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Mucolipidosis Type 4

Mucolipidosis Type IV


Presentation

  • The presentation as a cerebral palsy-like encephalopathy may delay diagnosis.[ncbi.nlm.nih.gov]
  • Any fluorescent lipid present at the plasma membrane was then removed by back-exchange ( 6, 8 ).[doi.org]
  • Importantly, while MLIV is thought to be a rare disease, its frequency may be greater than currently appreciated, for its common presentation as a cerebral palsy-like encephalopathy can lead to misdiagnosis.[ncbi.nlm.nih.gov]
  • In the present study, we examined the hypothesis that the ML-IV phenotype might arise from abnormal transport along the lysosomal pathway.[ncbi.nlm.nih.gov]
  • This presentation of ML-IV is highly atypical taking into consideration the largest reported skin biopsy-proven series from India. [4] This cohort of 4 patients had a uniform presentation in adolescence with slowly progressive spastic paraparesis in stark[neurologyindia.com]
Microdontia
  • […] lower lip [ more ] 0000232 Genu recurvatum Back knee Knee hyperextension [ more ] 0002816 Microcephaly Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ] 0000252 Microdontia[rarediseases.info.nih.gov]
Corneal Opacity
  • It is a progressive disease that usually presents during the first year of life with mental retardation, corneal opacities, and delayed motor milestones.[ingentaconnect.com]
  • ., delayed development of movement and coordination), corneal opacity, retinal degeneration and other ophthalmological abnormalities.[en.wikipedia.org]
  • Treatment is based on the signs and symptoms present in each person. 0001344 Aplasia/Hypoplasia of the abdominal wall musculature Absent/small abdominal wall muscles Absent/underdeveloped abdominal wall muscles [ more ] 0010318 Corneal opacity 0007957[rarediseases.info.nih.gov]
  • Mucolipidosis IV (MLIV) is a progressive neurological lysosomal storage disease that usually is evident during the first year of life, and presents with mental retardation, corneal opacities, and delayed developmental milestones.[genedx.com]
Muscle Hypotonia
  • Infants with I-cell disease are typically underweight at birth, with muscle hypotonia and coarse facial features, the full clinical picture of the disorder presenting between 6 and 8 months. [5] Other features include joint stiffness, dislocated hips,[saudija.org]
Severe Osteoporosis
  • We were dealing with severe osteoporosis. "While in Sydney, we discussed with Professor Sillence at great length how we should treat this condition. Because of the level of Sarah's bone disease and pain we agreed to try a drug called Pamidronate.[nzord.org.nz]
Neck Pain
  • "In 1996 Hayden began suffering from unexplained neck pain, which was causing headaches and chronic tiredness. An MRI scan showed an area of the spinal cord was swollen and there was no spinal fluid protecting the cord.[nzord.org.nz]
Hyperreflexia
  • […] abdominal wall muscles Absent/underdeveloped abdominal wall muscles [ more ] 0010318 Corneal opacity 0007957 Developmental stagnation 0007281 Gait disturbance Abnormal gait Abnormal walk Impaired gait [ more ] 0001288 Ganglioside accumulation 0004345 Hyperreflexia[rarediseases.info.nih.gov]
  • Moreover, the trpv1 ( / ) mouse does not develop bladder overactivity during acute bladder inflammation, indicating that TRPV1 is involved in bladder hyperreflexia in inflammation ( 401 ). FIG. 12.[doi.org]
Babinski Sign
  • sign 0003487 Cerebellar atrophy Degeneration of cerebellum 0001272 Cerebral dysmyelination 0007266 Decreased light- and dark-adapted electroretinogram amplitude 0000654 Dysplastic corpus callosum 0006989 Dystonia 0001332 Generalized hypotonia Decreased[rarediseases.info.nih.gov]
Babinski Sign
  • sign 0003487 Cerebellar atrophy Degeneration of cerebellum 0001272 Cerebral dysmyelination 0007266 Decreased light- and dark-adapted electroretinogram amplitude 0000654 Dysplastic corpus callosum 0006989 Dystonia 0001332 Generalized hypotonia Decreased[rarediseases.info.nih.gov]

Workup

Generalized Sharp-and-Slow-Waves
  • Figure 1: Electroencephalogram (a) axial myoclonic jerks with characteristic burst of posterior predominant generalized sharp and slow wave followed by a period of attenuation of background activity, (b and c) interictal activity-profuse background slowing[neurologyindia.com]
Generalized Epileptiform Discharges
  • However, in some patients, slow but continuous improvements in cognitive, language and motor functions have been reported. [3] A constellation of psychomotor regression, multiple independent spike foci with generalized epileptiform discharges on EEG and[neurologyindia.com]
Gliosis
  • Slaugenhaupt, Behavioral deficits, early gliosis, dysmyelination and synaptic dysfunction in a mouse model of mucolipidosis IV, Acta Neuropathologica Communications, 2, 1, (2014).[doi.org]

