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I cell disease

MedGen UID:
435914
Concept ID:
C2673377
Disease or Syndrome
Synonyms: GNPTAB-Related Mucolipidoses; I-cell disease; Inclusion cell disease; Leroy Disease; ML 2; ML disorder type 2; ML II ALPHA/BETA; Mucolipidosis 2; Mucolipidosis II; Mucolipidosis III Alpha/Beta; N-acetylglucosamine 1phosphotransferase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
 
Gene: GNPTAB
Cytogenetic location: 12q23.2
OMIM®: 252500
Orphanet: ORPHA576

Disease characteristics

Excerpted from the GeneReview: Mucolipidosis II
Mucolipidosis II (ML II, I-cell disease) is a slowly progressive inborn error of metabolism with clinical onset at birth and fatal outcome most often in early childhood. Postnatal growth is limited and often ceases in the second year of life; contractures develop in all large joints. The skin is thickened, facial features are coarse, and gingiva are hypertrophic. Orthopedic abnormalities present at birth may include thoracic deformity, kyphosis, clubfeet, deformed long bones, and/or dislocation of the hip(s). Already in infancy skeletal radiographs reveal dysostosis multiplex. All children appear to have cardiac involvement, most commonly thickening and insufficiency of the mitral valve and, less frequently, the aortic valve. Progressive mucosal thickening narrows the airways and gradual stiffening of the thoracic cage contributes to respiratory insufficiency, the most common cause of death. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Jules G Leroy  |  Sara Cathey  |  Michael J Friez   view full author information

Additional descriptions

From OMIM
Mucolipidosis type II 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 of lysosomal substrates. It is phenotypically more severe than the allelic disorder mucolipidosis type III alpha/beta (summary by Paik et al., 2005).  http://www.omim.org/entry/252500
From GHR
Mucolipidosis II alpha/beta (also known as I-cell disease) is a progressively debilitating disorder that affects many parts of the body. Most affected individuals do not survive past early childhood. At birth, children with mucolipidosis II alpha/beta are small and have weak muscle tone (hypotonia) and a weak cry. Affected individuals grow slowly after birth and usually stop growing during the second year of life. Development is delayed, particularly the development of speech and motor skills such as sitting and standing. Children with mucolipidosis II alpha/beta typically have several bone abnormalities, many of which are present at birth. Affected individuals may have an abnormally rounded upper back (kyphosis), feet that are abnormally rotated (clubfeet), dislocated hips, unusually shaped long bones, and short hands and fingers. People with this condition also have joint deformities (contractures) that significantly affect mobility. Most children with mucolipidosis II alpha/beta do not develop the ability to walk independently. Affected individuals have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Other features of mucolipidosis II alpha/beta include a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia), heart valve abnormalities, distinctive-looking facial features that are described as "coarse," and overgrowth of the gums (gingival hypertrophy). Vocal cords can stiffen, resulting in a hoarse voice. The airway is narrow, which can contribute to prolonged or recurrent respiratory infections. Affected individuals may also have recurrent ear infections, which can lead to hearing loss.  http://ghr.nlm.nih.gov/condition/mucolipidosis-ii-alpha-beta

