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Ganglioside sialidase deficiency(ML4)

MedGen UID:
68663
Concept ID:
C0238286
Disease or Syndrome
Synonyms: Berman syndrome; Ganglioside neuraminidase deficiency; ML 4; ML IV; ML4; Mucolipidosis IV; Mucolipidosis type 4; Sialolipidosis; Type IV Mucolipidosis
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).
SNOMED CT: Mucolipidosis type IV (111384001); Ganglioside sialidase deficiency (111384001); Mucolipidosis IV (111384001)
 
Gene: MCOLN1
Cytogenetic location: 19p13.2
OMIM®: 252650
Orphanet: ORPHA578

Disease characteristics

Excerpted from the GeneReview: Mucolipidosis IV
Mucolipidosis IV is characterized by severe psychomotor delay evident by the end of the first year of life and slowly progressive visual impairment during the first decade as a result of a combination of corneal clouding and retinal degeneration. By the end of the first decade of life and certainly by their early teens, all individuals with typical mucolipidosis IV have severe visual impairment as a result of retinal degeneration. Neurodegeneration is thought to occur in no more than 15% of individuals. About 5% of individuals have atypical mucolipidosis IV, often manifest as less severe psychomotor retardation and/or eye findings. About 70% of individuals with mucolipidosis IV are of Ashkenazi Jewish heritage. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Raphael Schiffmann  |  Susan A Slaugenhaupt  |  Janine Smith, et. al.   view full author information

Additional descriptions

From OMIM
Mucolipidosis IV is an autosomal recessive neurodegenerative lysosomal storage disorder characterized by psychomotor retardation and ophthalmologic abnormalities. The lysosomal hydrolases in ML IV are normal, in contrast to most other storage diseases. The disorder results from a defect in transport along the lysosomal pathway, affecting membrane sorting and/or late steps of endocytosis, which causes intracellular accumulation of lysosomal substrates. Over 80% of the patients in whom the diagnosis of ML IV has been made are Ashkenazi Jews, including severely affected and mildly affected patients (Chen et al., 1998).  http://www.omim.org/entry/252650
From GHR
Mucolipidosis type IV is an inherited disorder characterized by delayed development and vision impairment that worsens over time. The severe form of the disorder is called typical mucolipidosis type IV, and the mild form is called atypical mucolipidosis type IV. Approximately 95 percent of individuals with this condition have the severe form. People with typical mucolipidosis type IV have delayed development of mental and motor skills (psychomotor delay). Motor skills include sitting, standing, walking, grasping objects, and writing. Psychomotor delay is moderate to severe and usually becomes apparent during the first year of life. Affected individuals have intellectual disability, limited or absent speech, difficulty chewing and swallowing, weak muscle tone (hypotonia) that gradually turns into abnormal muscle stiffness (spasticity), and problems controlling hand movements. Most people with typical mucolipidosis type IV are unable to walk independently. In about 15 percent of affected individuals, the psychomotor problems worsen over time. Vision may be normal at birth in people with typical mucolipidosis type IV, but it becomes increasingly impaired during the first decade of life. Individuals with this condition develop clouding of the clear covering of the eye (cornea) and progressive breakdown of the light-sensitive layer at the back of the eye (retina). By their early teens, affected individuals have severe vision loss or blindness. People with typical mucolipidosis type IV also have impaired production of stomach acid (achlorhydria). Achlorhydria does not cause any symptoms in these individuals, but it does result in unusually high levels of gastrin in the blood. Gastrin is a hormone that regulates the production of stomach acid. Individuals with mucolipidosis type IV may not have enough iron in their blood, which can lead to a shortage of red blood cells (anemia). People with the severe form of this disorder usually survive to adulthood; however, they may have a shortened lifespan. About 5 percent of affected individuals have atypical mucolipidosis type IV. These individuals usually have mild psychomotor delay and may develop the ability to walk. People with atypical mucolipidosis type IV tend to have milder eye abnormalities than those with the severe form of the disorder. Achlorhydria also may be present in mildly affected individuals.  http://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv

