004), which was found in ...
Molecular genetics OMIM Canfield et al. (1998) found that in 2 of 2 patients with mucolipidosis IIIA, the GlcNAc-phosphotransferase alpha/beta transcript (GNPTAB; 607840) was present but greatly reduced. In 4 of 4 patients with mucolipidosis II, the GNPTAB transcript was absent. ...
Diagnosis GeneReviews The following clinical features contribute to early diagnosis of mucolipidosis III alpha/beta (ML III alpha/beta) [Cathey et al 2010] but are not by themselves diagnostic:...
Clinical Description GeneReviews Mucolipidosis III alpha/beta (ML III alpha/beta; pseudo-Hurler polydystrophy) is a slowly progressive inborn error of metabolism with clinical onset at approximately age three years and fatal outcome in early to middle adulthood [Leroy 2007, Cathey et al 2010]. Comprehensive data on life expectancy are still lacking....
Genotype-Phenotype Correlations GeneReviews GNPTAB sequencing has been available only since 2005; however, the overall results of several studies have confirmed that homozygous and compound heterozygous genotypes that produce no or nearly no functional GlcNAc-1-phosphotransferase activity (caused by premature translation termination and/or frameshift effects) result in the ML II phenotype. The combination of less “morbid” mutations (e.g., missense and most of the splice-site mutations that result in up to 10% of residual GlcNAc-1-phosphotransferase activity) often yield the more slowly evolving ML III alpha/beta phenotype [Tiede et al 2005, Paik et al 2005, Bargal et al 2006, Kudo et al 2006, Encarnaçao et al 2009, Otomo et al 2009, Tappino et al 2009, Cathey et al 2010, David-Vizcarra et al 2010, Cury et al 2011]....
Differential Diagnosis GeneReviews Mucolipidosis III gamma. The clinical features of mucolipidosis III gamma (also known as variant ML III) are similar to but milder than those observed in individuals with mucolipidosis III alpha/beta (ML III alpha/beta). In most of the published case reports of ML III gamma, affected individuals are of Middle Eastern descent [Raas-Rothschild et al 2000, Raas-Rothschild et al 2004, Cathey et al 2008]. If the diagnosis of ML III is strongly suspected clinically and molecular analysis of GNPTAB does not reveal disease-causing mutations, analysis of GNPTG should be performed....
Management GeneReviews To establish the extent of disease in an individual diagnosed with mucolipidosis III alpha/beta (ML III alpha/beta), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....