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Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate(ARLIAK)

MedGen UID:
1677730
Concept ID:
C5193068
Disease or Syndrome
Synonyms: ARLIAK; LEUKOENCEPHALOPATHY, ACUTE REVERSIBLE, WITH INCREASED URINARY ALPHA-KETOGLUTARATE
SNOMED CT: Acute reversible leukoencephalopathy due to sodium-dependent dicarboxylate transporter deficiency (1340040004); Acute reversible leukoencephalopathy due to SLC13A3 deficiency (1340040004); Acute reversible leukoencephalopathy with increased urinary alpha-ketoglutarate (1340040004)
 
Gene (location): SLC13A3 (20q13.12)
 
Monarch Initiative: MONDO:0032716
OMIM®: 618384
Orphanet: ORPHA615964

Definition

Acute reversible leukoencephalopathy with increased urinary alpha-ketoglutarate (ARLIAK) is an autosomal recessive disorder characterized by acute reversible neurologic deterioration in the context of a febrile illness. The disorder is associated with transient leukoencephalopathy on brain imaging concurrent with the acute episode, as well as persistently increased excretion of dicarboxylic acids, particularly alpha-ketoglutarate (summary by Dewulf et al., 2019). [from OMIM]

Clinical features

From HPO
Increased urine alpha-ketoglutarate concentration
MedGen UID:
868516
Concept ID:
C4022915
Finding
A greater than normal concentration of 2-oxoglutaric acid in the urine.
Increased urine succinate level
MedGen UID:
1771435
Concept ID:
C5421603
Finding
The concentration of succinate in the urine, normalized for urine concentration, is above the upper limit of normal.
Elevated urine N-acetylaspartic acid level
MedGen UID:
1841756
Concept ID:
C5826558
Finding
The amount of N-acetylaspartate in the urine, when corrected for urine concentration, is above upper limit of normal. This feature can be measured using gas chromatography-mass spectrometry.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Febrile seizure (within the age range of 3 months to 6 years)
MedGen UID:
3232
Concept ID:
C0009952
Disease or Syndrome
A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years.
Drowsiness
MedGen UID:
4390
Concept ID:
C0013144
Finding
Abnormal feeling of sleepiness or difficulty staying awake.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
CSF pleocytosis
MedGen UID:
56247
Concept ID:
C0151857
Disease or Syndrome
An increased white blood cell count in the cerebrospinal fluid.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Increased CSF lactate
MedGen UID:
257904
Concept ID:
C1167918
Finding
Increased concentration of lactate in the cerebrospinal fluid.
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
Elevated CSF alpha-ketoglutarate concentration
MedGen UID:
1052707
Concept ID:
CN377300
Finding
The concentration of alpha-ketoglutarate in the cerebrospinal fluid (CSF) is above the upper limit of normal.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLeukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate

Recent clinical studies

Diagnosis

Kon FC, Hoggard N, Gillett G, Hadjivassiliou M
Pract Neurol 2023 Oct;23(5):411-413. Epub 2023 Jun 8 doi: 10.1136/pn-2023-003725. PMID: 37290914
Dewulf JP, Wiame E, Dorboz I, Elmaleh-Bergès M, Imbard A, Dumitriu D, Rak M, Bourillon A, Helaers R, Malla A, Renaldo F, Boespflug-Tanguy O, Vincent MF, Benoist JF, Wevers RA, Schlessinger A, Van Schaftingen E, Nassogne MC, Schiff M
Ann Neurol 2019 Mar;85(3):385-395. Epub 2019 Jan 29 doi: 10.1002/ana.25412. PMID: 30635937

Clinical prediction guides

Dewulf JP, Wiame E, Dorboz I, Elmaleh-Bergès M, Imbard A, Dumitriu D, Rak M, Bourillon A, Helaers R, Malla A, Renaldo F, Boespflug-Tanguy O, Vincent MF, Benoist JF, Wevers RA, Schlessinger A, Van Schaftingen E, Nassogne MC, Schiff M
Ann Neurol 2019 Mar;85(3):385-395. Epub 2019 Jan 29 doi: 10.1002/ana.25412. PMID: 30635937