Clinical features

Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Sign or Symptom
Slower than normal rate of weight increase.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Weight loss
MedGen UID:
504965
Concept ID:
CN001653
Finding
Reduction inexisting body weight.
Severe postnatal growth retardation
MedGen UID:
501055
Concept ID:
CN007785
Finding
Severely slow or limited growth after birth, being four standard deviations or more below age- and sex-related norms.
Cavernous hemangioma
MedGen UID:
504697
Concept ID:
CN000983
Finding
The presence of a cavernous hemangioma. A hemangioma characterized by large endothelial spaces (caverns) is called a cavernous hemangioma.
Mucopolysacchariduria
MedGen UID:
425962
Concept ID:
CN007161
Finding
Excessive amounts of mucopolysaccharide in the urine.
Palpebral edema
MedGen UID:
57877
Concept ID:
C0162285
Finding
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
Epicanthus
MedGen UID:
724513
Concept ID:
C1303004
Finding
Narrow forehead
MedGen UID:
326408
Concept ID:
C1839127
Finding
Large sella turcica
MedGen UID:
334811
Concept ID:
C1843677
Finding
Anteverted nares
MedGen UID:
339940
Concept ID:
C1853244
Finding
Coarse facial features
MedGen UID:
381459
Concept ID:
C1854600
Finding
Progressive alveolar ridge hypertropy
MedGen UID:
340753
Concept ID:
C1854934
Finding
Thickened calvaria
MedGen UID:
347516
Concept ID:
C1857647
Finding
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Macroglossia
MedGen UID:
504371
Concept ID:
CN000154
Finding
Increased length and width of the tongue.
Broad alveolar ridges
MedGen UID:
500884
Concept ID:
CN000182
Finding
Sparse eyebrow
MedGen UID:
500888
Concept ID:
CN000501
Finding
Decreased density/number and/or decreased diameter of eyebrow hairs.
Recurrent bronchitis
MedGen UID:
505369
Concept ID:
CN002562
Finding
An increased susceptibility to bronchitis as manifested by a history of recurrent bronchitis.
Depressed nasal bridge
MedGen UID:
446656
Concept ID:
CN004681
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Opacification of the corneal stroma
MedGen UID:
347281
Concept ID:
C1856661
Finding
Megalocornea
MedGen UID:
504461
Concept ID:
CN000453
Finding
An enlargement of the cornea with normal clarity and function. Megalocornea is diagnosed with a horizontal corneal diameter of 12 mm or more at birth or 13 mm or more after two years of age.
Corneal dystrophy
MedGen UID:
504738
Concept ID:
CN001063
Finding
An abnormality of the cornea that is characterized by opacity of one or parts of the cornea.
Corneal erosion
MedGen UID:
506552
Concept ID:
CN117761
Finding
An erosion or abrasion of the cornea's outermost layer of epithelial cells.
Recurrent otitis media
MedGen UID:
332967
Concept ID:
C1837887
Finding
Cognitive impairment
MedGen UID:
383844
Concept ID:
C1856145
Finding
Morphological abnormality of the central nervous system
MedGen UID:
428288
Concept ID:
CN001820
Finding
A structural abnormality of the central nervous system.
Myelopathy
MedGen UID:
505152
Concept ID:
CN001991
Finding
Severe global developmental delay
MedGen UID:
506566
Concept ID:
CN167072
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Wide intermamillary distance
MedGen UID:
428638
Concept ID:
CN005758
Finding
A larger than usual distance between the left and right nipple.
Ovoid vertebral bodies
MedGen UID:
373195
Concept ID:
C1836864
Finding
Flat acetabular roof
MedGen UID:
373340
Concept ID:
C1837485
Finding
Large sella turcica
MedGen UID:
334811
Concept ID:
C1843677
Finding
Kyphosis
MedGen UID:
335104
Concept ID:
C1845112
Finding
Lower thoracic interpediculate narrowness
MedGen UID:
343232
Concept ID:
C1854940
Finding
Beaking of vertebral bodies T12-L3
