Oculocerebrorenal syndrome: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{CMG}}; {{AE}} {{AN}} | |||
{{SK}} Lowe's syndrome | |||
{{Infobox_Disease | | {{Infobox_Disease | | ||
Name = {{PAGENAME}} | | Name = {{PAGENAME}} | | ||
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MeshID = D009800 | | MeshID = D009800 | | ||
}} | }} | ||
==Overview== | ==Overview== | ||
'''Oculocerebrorenal syndrome''' is a [[X-linked]] recessive disorder characterized by [[hydrophthalmia]], [[cataract]]s, [[mental retardation]], [[aminoaciduria]], reduced renal [[ammonia]] production and vitamin D-resistant [[rickets]]. | '''Oculocerebrorenal syndrome''' is a [[X-linked]] recessive disorder characterized by [[hydrophthalmia]], [[cataract]]s, [[mental retardation]], [[aminoaciduria]], reduced renal [[ammonia]] production and vitamin D-resistant [[rickets]]. | ||
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==Historical Perspective== | ==Historical Perspective== | ||
It is named after Charles Upton Lowe, who was the first to describe the condition.<ref>{{WhoNamedIt|synd|3512}}</ref><ref>{{cite journal |author=Lowe CU, Terrey M, MacLachlan EA |title=Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity |journal=A.M.A. American journal of diseases of children |volume=83 |issue=2 |pages=164-84 |year=1952 |pmid=14884753 |doi=}}</ref> | It is named after Charles Upton Lowe, who was the first to describe the condition.<ref>{{WhoNamedIt|synd|3512}}</ref><ref>{{cite journal |author=Lowe CU, Terrey M, MacLachlan EA |title=Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity |journal=A.M.A. American journal of diseases of children |volume=83 |issue=2 |pages=164-84 |year=1952 |pmid=14884753 |doi=}}</ref> | ||
==Classification== | |||
==Pathophysiology== | ==Pathophysiology== | ||
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===Genetics=== | ===Genetics=== | ||
It is associated with [[mutation]] in the [[gene]] [[OCRL]]. | It is associated with [[mutation]] in the [[gene]] [[OCRL]]. | ||
==Causes== | |||
==Differentiating Oculocerebrorenal syndrome from other diseases== | ==Differentiating Oculocerebrorenal syndrome from other diseases== | ||
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*As the disease follows an [[X-linked]] inheritance pattern, almost all affected patients are males. However, a few females with this condition have been reported. | *As the disease follows an [[X-linked]] inheritance pattern, almost all affected patients are males. However, a few females with this condition have been reported. | ||
==Complications== | ==Risk Factors== | ||
==Screening== | |||
==Natural History, Complications, and Prognosis== | |||
*[[Muscle tone]] improves with age, but never comes back to normal. | *[[Muscle tone]] improves with age, but never comes back to normal. | ||
*[[Scoliosis]] | *[[Scoliosis]] | ||
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==Diagnosis== | ==Diagnosis== | ||
===History=== | ===History and Symptoms=== | ||
*[[Mental retardation]] | *[[Mental retardation]] | ||
*[[Seizures]] | *[[Seizures]] | ||
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*[[Cyst]]s | *[[Cyst]]s | ||
==== Eyes ==== | ====Eyes==== | ||
*Decreased [[visual acuity]] | *Decreased [[visual acuity]] | ||
*[[Cataract]] at birth | *[[Cataract]] at birth | ||
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*[[Strabismus]] | *[[Strabismus]] | ||
==== Extremities ==== | ====Extremities==== | ||
*[[Joint swelling]]: small and large joints | *[[Joint swelling]]: small and large joints | ||
*[[Arthritis]] | *[[Arthritis]] | ||
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*Joint contractures | *Joint contractures | ||
==== Neurologic ==== | ====Neurologic==== | ||
*Generalized neonatal [[hypotonia]] | *Generalized neonatal [[hypotonia]] | ||
*[[Areflexia]] | *[[Areflexia]] | ||
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*[[Delayed milestones]] | *[[Delayed milestones]] | ||
==== Other ==== | ====Other==== | ||
*[[Cryptorchidism]] | *[[Cryptorchidism]] | ||
*Skin and mucosal cysts | *Skin and mucosal cysts | ||
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*Decreased [[creatinine clearance]] | *Decreased [[creatinine clearance]] | ||
*L-carnitine lost in urine | *L-carnitine lost in urine | ||
====Blood Tests==== | ====Blood Tests==== | ||
*Raised [[ESR]] | *Raised [[ESR]] | ||
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*[[Strabismus]] and [[refraction error]]s must be corrected. | *[[Strabismus]] and [[refraction error]]s must be corrected. | ||
*[[Catarct]]s should be surgically removed, preferably in the first 6 months of life, to prevent development of [[amblyopia]]. Aphakic correction must follow the surgery. | *[[Catarct]]s should be surgically removed, preferably in the first 6 months of life, to prevent development of [[amblyopia]]. Aphakic correction must follow the surgery. | ||
===Renal function=== | ===Renal function=== | ||
*Must be monitored to look for development of [[Chronic renal failure|renal failure]], tubular wasting | *Must be monitored to look for development of [[Chronic renal failure|renal failure]], tubular wasting | ||
*[[Blood pH]] and electrolytes should be followed up. | *[[Blood pH]] and electrolytes should be followed up. | ||
===Neurologic symptoms=== | ===Neurologic symptoms=== | ||
*[[Seizure]]s should be treated with appropriate [[anticonvulsant]]s. | *[[Seizure]]s should be treated with appropriate [[anticonvulsant]]s. | ||
===Diet=== | ===Diet=== | ||
*[[Phosphate]] supplements | *[[Phosphate]] supplements | ||
*[[Carnitine]] replacement | *[[Carnitine]] replacement | ||
*[[Vitamin D]] supplementation | *[[Vitamin D]] supplementation | ||
===Behavioral therapy=== | ===Behavioral therapy=== | ||
*Behavioral modification for maladaptive behavioral patterns | *Behavioral modification for maladaptive behavioral patterns | ||
===Others=== | ===Others=== | ||
*[[Speech therapy]] and [[occupational therapy]] may be initiated as needed. | *[[Speech therapy]] and [[occupational therapy]] may be initiated as needed. | ||
===Prevention=== | |||
==References== | ==References== | ||
{{reflist|2}} | |||
{{Metabolic pathology}} | {{Metabolic pathology}} | ||
[[Category: | [[Category:Endocrinology]] | ||
{{WikiDoc Help Menu}} | {{WikiDoc Help Menu}} | ||
{{WikiDoc Sources}} | {{WikiDoc Sources}} | ||
Latest revision as of 19:28, 21 July 2016
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]
Synonyms and keywords: Lowe's syndrome
| Oculocerebrorenal syndrome | |
| ICD-10 | E72.0 |
|---|---|
| ICD-9 | 270.8 |
| OMIM | 309000 |
| DiseasesDB | 29146 |
| MeSH | D009800 |
Overview
Oculocerebrorenal syndrome is a X-linked recessive disorder characterized by hydrophthalmia, cataracts, mental retardation, aminoaciduria, reduced renal ammonia production and vitamin D-resistant rickets.