Treatment

  • You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.[rarediseases.info.nih.gov]
  • . 5 months after treatment all other drugs for pain relief were removed. 6 months after treatment the first bone biopsy showed their first increase in bone density. 7 months after treatment their blood levels were within normal/high range. 11 months after[nzord.org.nz]
  • This review provides an update on the ethnic distribution, clinical manifestations, laboratory findings, methods of diagnosis, molecular genetics, differential diagnosis, and treatment of patients with MLIV.[ncbi.nlm.nih.gov]
  • treatment ( Table 1 ).[nature.com]

Prognosis

  • Because MLIV wasn’t recognized until 1974, little is known about prognosis and life expectancy beyond 30 years of age. Approximately 1 in 125 Ashkenazi Jews is a carrier of Mucolipidosis Type IV.[geneticdiseasefoundation.org]
  • Prognosis includes, shortened life span, reduced quality of life, and also additional complications with health 11.)Type of Genetic Inheritance Pattern: MLIV is an autosomal recessive pattern 12.)[spark.adobe.com]
  • The prognosis beyond this age, and the life expectancy of these patients is not known.[doi.org]
  • Melastatin expression and prognosis in cutaneous malignant melanoma. J Clin Oncol 19 : 568–576, 2001. Crossref PubMed ISI Google Scholar 108 Durvasula RV, Shankland SJ. Podocyte injury and targeting therapy: an update.[doi.org]

Etiology

  • Background: Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology. Patients develop corneal clouding, retinal degeneration, spastic quadriparesis, and mental retardation.[n.neurology.org]
  • The etiology of these disorders remains elusive, but evidence suggests a complex interplay of genetic and environmental factors ( 353 ).[doi.org]

Epidemiology

  • Relevant External Links for MCOLN1 Genetic Association Database (GAD) MCOLN1 Human Genome Epidemiology (HuGE) Navigator MCOLN1 Atlas of Genetics and Cytogenetics in Oncology and Haematology: MCOLN1 No data available for Genatlas for MCOLN1 Gene Mucolipidosis[genecards.org]
  • Epidemiology Frequency International Sialidosis is a rare disorder that has no racial predilection.[emedicine.medscape.com]
  • Exposure to air-borne particulate matter (PM) is epidemiologically associated with increased morbidity and mortality and is thought to initiate and exacerbate respiratory disorders such as asthma, cardiovascular complications, and allergy-related immune[doi.org]
Sex distribution
Age distribution

Pathophysiology

  • The physiological role of these complexes in lysosomal function remains to be elucidated, as well as their effect on the pathophysiology of MLIV.[biochemsoctrans.org]
  • (PMID: 16287144) Bach G … Ekstein J (Human mutation 2005) 3 22 45 60 Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel.[genecards.org]
  • Lysosomal multienzyme complex: biochemistry, genetics, and molecular pathophysiology. Prog Nucleic Acid Res Mol Biol . 2001. 69:81-114. [Medline] . Riches WG, Smuckler EA. A severe infantile mucolipidosis.[emedicine.medscape.com]
  • Lysosomal multienzyme complex: biochemistry, genetics, and molecular pathophysiology. Prog Nucleic Acid Res Mol Biol. 2001. 69:81-114. [Medline]. Riches WG, Smuckler EA. A severe infantile mucolipidosis.[emedicine.medscape.com]
  • Raychowdhury MK , Gonzalez-Perrett S , Montalbetti N , Timpanaro GA , Chasan B , Goldmann WH , Stahl S , Cooney A , Goldin E , Cantiello HF 2004 Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel .[nature.com]

Prevention

  • Most mutations in the MCOLN1 gene result in the production of a nonfunctional protein or prevent any protein from being produced.[checkorphan.org]
  • The demonstration of Fe 2 buildup in MLIV cells raised the possibility that TRPML1 dissipates lysosomal Fe 2 and prevents its accumulation.[biochemj.org]
  • Jenny explains: "Pamidronate is a synthetic compound that binds to bone to prevent absorption of bone by osteoclasts. Osteoclasts are bone cells, which break down bone tissue.[nzord.org.nz]
  • It was suggested that normally TRPML1 prevents overacidification in the lysosomes resulting from the catabolic activity, and thus, overacidification is caused by the malfunction of TRPML1 in MLIV.[nature.com]

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