MedGen UID:
381522
Concept ID:
C1854941
Finding
Varus deformity of humeral neck
MedGen UID:
340755
Concept ID:
C1854948
Finding
Bullet-shaped phalanges of the hand
MedGen UID:
344396
Concept ID:
C1854952
Finding
Metaphyseal widening
MedGen UID:
344455
Concept ID:
C1855248
Finding
A radiologic finding characterized by an increased width of the metaphyseal regions. It is seen in rickets.
Thickened calvaria
MedGen UID:
347516
Concept ID:
C1857647
Finding
Thoracolumbar kyphoscoliosis
MedGen UID:
347124
Concept ID:
C1859335
Finding
Flared iliac wings
MedGen UID:
356097
Concept ID:
C1865841
Finding
Carpal bone hypoplasia
MedGen UID:
361803
Concept ID:
C1873508
Finding
Osteopenia
MedGen UID:
409692
Concept ID:
C1968854
Finding
Abnormality of the thorax
MedGen UID:
427834
Concept ID:
CN000719
Finding
Any abnormality of the thorax (the region of the body formed by the sternum, the thoracic vertebrae and the ribs).
Hypoplastic scapulae
MedGen UID:
504641
Concept ID:
CN000827
Finding
Underdeveloped scapula.
Split hand
MedGen UID:
504754
Concept ID:
CN001098
Finding
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middel fingers as far as oligo- or monodactyl hands.
Abnormality of the rib cage
MedGen UID:
428272
Concept ID:
CN001412
Finding
A morphological anomaly of the rib cage.
Pathologic fracture
MedGen UID:
505347
Concept ID:
CN002501
Finding
A pathologic fracture occurs when a bone breaks in an area that is weakened secondary to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Hip dislocation
MedGen UID:
505364
Concept ID:
CN002553
Finding
Displacement of the femur from its normal location in the hip joint.
Abnormality of the wrist
MedGen UID:
446466
Concept ID:
CN002729
Finding
Abnormality of the wrist, the structure connecting the hand and the forearm.
Short long bone
MedGen UID:
832972
Concept ID:
CN002735
Finding
One or more abnormally short long bone.
Hypoplasia of the odontoid process
MedGen UID:
500949
Concept ID:
CN002987
Finding
Developmental hypoplasia of the dens of the axis.
Atlantoaxial dislocation
MedGen UID:
505533
Concept ID:
CN003080
Finding
Partial dislocation of the atlantoaxial joint.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Protuberant abdomen
MedGen UID:
336535
Concept ID:
C1849208
Finding
Inguinal hernia
MedGen UID:
504305
Concept ID:
CN000024
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Diastasis recti
MedGen UID:
504851
Concept ID:
CN001406
Finding
A separation of the rectus abdominis muscle into right and left halves (which are normally joined at the midline at the linea alba).
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Thin skin
MedGen UID:
140848
Concept ID:
C0423757
Finding
Lack of skin elasticity
MedGen UID:
107840
Concept ID:
C0558242
Finding
Sparse eyebrow
MedGen UID:
500888
Concept ID:
CN000501
Finding
Decreased density/number and/or decreased diameter of eyebrow hairs.
Hypertrichosis
MedGen UID:
504680
Concept ID:
CN000934
Finding
Hypertrichosis is increased hair growth that is abnormal in quantity or location.
Cavernous hemangioma
MedGen UID:
504697
Concept ID:
CN000983
Finding
The presence of a cavernous hemangioma. A hemangioma characterized by large endothelial spaces (caverns) is called a cavernous hemangioma.
Hoarse voice
MedGen UID:
504872
Concept ID:
CN001465
Finding
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
hypertrophy or enlargement of the heart.
Heart murmur
MedGen UID:
9171
Concept ID:
C0018808
Finding
A periodic humming or blowing sound heard on auscultation of the heart that can indicate the presence of cardiac disease; murmurs are the result of vibrations caused by the turbulent flow of blood in the heart or great vessels. Murmurs are characterized according to the area of generation (mitral, aortic, tricuspid, or pulmonary) and according to the period of the cycle (systolic or diastolic).
