MUCOLIPIDOSIS III GAMMA

General Information (adopted from Orphanet):

Synonyms, Signs: MUCOLIPIDOSIS III, IRANIAN VARIANT FORM
ML IIIC
MUCOLIPIDOSIS IIIC
MUCOLIPIDOSIS III, VARIANT FORM
MUCOLIPIDOSIS III, COMPLEMENTATION GROUP C
ML III GAMMA
Number of Symptoms 39
OrphanetNr:
OMIM Id: 252605
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:0000280) Coarse facial features 189 / 7739
2
(HPO:0000470) Short neck 345 / 7739
3
(HPO:0007759) Opacification of the corneal stroma 77 / 7739
4
(HPO:0000545) Myopia 286 / 7739
5
(HPO:0001256) Intellectual disability, mild 141 / 7739
6
(HPO:0001171) Split hand 72 / 7739
7
(HPO:0001547) Abnormality of the rib cage 25 / 7739
8
(HPO:0001387) Joint stiffness 322 / 7739
9
(HPO:0000768) Pectus carinatum 136 / 7739
10
(HPO:0000943) Dysostosis multiplex 22 / 7739
11
(HPO:0003370) Flat capital femoral epiphysis 15 / 7739
12
(HPO:0002808) Kyphosis 289 / 7739
13
(HPO:0002869) Flared iliac wings 20 / 7739
14
(HPO:0002857) Genu valgum 144 / 7739
15
(HPO:0003307) Hyperlordosis 122 / 7739
16
(HPO:0002829) Arthralgia 79 / 7739
17
(HPO:0001155) Abnormality of the hand 54 / 7739
18
(HPO:0002650) Scoliosis 705 / 7739
19
(HPO:0004322) Short stature 1232 / 7739
20
(HPO:0001650) Aortic valve stenosis 49 / 7739
21
(HPO:0001659) Aortic regurgitation 36 / 7739
22
(HPO:0003538) Increased serum iduronate sulfatase activity 4 / 7739
23
(HPO:0003333) Increased serum beta-hexosaminidase 4 / 7739
24
(OMIM) Decreased fibroblast alpha-mannosidase 1 / 7739
25
(OMIM) Increased serum alpha-mannosidase 1 / 7739
26
(OMIM) Decreased fibroblast arylsulfatase A 1 / 7739
27
(OMIM) Thoracic asymmetry 2 / 7739
28
(OMIM) Increased serum arylsulfatase A (10-20x) 2 / 7739
29
(OMIM) Joint stiffness, progressive 2 / 7739
30
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739
31
(OMIM) Aortic valve thickening 3 / 7739
32
(OMIM) Decreased N-acetylglucosamine-1-phosphotransferase (GlcNAc - phosphotransferase) using lysosomal enzymes 1 / 7739
33
(OMIM) Fine corneal opacities 1 / 7739
34
(OMIM) Normal-to-slightly decreased GlcNAc phosphotransferase using artificial substrate (e.g., alpha-methylmannoside) 1 / 7739
35
(OMIM) No mucopolysacchariduria 4 / 7739
36
(OMIM) Decreased fibroblast iduronate sulfatase 1 / 7739
37
(OMIM) Shoulder stiffness 2 / 7739
38
(OMIM) Hand stiffness 2 / 7739
39
(OMIM) Decreased fibroblast beta-hexosaminidase 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Mucolipidosis type III gamma 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 Encarnacao et al. (2009) reported a Portuguese patient with mucolipidosis III gamma. He had a relatively mild phenotype with onset at age 10 years, no psychomotor retardation, and survival into adulthood.

Pohl et al. (2010) reported ...

Molecular genetics OMIM By sequence analysis, Raas-Rothschild et al. (2000) identified a frameshift mutation in the GNPTG gene (607838.0001) in affected members of 3 families with ML IIIC. Raas-Rothschild et al. (2000) suggested that the gamma subunit functions in lysosomal hydrolase ...
Diagnosis GeneReviews The following clinical features, similar to those for mucolipidosis III alpha/beta, contribute to early diagnosis of mucolipidosis III gamma (ML III gamma) but are not by themselves diagnostic [Raas-Rothschild et al 2004, Cathey et al 2009]:...
Clinical Description GeneReviews Mucolipidosis III is a slowly progressive inborn error of metabolism mainly affecting skeletal, joint, and connective tissues. Clinical onset is in early childhood and the progressive course, including cardiac involvement, results in severe functional impairment and significant morbidity. A few affected individuals may display mild cognitive impairment [Leroy 2007]; but the majority do not....
Genotype-Phenotype Correlations GeneReviews To date no correlation between severity of disease and type of mutation has been reported....
Differential Diagnosis GeneReviews Mucolipidosis II (ML II) alpha/beta, ML III alpha/beta, and ML III gamma are all UPDGlcNAc 1-P-transferase deficiency disorders (see Nomenclature). Whereas the clinical phenotypes of ML III alpha/beta and ML III gamma can be difficult to distinguish, the severe ML II (I-cell disease) phenotype is easily differentiated....
Management GeneReviews To establish the extent of disease in an individual diagnosed with ML III gamma, 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....