Galactosemia overview: Difference between revisions
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{{Galactosemia}} | {{Galactosemia}} | ||
{{CMG}}; {{AE}} {{ | {{CMG}}; {{AE}} {{Sujaya}} | ||
==Overview== | ==Overview== | ||
Galactosemia is a | [[Galactosemia]] is a [[genetic]] [[metabolic]] [[disorder]] which affects an individual's ability to properly [[metabolize]] [[galactose]]. In individuals with [[galactosemia]], the [[enzymes]] needed for further [[metabolism]] of [[galactose]] are dysfunctional or entirely absent, leading to toxic levels of [[galactose]] and [[phosphorylated]] intermediates to build up in the [[blood]], resulting in[[liver]] and [[kidney]] failure, [[cataract]], and [[brain]] damage. | ||
==Historical Perspective== | ==Historical Perspective== | ||
The first case of [[galactosemia]] was reported in 1908. The [[disease]] was fully described in 1935 by Mason and Turner followed by elucidation of the [[gene]] in 1956. Since then, [[screening]] tests for [[galactosemia]] have been widely used. | |||
==Classification== | ==Classification== | ||
[[Galactosemia]] consists of four types of [[disorders]] resulting from abnormal activity of the [[enzymes]] involved in [[galactose]] [[metabolism]]. Type I/ Classical is the most serious form of the [[disease]]. | |||
Galactosemia | ==[[Pathophysiology]]== | ||
[[Galactose]] is an important [[metabolite]] of the human body both for [[neonatal]] and adult health, playing a vital role in [[systemic]] and [[cognitive]] development .Abnormalities in any of the [[enzymes]] involved in any of the steps of the [[Leloir]] pathway can give rise to the [[pathological]] condition called [[galactosemia]]. | |||
[[ | |||
==Causes== | ==Causes== | ||
[[Galactosemia]] is an [[autosomal]] [[recessive]] [[disorder]] which is caused by dysfunction of the [[enzymes]] involved in the [[Leloir]] pathway of [[galactose]] [[metabolism]]. | |||
==Differentiating Galactosemia from other Diseases== | ==Differentiating [[Galactosemia]] from other [[Diseases]]== | ||
Galactosemia | [[Galactosemia]] closely resembles other [[metabolic]] [[disorders]] which form important [[differential]] [[diagnoses]] in [[clinical]] practice. | ||
==[[Epidemiology]] and [[Demographics]]== | |||
== | [[Galactosemia]] is quite widespread among different countries of the world with significant [[demographic]] differences with race and ethnicity. In spite of that, typical [[symptoms]] and [[clinical]] [[signs]] are manifested in most of the patients. | ||
==[[Screening]]== | |||
[[Galactosemia]] satisfies the criteria for [[newborn]] [[screening]] successfully. Since most babies are born apparently healthy, there is a considerable window for prompt detection of the [[disease]] and appropriate intervention. | |||
==Risk Factors== | ==[[Risk]] Factors== | ||
The major [[risk]] factor for [[galactosemia]] is the presence of the defective [[gene]](s). | |||
==Natural History, Complications and Prognosis== | ==Natural History, [[Complications]] and [[Prognosis]]== | ||
[[Galactosemia]] is an [[inherited]] [[metabolic]] [[disorder]] with a variable natural history. It can lead to severe [[systemic]] [[complications]] if neglected. The [[prognosis]] depends on various factors. | |||
==[[Diagnosis]]== | |||
===History and [[Symptoms]]=== | |||
[[Galactosemia]] is primarily seen in the [[neonatal]] period with a wide range of symptoms. | |||
==Diagnosis== | |||
=== | |||
===Physical Examination=== | ===Physical Examination=== | ||
[[Galactosemia]] gives rise to varied signs on [[clinical]] examination. | |||
===Laboratory Findings=== | ===[[Laboratory]] Findings=== | ||
[[Galactosemia]] can be confirmed by a panel of [[laboratory]] [[investigations]] which provide both direct and indirect evidence of the [[disease]] by detecting abnormalities in [[blood]], [[urine]] and/or other body tissues. | |||
===Electrocardiogram=== | ===[[Electrocardiogram]]=== | ||
There are no significant [[electrocardiographic]] findings in [[galactosemia]]. | |||
===Chest X Ray=== | ===[[Chest]] [[X Ray]]=== | ||
[[Chest]] [[Xray]] is normal in [[galactosemia]]. | |||
===CT=== | ===[[CT]]=== | ||
[[CT]] Scan of the [[brain]] is useful in [[galactosemia]]. | |||
===MRI=== | ===[[MRI]]=== | ||
[[MRI]] findings of [[galactosemic]] patients indicate abnormal [[myelination]] secondary to the inability to produce sufficient and/or normal [[galactocerebroside]] due to defective [[enzyme]] activity. | |||
===Echocardiography or Ultrasound=== | ===[[Echocardiography]] or [[Ultrasound]]=== | ||
[[Echocardiography]] is not useful in the [[diagnosis]] of [[galactosemia]]. On the other hand, [[ultrasonography]] provides useful information. | |||
===Other Imaging Findings=== | ===Other [[Imaging]] Findings=== | ||
Additional [[imaging]] with diffusion weighted [[MRI]] and [[radionuclides]] also aid in the [[diagnosis]] of [[galactosemia]]. | |||
===Other Diagnostic Studies=== | ===Other [[Diagnostic]] Studies=== | ||
In addition to the commonly performed laboratory tests, [[histopathology]] and [[genetics]] also aid in confirmation of [[galactosemia]]. | |||
==Treatment== | ==Treatment== | ||
===Medical Therapy=== | ===[[Medical]] [[Therapy]]=== | ||
[[Medical]] [[therapy]] is of limited importance in [[galactosemia]]. | |||
===[[Surgery]]=== | |||
===Surgery=== | [[Surgical]]treatment is rarely indicated for management of [[galactosemia]]. | ||