Cavernous hemangioma
MedGen UID:
504697
Concept ID:
CN000983
Finding
The presence of a cavernous hemangioma. A hemangioma characterized by large endothelial spaces (caverns) is called a cavernous hemangioma.
Congestive heart failure
MedGen UID:
504881
Concept ID:
CN001488
Finding
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Hypertrophic cardiomyopathy
MedGen UID:
504884
Concept ID:
CN001492
Finding
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Abnormality of the heart valves
MedGen UID:
446421
Concept ID:
CN001506
Finding
An abnormality of a Cardiac valve.
Aortic regurgitation
MedGen UID:
504897
Concept ID:
CN001510
Finding
An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle.
Palpebral edema
MedGen UID:
57877
Concept ID:
C0162285
Finding
Increased serum iduronate sulfatase activity
MedGen UID:
340747
Concept ID:
C1854916
Finding
Increased serum beta-hexosaminidase
MedGen UID:
435911
Concept ID:
C2673361
Finding
Deficiency of N-acetylglucosamine-1-phosphotransferase
MedGen UID:
505502
Concept ID:
CN002947
Finding
Mucopolysacchariduria
MedGen UID:
425962
Concept ID:
CN007161
Finding
Excessive amounts of mucopolysaccharide in the urine.
Recurrent respiratory infections
MedGen UID:
400943
Concept ID:
C1866203
Finding
Recurrent bronchitis
MedGen UID:
505369
Concept ID:
CN002562
Finding
An increased susceptibility to bronchitis as manifested by a history of recurrent bronchitis.
Recurrent pneumonia
MedGen UID:
505924
Concept ID:
CN005690
Finding
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Recurrent otitis media
MedGen UID:
332967
Concept ID:
C1837887
Finding
Recurrent respiratory infections
MedGen UID:
400943
Concept ID:
C1866203
Finding
Recurrent bronchitis
MedGen UID:
505369
Concept ID:
CN002562
Finding
An increased susceptibility to bronchitis as manifested by a history of recurrent bronchitis.
Recurrent pneumonia
MedGen UID:
505924
Concept ID:
CN005690
Finding
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Neonatal hypotonia
MedGen UID:
331807
Concept ID:
C1834679
Finding
Macroglossia
MedGen UID:
504371
Concept ID:
CN000154
Finding
Increased length and width of the tongue.
Diastasis recti
MedGen UID:
504851
Concept ID:
CN001406
Finding
A separation of the rectus abdominis muscle into right and left halves (which are normally joined at the midline at the linea alba).
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Inguinal hernia
MedGen UID:
504305
Concept ID:
CN000024
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Hernia
MedGen UID:
452018
Concept ID:
CN117680
Finding
Flat acetabular roof
MedGen UID:
373340
Concept ID:
C1837485
Finding
Talipes equinovarus
MedGen UID:
335852
Concept ID:
C1842988
Finding
Varus deformity of humeral neck
MedGen UID:
340755
Concept ID:
C1854948
Finding
Bullet-shaped phalanges of the hand
MedGen UID:
344396
Concept ID:
C1854952
Finding
Metaphyseal widening
MedGen UID:
344455
Concept ID:
C1855248
Finding
A radiologic finding characterized by an increased width of the metaphyseal regions. It is seen in rickets.
Carpal bone hypoplasia
MedGen UID:
361803
Concept ID:
C1873508
Finding
Split hand
MedGen UID:
504754
Concept ID:
CN001098
Finding
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middel fingers as far as oligo- or monodactyl hands.
Hip dislocation
MedGen UID:
505364
Concept ID:
CN002553
Finding
Displacement of the femur from its normal location in the hip joint.
Abnormality of the wrist
MedGen UID:
446466
Concept ID:
CN002729
Finding
Abnormality of the wrist, the structure connecting the hand and the forearm.