Historical Perspective
It is named after Charles Upton Lowe, who was the first to describe the condition.[1][2]
Classification
Pathophysiology
- Mutation in the OCRL gene leads to membrane defects which results in inability of proximal tubular cells to reabsorb low molecular weight proteins, bicarbonates and phosphorus.
- There is impaired intra-cellular protein folding and sorting, especially in polarized cells like renal epithelium and optic lens. This explains the pathogenesis of renal dysfunction and cataract.
Genetics
It is associated with mutation in the gene OCRL.
Causes
Differentiating Oculocerebrorenal syndrome from other diseases
Differential diagnosis
Epidemiology and Demographics
- Oculocerebrorenal syndrome is a rare disease with a prevalence of about 1 in 200,000 to 1 in every 500,000 births.
Sex
- As the disease follows an X-linked inheritance pattern, almost all affected patients are males. However, a few females with this condition have been reported.
Risk Factors
Screening
Natural History, Complications, and Prognosis
- Muscle tone improves with age, but never comes back to normal.
- Scoliosis
- Hernias
- Osteopenia
- Osteoporosis
- Rickets
- Fractures
- Metabolic acidosis
Diagnosis
History and Symptoms
- Mental retardation
- Seizures
- Febrile seizures
- Behavioral disturbances
- Temper tantrums
- Aggression
- Unusual repetitive movements
- Irritability
- Rigidity
- Preoccupations and obsessions
- Constipation
Physical Examination
Appearance of the Patient
- Small eyes
- Frontal bossing
- Elongated face
Skin
Eyes
- Decreased visual acuity
- Cataract at birth
- Glaucoma with or without buphthalmos
- Keloidss over conjunctiva and cornea without preceding trauma
- Strabismus
Extremities
- Joint swelling: small and large joints
- Arthritis
- Tenosynovitis
- Joint contractures
Neurologic
- Generalized neonatal hypotonia
- Areflexia
- Feeding difficulty
- Delayed motor development
- Delayed milestones
Other
- Cryptorchidism
- Skin and mucosal cysts
- Delayed dentition
- Dental caries
- Gingival inflammation
- Dental cysts
Laboratory Findings
Urinalysis
- Low osmolarity
- Albuminuria
- Low molecular weight proteiuria: retinol binding protein, β2 microglobulin
- Bicarbonate loss
- Aminoaciduria
- Hypercalciuria
- Hyperphosphaturia
- Decreased creatinine clearance
- L-carnitine lost in urine
Blood Tests
- Raised ESR
- High alkaline phosphatase
- Blood gases:
- Low bicarbonate levels
- Compensatory decrease in PCO2 levels
- Raised serum creatinine levels
- Serum markers: Rise in
- Acid phosphatase
- T4, TSH levels increased
Other tests
- Measurement of enzyme activity in cultured fibroblasts is the preferred test for establishing diagnosis.
X ray
- Osteopenia
- Metaphyseal flarring and cupping
MRI
- Demyelination of white matter in the periventricular area
Ultrasonography
Treatment
Ocular
- Glaucoma:
- Patients should be monitored for glaucoma
- Intraocular pressure lowering agents
- Surgery: trabeculotomy, drainage filtration device
- Corneal keloids:
- Topical steroids, lubricants
- Lamellar keratectomy, corneal transplant
- Strabismus and refraction errors must be corrected.
- Catarcts should be surgically removed, preferably in the first 6 months of life, to prevent development of amblyopia. Aphakic correction must follow the surgery.
Renal function
- Must be monitored to look for development of renal failure, tubular wasting
- Blood pH and electrolytes should be followed up.
Neurologic symptoms
- Seizures should be treated with appropriate anticonvulsants.
Diet
Behavioral therapy
- Behavioral modification for maladaptive behavioral patterns
Others
- Speech therapy and occupational therapy may be initiated as needed.
Prevention
References
- ↑ Template:WhoNamedIt
- ↑ Lowe CU, Terrey M, MacLachlan EA (1952). "Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity". A.M.A. American journal of diseases of children. 83 (2): 164–84. PMID 14884753.