===[[Primary]] [[Prevention]]=== | |||
Preventive strategies of [[galactosemia]] are primarily aimed at early [[detection]] through [[screening]] and prompt intervention. | |||
===Primary Prevention=== | |||
===Secondary Prevention=== | ===[[Secondary]] [[Prevention]]=== | ||
[[Secondary]] [[prevention]] of [[galactosemia]] consists of [[newborn]] [[screening]] and [[dietary]] modifications. | |||
===Cost-Effectiveness of Therapy=== | ===Cost-Effectiveness of [[Therapy]]=== | ||
The cost-effectiveness of the therapy of [[galactosemia]] has primarily been studied with respect to the [[screening]] program for the [[disease]] and the benefits reaped from it. | |||
===Future or Investigational Therapies=== | ===Future or [[Investigational]] [[Therapies]]=== | ||
A number of [[therapeutic]] modalities are currently being explored. | |||
==Case Studies== | ==Case Studies== | ||
Latest revision as of 00:17, 6 July 2022
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Galactosemia overview On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]
Overview
Galactosemia is a genetic metabolic disorder which affects an individual's ability to properly metabolize galactose. In individuals with galactosemia, the enzymes needed for further metabolism of galactose are dysfunctional or entirely absent, leading to toxic levels of galactose and phosphorylated intermediates to build up in the blood, resulting inliver and kidney failure, cataract, and brain damage.
Historical Perspective
The first case of galactosemia was reported in 1908. The disease was fully described in 1935 by Mason and Turner followed by elucidation of the gene in 1956. Since then, screening tests for galactosemia have been widely used.
Classification
Galactosemia consists of four types of disorders resulting from abnormal activity of the enzymes involved in galactose metabolism. Type I/ Classical is the most serious form of the disease.
Pathophysiology
Galactose is an important metabolite of the human body both for neonatal and adult health, playing a vital role in systemic and cognitive development .Abnormalities in any of the enzymes involved in any of the steps of the Leloir pathway can give rise to the pathological condition called galactosemia.
Causes
Galactosemia is an autosomal recessive disorder which is caused by dysfunction of the enzymes involved in the Leloir pathway of galactose metabolism.
Differentiating Galactosemia from other Diseases
Galactosemia closely resembles other metabolic disorders which form important differential diagnoses in clinical practice.
Epidemiology and Demographics
Galactosemia is quite widespread among different countries of the world with significant demographic differences with race and ethnicity. In spite of that, typical symptoms and clinical signs are manifested in most of the patients.
Screening
Galactosemia satisfies the criteria for newborn screening successfully. Since most babies are born apparently healthy, there is a considerable window for prompt detection of the disease and appropriate intervention.
Risk Factors
The major risk factor for galactosemia is the presence of the defective gene(s).
Natural History, Complications and Prognosis
Galactosemia is an inherited metabolic disorder with a variable natural history. It can lead to severe systemic complications if neglected. The prognosis depends on various factors.
Diagnosis
History and Symptoms
Galactosemia is primarily seen in the neonatal period with a wide range of symptoms.
Physical Examination
Galactosemia gives rise to varied signs on clinical examination.
Laboratory Findings
Galactosemia can be confirmed by a panel of laboratory investigations which provide both direct and indirect evidence of the disease by detecting abnormalities in blood, urine and/or other body tissues.
Electrocardiogram
There are no significant electrocardiographic findings in galactosemia.
Chest X Ray
Chest Xray is normal in galactosemia.
CT
CT Scan of the brain is useful in galactosemia.
MRI
MRI findings of galactosemic patients indicate abnormal myelination secondary to the inability to produce sufficient and/or normal galactocerebroside due to defective enzyme activity.
Echocardiography or Ultrasound
Echocardiography is not useful in the diagnosis of galactosemia. On the other hand, ultrasonography provides useful information.
Other Imaging Findings
Additional imaging with diffusion weighted MRI and radionuclides also aid in the diagnosis of galactosemia.
Other Diagnostic Studies
In addition to the commonly performed laboratory tests, histopathology and genetics also aid in confirmation of galactosemia.
Treatment
Medical Therapy
Medical therapy is of limited importance in galactosemia.
Surgery
Surgicaltreatment is rarely indicated for management of galactosemia.
Primary Prevention
Preventive strategies of galactosemia are primarily aimed at early detection through screening and prompt intervention.
Secondary Prevention
Secondary prevention of galactosemia consists of newborn screening and dietary modifications.
Cost-Effectiveness of Therapy
The cost-effectiveness of the therapy of galactosemia has primarily been studied with respect to the screening program for the disease and the benefits reaped from it.
Future or Investigational Therapies
A number of therapeutic modalities are currently being explored.