Recent clinical studies

Etiology

Lin MH, Pitukcheewanont P
J Pediatr Endocrinol Metab 2012;25(1-2):191-5. doi: 10.1515/jpem-2011-0429. PMID: 22570975
Yuksel A, Kayserili H, Gungor F
Fetal Diagn Ther 2007;22(3):198-202. Epub 2007 Jan 17 doi: 10.1159/000098717. [Epub ahead of print] PMID: 17228159
Breningstall GN, Tubman DE
Clin Neurol Neurosurg 1994 May;96(2):161-3. PMID: 7924082
Reitman ML, Varki A, Kornfeld S
J Clin Invest 1981 May;67(5):1574-9. PMID: 6262380Free PMC Article
Owada M, Nishiya O, Sakiyama T, Kitagawa T
J Inherit Metab Dis 1980;3(4):117-21. PMID: 6787332

Diagnosis

Lin MH, Pitukcheewanont P
J Pediatr Endocrinol Metab 2012;25(1-2):191-5. doi: 10.1515/jpem-2011-0429. PMID: 22570975
Takanashi J, Hayashi M, Yuasa S, Satoh H, Terada H
Brain Dev 2012 Oct;34(9):780-3. Epub 2012 Jan 24 doi: 10.1016/j.braindev.2011.12.013. [Epub ahead of print] PMID: 22269149
Chang SH, Lin SJ, Lee YY, Yang RC, Yang SL
Kaohsiung J Med Sci 1996 May;12(5):295-300. PMID: 8676436
Hwu WL, Chuang SC, Wang WC, Wang TR
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1994 Nov-Dec;35(6):508-13. PMID: 7831983
Owada M, Nishiya O, Sakiyama T, Kitagawa T
J Inherit Metab Dis 1980;3(4):117-21. PMID: 6787332

Therapy

Lee W, O'Donnell D
Int J Paediatr Dent 2003 Jan;13(1):41-5. PMID: 12542623
Hochman JA, Treem WR, Dougherty F, Bentley RC
J Inherit Metab Dis 2001 Oct;24(5):603-4. PMID: 11757590
Ylikangas PK, Mononen IT
Clin Chem 1998 Dec;44(12):2543-4. PMID: 9882166
Tylki-Szymańska A, Maciejko D, Kidawa M, Jabłońska-Budaj U, Czartoryska B
J Inherit Metab Dis 1985;8(3):101-4. PMID: 3939584
van Dongen JM, Willemsen R, Ginns EI, Sips HJ, Tager JM, Barranger JA, Reuser AJ
Eur J Cell Biol 1985 Nov;39(1):179-89. PMID: 2935398

Prognosis

Saul RA, Proud V, Taylor HA, Leroy JG, Spranger J
Am J Med Genet A 2005 Jun 15;135(3):328-32. doi: 10.1002/ajmg.a.30716. PMID: 15887289
Kabra M, Gulati S, Kaur M, Sharma J, Singh A, Chopra V, Menon PS, Kalra V
Indian J Pediatr 2000 Sep;67(9):683-7. PMID: 11028124
Güngör N, Coşkun T, Akçören Z, Cağlar M
Turk J Pediatr 1994 Apr-Jun;36(2):145-52. PMID: 8016916
Breningstall GN, Tubman DE
Clin Neurol Neurosurg 1994 May;96(2):161-3. PMID: 7924082
Matsuda I, Arashima S, Mitsuyama T, Oka Y, Ikeuchi T, Kaneko Y, Ishikawa M
Humangenetik 1975 Oct 20;30(1):69-73. PMID: 171215

Clinical prediction guides

Sheikh S, Madiraju K, Qazi Q, Rao M
Pediatr Pulmonol 1998 Feb;25(2):128-9. PMID: 9516097
Chang SH, Lin SJ, Lee YY, Yang RC, Yang SL
Kaohsiung J Med Sci 1996 May;12(5):295-300. PMID: 8676436
Reitman ML, Varki A, Kornfeld S
J Clin Invest 1981 May;67(5):1574-9. PMID: 6262380Free PMC Article
Owada M, Nishiya O, Sakiyama T, Kitagawa T
J Inherit Metab Dis 1980;3(4):117-21. PMID: 6787332
Vladutiu GD, Rattazzi MC
J Clin Invest 1979 Apr;63(4):595-601. doi: 10.1172/JCI109341. PMID: 438323Free PMC Article

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