Arginemia: Difference between revisions
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[[Image:autorecessive.jpg|thumb|left|Arginase deficiency is inherited in an [[Recessive gene|autosomal recessive]] pattern.]] | [[Image:autorecessive.jpg|thumb|left|Arginase deficiency is inherited in an [[Recessive gene|autosomal recessive]] pattern.]] | ||
This condition is inherited in an [[autosomal recessive]] pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder. | This condition is inherited in an [[autosomal recessive]] pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder. | ||
==Differential diagnosis== | |||
Arginase deficiency must be differentiated from other diseases that cause neurological manifestations in infants. | |||
{| | |||
|- style="background: #4479BA; color: #FFFFFF; text-align: center;" | |||
! rowspan="2" |Diseases | |||
! colspan="4" |Type of motor abnormality | |||
! rowspan="2" |Clinical findings | |||
! rowspan="2" |Laboratory findings and diagnostic tests | |||
! rowspan="2" |Radiographic findings | |||
|- style="background: #4479BA; color: #FFFFFF; text-align: center;" | |||
!Spasticity | |||
!Hypotonia | |||
!Ataxia | |||
!Dystonia | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Leigh syndrome]] | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki> | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Progressive [[psychomotor]] regression | |||
* [[Seizures]] | |||
* External [[ophthalmoplegia]] | |||
* [[Lactic acidosis]] | |||
* [[Vomiting]] | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Increased [[lactate]] levels in [[blood]] and [[CSF]] | |||
* Genetic testing | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* MRI: abnormal [[white matter]] signal in the [[putamen]], [[basal ganglia]], and [[brainstem]] on T2 images | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Niemann-Pick]] disease type C | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Progressive [[neurodegeneration]] | |||
* [[Hepatosplenomegaly]] | |||
* Systemic involvement of [[liver]], [[spleen]], or [[lung]] preceedes [[neurologic]] symptoms | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Abnormal [[liver]] function tests | |||
* [[Fibroblast]] cell culture with filipin staining | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* MRI: | |||
**[[Cerebral]] and [[cerebellar]] [[atrophy]] | |||
**Thinning of the [[corpus callosum]] | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Infantile Refsum disease | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Abnormalities of the [[optic nerve]] and disc | |||
* [[Retinitis pigmentosa]] | |||
* [[Sensorineural]] hearing loss | |||
* [[Hepatomegaly]] and [[cirrhosis]] | |||
* [[Neurologic]] deterioration is slower than in [[Zellweger syndrome]] or ALD | |||
| style="background: #F5F5F5; padding: 5px;" |Elevated plasma VLCFA levels | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Adrenoleukodystrophy]] | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* [[Cognitive]] and behavioral abnormalities | |||
* [[Adrenal insufficiency]] | |||
* [[Hyperpigmented]] skin | |||
* [[Gonadal dysfunction]] | |||
* [[Neurologic]] deterioration progresses at a variable rate | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Elevated plasma VLCFA levels | |||
* Molecular [[genetic testing]] for mutations in the ABCD1 gene | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Zellweger syndrome]] | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* [[Craniofacial]] dysmorphism | |||
* [[Hepatomegaly]] | |||
* Neonatal [[seizures]] | |||
* Profound developmental delay | |||
* [[MRI]] findings include [[cortical]] and [[white matter]] abnormalities | |||
* [[Neurologic deterioration]] is rapid and infants rarely survive beyond six months of age | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Elevated plasma VLCFA levels | |||
* Elevated levels of [[phytanic acid]], pristanic acid, and pipecolic acid in plasma and [[fibroblasts]] | |||
* Reduced plasmalogen in [[erythrocytes]] | |||
* Molecular [[genetic]] testing for [[mutations]] in the PEX1 or PEX6 genes | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pyruvate dehydrogenase deficiency]] | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* [[Lactic acidosis]] | |||
* [[Seizures]] | |||
* [[Intellectual disability]] | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Elevated [[lactate]] and pyruvate levels in [[blood]] and CSF | |||
* Abnormal PDH enzymatic activity in cultured fibroblasts | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Arginase deficiency]] | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* [[Hyperammonemia]] | |||
* [[Encephalopathy]] | |||
* [[Respiratory alkalosis]] | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Elevated [[ammonia]] level | |||
* Elevated [[arginine]] level | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Holocarboxylase synthetase deficiency | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* [[Ketoacidosis]] | |||
