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Sulfite oxidase deficiency(ISOD)

MedGen UID:
78695
Concept ID:
C0268624
Disease or Syndrome
Synonym: Isolated sulfite oxidase deficiency
SNOMED CT: Sulfite oxidase deficiency (367368009)
 
Gene (location): SUOX (12q13.2)
 
HPO: HP:0003643
Monarch Initiative: MONDO:0010089
OMIM®: 272300
Orphanet: ORPHA99731

Disease characteristics

Excerpted from the GeneReview: Isolated Sulfite Oxidase Deficiency
The spectrum of isolated sulfite oxidase deficiency ranges from classic early-onset (severe) disease to late-onset (mild) disease. Classic ISOD is characterized in the first few hours to days of life by intractable seizures, feeding difficulties, and rapidly progressive encephalopathy manifest as abnormal tone (especially opisthotonus, spastic quadriplegia, and pyramidal signs) followed by progressive microcephaly and profound intellectual disability. Lens subluxation or dislocation, another characteristic finding, may be evident after the newborn period. Children usually die during the first few months of life. Late-onset ISOD manifests between ages six and 18 months and is characterized by ectopia lentis (variably present), developmental delay/regression, movement disorder characterized by dystonia and choreoathetosis, ataxia, and (rarely) acute hemiplegia as a result of metabolic stroke. The clinical course may be progressive or episodic. In the episodic form encephalopathy, dystonia, choreoathetosis, and/or ataxia are intermittent. [from GeneReviews]
Authors:
Parayil Sankaran Bindu  |  Madhu Nagappa  |  Rose Dawn Bharath, et. al.   view full author information

Clinical features

From HPO
Increased urinary sulfite level
MedGen UID:
338580
Concept ID:
C1848957
Finding
The concentration of SO3(2-), i.e., sulfite, in the urine, normalized for urine concentration, is above the upper limit of normal.
Decreased urinary sulfate
MedGen UID:
338581
Concept ID:
C1848958
Finding
Decreased concentration of sulfate in the urine.
Sulfocysteinuria
MedGen UID:
419484
Concept ID:
C2931746
Disease or Syndrome
A increased concentration of sulfocysteine in the urine.
Episodic vomiting
MedGen UID:
333228
Concept ID:
C1838993
Finding
Paroxysmal, recurrent episodes of vomiting.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
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).
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Hemiplegia
MedGen UID:
9196
Concept ID:
C0018991
Sign or Symptom
Paralysis (complete loss of muscle function) in the arm, leg, and in some cases the face on one side of the body.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Agitation
MedGen UID:
88447
Concept ID:
C0085631
Sign or Symptom
A state of extreme restlessness and excessive motor activity is associated with mental distress or a feeling of inner tension.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Generalized dystonia
MedGen UID:
341342
Concept ID:
C1848954
Finding
A type of dystonia that affects all or most of the body.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Hyperintensity of cerebral white matter on MRI
MedGen UID:
811125
Concept ID:
C2938912
Pathologic Function
A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter.
Multifocal epileptiform discharges
MedGen UID:
866864
Concept ID:
C4021219
Finding
An abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG) and being identified at multiple locations (foci).
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Infantile muscular hypotonia
MedGen UID:
395993
Concept ID:
C1860834
Finding
Muscular hypotonia (abnormally low muscle tone) manifesting in infancy.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Eczema
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis. The term eczema is broadly applied to a range of persistent skin conditions and can be related to a number of underlying conditions. Manifestations of eczema can include dryness and recurring skin rashes with redness, skin edema, itching and dryness, crusting, flaking, blistering, cracking, oozing, or bleeding.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Sulfite oxidase deficiency
MedGen UID:
78695
Concept ID:
C0268624
Disease or Syndrome
The spectrum of isolated sulfite oxidase deficiency ranges from classic early-onset (severe) disease to late-onset (mild) disease. Classic ISOD is characterized in the first few hours to days of life by intractable seizures, feeding difficulties, and rapidly progressive encephalopathy manifest as abnormal tone (especially opisthotonus, spastic quadriplegia, and pyramidal signs) followed by progressive microcephaly and profound intellectual disability. Lens subluxation or dislocation, another characteristic finding, may be evident after the newborn period. Children usually die during the first few months of life. Late-onset ISOD manifests between ages six and 18 months and is characterized by ectopia lentis (variably present), developmental delay/regression, movement disorder characterized by dystonia and choreoathetosis, ataxia, and (rarely) acute hemiplegia as a result of metabolic stroke. The clinical course may be progressive or episodic. In the episodic form encephalopathy, dystonia, choreoathetosis, and/or ataxia are intermittent.
Delayed eruption of teeth
MedGen UID:
68678
Concept ID:
C0239174
Finding
Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Fine hair
MedGen UID:
98401
Concept ID:
C0423867
Finding
Hair that is fine or thin to the touch.
Ectopia lentis
MedGen UID:
41704
Concept ID:
C0013581
Congenital Abnormality
Dislocation or malposition of the crystalline lens of the eye. A partial displacement (or dislocation) of the lens is described as a subluxation of the lens, while a complete displacement is termed luxation of the lens. A complete displacement occurs if the lens is completely outside the patellar fossa of the lens, either in the anterior chamber, in the vitreous, or directly on the retina. If the lens is partially displaced but still contained within the lens space, then it is termed subluxation.
Deeply set eye
MedGen UID:
473112
Concept ID:
C0423224
Finding
An eye that is more deeply recessed into the plane of the face than is typical.
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSulfite oxidase deficiency