Clinical features

Narrow forehead
MedGen UID:
326408
Concept ID:
C1839127
Finding
Microcephaly
MedGen UID:
337454
Concept ID:
C1845868
Finding
Microdontia
MedGen UID:
342456
Concept ID:
C1850267
Finding
Coarse facial features
MedGen UID:
381459
Concept ID:
C1854600
Finding
Everted lower lip vermilion
MedGen UID:
504402
Concept ID:
CN000224
Finding
An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.
Abnormal nasal morphology
MedGen UID:
425310
Concept ID:
CN004530
Finding
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
Strabismus is the intermittent or constant misalignment of an eye so that its line of vision is not pointed at the same object as the other eye. Strabismus is caused by an imbalance in the extraocular muscles which control the positioning of the eyes. Strabismus is normal in newborns but should resolve by the time the baby is 6 months old. In older children with strabismus, the brain may learn to ignore the input from one eye, and this may lead to amblyopia, a potentially permanent decrease in vision in that eye if not corrected.
Abnormal electroretinogram
MedGen UID:
96908
Concept ID:
C0476397
Finding
Progressive retinal degeneration
MedGen UID:
343224
Concept ID:
C1854888
Finding
Opacification of the corneal stroma
MedGen UID:
347281
Concept ID:
C1856661
Finding
Abnormal retinal pigmentation
MedGen UID:
350681
Concept ID:
C1862475
Finding
Nystagmus
MedGen UID:
409575
Concept ID:
C1963184
Finding
Retinopathy
MedGen UID:
427824
Concept ID:
CN000456
Finding
Any noninflammatory disease of the retina. This nonspecific term is retained here because of its wide use in the literature, but if possible new annotations should indicate the precise type of retinal abnormality.
Photophobia
MedGen UID:
504524
Concept ID:
CN000575
Finding
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
Optic atrophy
MedGen UID:
504537
Concept ID:
CN000609
Finding
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Decreased electroretinogram (ERG) amplitude
MedGen UID:
500892
Concept ID:
CN000615
Finding
Descreased amplitude of eletrical response upon electroretinography.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
A reflex found in normal infants consisting of dorsiflexion of the HALLUX and abduction of the other TOES in response to cutaneous stimulation of the plantar surface of the FOOT. In adults, it is used as a diagnostic criterion, and if present is a NEUROLOGIC MANIFESTATION of dysfunction in the CENTRAL NERVOUS SYSTEM.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Sign or Symptom
A finding referring to walking difficulties.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Microcephaly
MedGen UID:
337454
Concept ID:
C1845868
Finding
Developmental stagnation
MedGen UID:
341348
Concept ID:
C1848980
Finding
Cognitive impairment
MedGen UID:
383844
Concept ID:
C1856145
Finding
Absent speech
MedGen UID:
383856
Concept ID:
C1856200
Finding
Incoordination
MedGen UID:
351047
Concept ID:
C1864113
Finding
Photophobia
MedGen UID:
504524
Concept ID:
CN000575
Finding
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
Cerebellar atrophy
MedGen UID:
504781
Concept ID:
CN001166
Finding
Atrophy (wasting) of the cerebellum.
Dystonia
MedGen UID:
504804
Concept ID:
CN001220
Finding
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Neurological speech impairment
MedGen UID:
446437
Concept ID:
CN001964
Finding
Spastic tetraplegia
MedGen UID:
505258
Concept ID:
CN002281
Finding
Spastic paralysis affecting all four limbs.
Dysplastic corpus callosum
MedGen UID:
777023
Concept ID:
CN006099
Finding
Dysplasia and dysgenesis of the corpus callosum are nonspecific descriptions that imply defective development of the corpus callosum. The term dysplasia is applied when the morphology of the corpus callosum is altered as a congenital trait. For instance, the corpus callosum may be hump-shaped, kinked, or a striped corpus callosum that lacks an anatomically distinct genu and splenium.
Cerebral dysmyelination
MedGen UID:
501026
Concept ID:
CN006355
Finding
Defective structure and function of myelin sheaths of the white matter of the brain.
Microcephaly
MedGen UID:
337454
Concept ID:
C1845868
Finding
Genu recurvatum
MedGen UID:
505362
Concept ID:
CN002543
Finding
An abnormally increased extension of the knee joint, so that the knee can bend backwards.
Abnormality of the abdomen
MedGen UID:
425046
Concept ID:
CN001314
Finding
Abnormality of the abdomen ('belly'), that is, the part of the body between the pelvis and the thorax.
Aplasia/Hypoplasia of the abdominal wall musculature
MedGen UID:
447243
Concept ID:
CN009150
Finding
Absence or underdevelopment of the abdominal musculature.
Palmoplantar keratoderma
MedGen UID:
400147
Concept ID:
C1862859
Finding
Abnormality of ganglioside metabolism
MedGen UID:
428453
Concept ID:
CN003846
Finding
Abnormality of ganglioside metabolism.
Abnormality of mucopolysaccharide metabolism
MedGen UID:
451291
Concept ID:
CN116752
Finding
An abnormality of the metabolism of mucopolysaccharide.
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Spastic tetraplegia
MedGen UID:
505258
Concept ID:
CN002281
Finding
Spastic paralysis affecting all four limbs.
Genu recurvatum
MedGen UID:
505362
Concept ID:
CN002543
Finding
An abnormally increased extension of the knee joint, so that the knee can bend backwards.

Professional guidelines

PubMed

ACOG Committee on Genetics
Obstet Gynecol 2009 Oct;114(4):950-3. doi: 10.1097/AOG.0b013e3181bd12f4. PMID: 19888064
Gross SJ, Pletcher BA, Monaghan KG; Professional Practice and Guidelines Committee
Genet Med 2008 Jan;10(1):54-6. doi: 10.1097/GIM.0b013e31815f247c. PMID: 18197057Free PMC Article

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