* [[Dermatitis]] | |||
* [[Alopecia]] | |||
* [[Seizures]] | |||
* [[Developmental delay]] | |||
| style="background: #F5F5F5; padding: 5px;" |Elevated levels of: | |||
* Beta-hydroxyisovalerate | |||
* Beta-methylcrotonylglycine | |||
* Beta-hydroxypropionate | |||
* Methylcitrate | |||
* Tiglylglycine | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Glutaric aciduria type 1 | |||
| style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki> | |||
| style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki> | |||
| style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki> | |||
| style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki> | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Episodes of [[metabolic decompensation]] and [[encephalopathy]] often precipitated by [[infection]] and [[fever]] | |||
* Rarely presents in the newborn period | |||
* Microencephalic [[macrocephaly]] | |||
* [[Seizures]] (approximately 20 percent) | |||
* [[Cognitive function]] is preserved | |||
| style="background: #F5F5F5; padding: 5px;" |Elevated levels of: | |||
* [[glutaric acid]] | |||
* 3-hydroxyglutaric acid | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* MRI: | |||
**[[Frontal]] and [[temporal]] [[atrophy]] | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Ataxia telangiectasia]] | |||
| style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki> | |||
| style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki> | |||
| style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki> | |||
| style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki> | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Progressive [[cerebellar]] [[ataxia]] | |||
* Abnormal eye movements | |||
* [[Oculocutaneous]] [[telangiectasias]] | |||
* Immune deficiency | |||
* Increased risk of [[malignancy]] | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Elevated serum alpha-fetoprotein level | |||
* Low [[IgA]] and [[IgG]] levels | |||
* [[Lymphopenia]] | |||
* Genetic testing for [[mutation]] in the ATM gene | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pontocerebellar]] [[hypoplasias]] | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Progressive muscle [[atrophy]] | |||
* [[Microcephaly]] | |||
* [[Developmental delay]] | |||
| style="background: #F5F5F5; padding: 5px;" |[[Genetic]] testing for PCH gene mutations | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* MRI : | |||
**Small [[cerebellum]] and [[brainstem]] including the [[pons]] | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Metachromatic leukodystrophy]] | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Regression of motor skills | |||
* [[Seizures]] | |||
* [[Optic atrophy]] | |||
* Reduced or absent [[deep tendon reflexes]] | |||
* [[Intellectual disability]] | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Deficient arylsulfatase A enzyme activity in [[leukocytes]] or cultured skin fibroblasts | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pelizaeus-Merzbacher]] | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* [[Nystagmus]] | |||
* [[Cognitive impairment]] | |||
* Onset in infancy | |||
* Slowly progressive | |||
* Language development may be normal | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* [[Genetic]] testing for [[mutations]] in PLP1 gene | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
*MRI: | |||
**[[White matter]] abnormalities | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Angelman syndrome]] | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Profound [[intellectual disability]] | |||
* Postnatal [[microcephaly]] | |||
* Typical abnormal behaviors (paroxysmal laughter, easily excitable) | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Methylation studies and [[chromosome]] microarray to detect chromosome 15 anomalies and UBE3A mutations | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Rett syndrome]] | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Occurs almost exclusively in females | |||
* Normal development during first six months followed by regression and loss of milestones | |||
* Loss of speech capability | |||
* Stereotypic hand movements | |||
* [[Seizures]] | |||
* [[Autistic]] features | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Clinical diagnosis | |||
* [[Genetic]] testing for MECP2 mutations | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Lesch-Nyhan syndrome]] | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* [[Self-mutilating]] behavior | |||
* [[Urinary]] stones due to [[hyperuricemia]] | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Elevated [[uric acid]] level | |||
* Abnormal enzymatic activity of HPRT in cultured fibroblasts | |||
* [[Genetic]] testing for HPRT gene [[mutations]] | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Miller-Dieker lissencephaly | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* [[Lissencephaly]] | |||
* [[Microcephaly]] | |||
* [[Dysmorphic]] features | |||
* [[Seizures]] | |||
* Failure to thrive | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Cytogenetic testing for 17p13.3 microdeletion | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|- | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Dopa-responsive [[dystonia]] | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | - | |||
| style="background: #F5F5F5; padding: 5px;" | + | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Onset in early childhood | |||
* Symptoms worsen with [[fatigue]] and exercise | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
* Positive response to a trial of [[levodopa]] | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;" |-- | |||
|} | |||
==References== | ==References== |
Latest revision as of 15:57, 9 October 2017
Arginemia | |
![]() | |
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Arginine | |
OMIM | 207800 |
DiseasesDB | 29677 |
eMedicine | ped/132 |
MeSH | D020162 |
WikiDoc Resources for Arginemia |
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Most recent articles on Arginemia |
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Evidence Based Medicine |
Clinical Trials |
Ongoing Trials on Arginemia at Clinical Trials.gov Clinical Trials on Arginemia at Google
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US National Guidelines Clearinghouse on Arginemia
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Books |
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Definitions |
Patient Resources / Community |
Patient resources on Arginemia Discussion groups on Arginemia Directions to Hospitals Treating Arginemia Risk calculators and risk factors for Arginemia
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Continuing Medical Education (CME) |
International |
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Business |
Experimental / Informatics |
Arginemia (also called arginase deficiency) is a congenital disorder where arginase deficiency causes a high level of arginine and ammonia in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.
Arginase deficiency usually becomes evident by about the age of 3. It most often appears as stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity). Other symptoms may include slower than normal growth, developmental delay and eventual loss of developmental milestones, mental retardation, seizures, tremor, and difficulty with balance and coordination (ataxia). Occasionally, high protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase in ammonia may lead to episodes of irritability, refusal to eat, and vomiting.
In some affected individuals, signs and symptoms of arginase deficiency may be less severe, and may not appear until later in life.
Mutations in the ARG1 gene cause arginase deficiency. Arginase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.
The ARG1 gene provides instructions for making an enzyme called arginase. This enzyme controls the final step of the urea cycle, which produces urea by removing nitrogen from arginine. In people with arginase deficiency, arginase is damaged or missing, and arginine is not broken down properly. As a result, urea cannot be produced normally, and excess nitrogen accumulates in the blood in the form of ammonia. The accumulation of ammonia and arginine are believed to cause the neurological problems and other signs and symptoms of arginase deficiency.

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.
Differential diagnosis
Arginase deficiency must be differentiated from other diseases that cause neurological manifestations in infants.
Diseases | Type of motor abnormality | Clinical findings | Laboratory findings and diagnostic tests | Radiographic findings | |||
---|---|---|---|---|---|---|---|
Spasticity | Hypotonia | Ataxia | Dystonia | ||||
Leigh syndrome | - | - | + | + |
|
| |
Niemann-Pick disease type C | - | - | + | + |
|
|
|
Infantile Refsum disease | - | + | + | - |
|
Elevated plasma VLCFA levels | -- |
Adrenoleukodystrophy | + | - | - | - |
|
|
-- |
Zellweger syndrome | - | + | - | - |
|
|
-- |
Pyruvate dehydrogenase deficiency | + | + | + | - | -- | ||
Arginase deficiency | + | - | - | - | -- | ||
Holocarboxylase synthetase deficiency | - | + | - | - | Elevated levels of:
|
-- | |
Glutaric aciduria type 1 | - | - | - | + |
|
Elevated levels of:
|
|
Ataxia telangiectasia | - | - | + | - |
|
|
-- |
Pontocerebellar hypoplasias | - | + | - | - |
|
Genetic testing for PCH gene mutations |
|
Metachromatic leukodystrophy | - | + | + | - |
|
|
-- |
Pelizaeus-Merzbacher | + | - | + | - |
|
| |
Angelman syndrome | - | - | + | - |
|
|
-- |
Rett syndrome | + | - | - | + |
|
-- | |
Lesch-Nyhan syndrome | + | - | - | + |
|
-- | |
Miller-Dieker lissencephaly | + | + | - | - |
|
|
-- |
Dopa-responsive dystonia | + | - | - | + |
|
|
-- |