Conditions with this feature

Sulfite oxidase deficiency
MedGen UID:
78695
Concept ID:
C0268624
Disease or Syndrome
The spectrum of isolated sulfite oxidase deficiency ranges from classic early-onset (severe) disease to late-onset (mild) disease. Classic ISOD is characterized in the first few hours to days of life by intractable seizures, feeding difficulties, and rapidly progressive encephalopathy manifest as abnormal tone (especially opisthotonus, spastic quadriplegia, and pyramidal signs) followed by progressive microcephaly and profound intellectual disability. Lens subluxation or dislocation, another characteristic finding, may be evident after the newborn period. Children usually die during the first few months of life. Late-onset ISOD manifests between ages six and 18 months and is characterized by ectopia lentis (variably present), developmental delay/regression, movement disorder characterized by dystonia and choreoathetosis, ataxia, and (rarely) acute hemiplegia as a result of metabolic stroke. The clinical course may be progressive or episodic. In the episodic form encephalopathy, dystonia, choreoathetosis, and/or ataxia are intermittent.
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
MedGen UID:
381530
Concept ID:
C1854988
Disease or Syndrome
Molybdenum cofactor deficiency (MoCD) represents a spectrum, with some individuals experiencing significant signs and symptoms in the neonatal period and early infancy (termed early-onset or severe MoCD) and others developing signs and symptoms in childhood or adulthood (termed late-onset or mild MoCD). Individuals with early-onset MoCD typically present in the first days of life with severe encephalopathy, including refractory seizures, opisthotonos, axial and appendicular hypotonia, feeding difficulties, and apnea. Head imaging may demonstrate loss of gray and white matter differentiation, gyral swelling, sulci injury (typically assessed by evaluating the depth of focal lesional injury within the sulci), diffusely elevated T2-weighted signal, and panlobar diffusion restriction throughout the forebrain and midbrain with relative sparring of the brain stem. Prognosis for early-onset MoCD is poor, with about 75% succumbing in infancy to secondary complications of their neurologic disability (i.e., pneumonia). Late-onset MoCD is typically characterized by milder symptoms, such as acute neurologic decompensation in the setting of infection. Episodes vary in nature but commonly consist of altered mental status, dystonia, choreoathetosis, ataxia, nystagmus, and fluctuating hypotonia and hypertonia. These features may improve after resolution of the inciting infection or progress in a gradual or stochastic manner over the lifetime. Brain imaging may be normal or may demonstrate T2-weighted hyperintense or cystic lesions in the globus pallidus, thinning of the corpus callosum, and cerebellar atrophy.
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C
MedGen UID:
340761
Concept ID:
C1854990
Disease or Syndrome
Molybdenum cofactor deficiency (MoCD) represents a spectrum, with some individuals experiencing significant signs and symptoms in the neonatal period and early infancy (termed early-onset or severe MoCD) and others developing signs and symptoms in childhood or adulthood (termed late-onset or mild MoCD). Individuals with early-onset MoCD typically present in the first days of life with severe encephalopathy, including refractory seizures, opisthotonos, axial and appendicular hypotonia, feeding difficulties, and apnea. Head imaging may demonstrate loss of gray and white matter differentiation, gyral swelling, sulci injury (typically assessed by evaluating the depth of focal lesional injury within the sulci), diffusely elevated T2-weighted signal, and panlobar diffusion restriction throughout the forebrain and midbrain with relative sparring of the brain stem. Prognosis for early-onset MoCD is poor, with about 75% succumbing in infancy to secondary complications of their neurologic disability (i.e., pneumonia). Late-onset MoCD is typically characterized by milder symptoms, such as acute neurologic decompensation in the setting of infection. Episodes vary in nature but commonly consist of altered mental status, dystonia, choreoathetosis, ataxia, nystagmus, and fluctuating hypotonia and hypertonia. These features may improve after resolution of the inciting infection or progress in a gradual or stochastic manner over the lifetime. Brain imaging may be normal or may demonstrate T2-weighted hyperintense or cystic lesions in the globus pallidus, thinning of the corpus callosum, and cerebellar atrophy.

Professional guidelines

PubMed

Cornet MC, Sands TT, Cilio MR
Semin Fetal Neonatal Med 2018 Jun;23(3):204-212. Epub 2018 Jan 31 doi: 10.1016/j.siny.2018.01.004. PMID: 29426806
Sass JO, Gunduz A, Araujo Rodrigues Funayama C, Korkmaz B, Dantas Pinto KG, Tuysuz B, Yanasse Dos Santos L, Taskiran E, de Fátima Turcato M, Lam CW, Reiss J, Walter M, Yalcinkaya C, Camelo Junior JS
Brain Dev 2010 Aug;32(7):544-9. Epub 2009 Sep 29 doi: 10.1016/j.braindev.2009.09.005. PMID: 19793632
Johnson JL
Prenat Diagn 2003 Jan;23(1):6-8. doi: 10.1002/pd.505. PMID: 12533804

Recent clinical studies

Etiology

Hong SY, Lin CH
Epilepsy Behav 2023 Jun;143:109246. Epub 2023 May 13 doi: 10.1016/j.yebeh.2023.109246. PMID: 37187015
Spiegel R, Schwahn BC, Squires L, Confer N
J Inherit Metab Dis 2022 May;45(3):456-469. Epub 2022 Mar 3 doi: 10.1002/jimd.12488. PMID: 35192225Free PMC Article
Kožich V, Stabler S
J Nutr 2020 Oct 1;150(Suppl 1):2506S-2517S. doi: 10.1093/jn/nxaa134. PMID: 33000152
Claerhout H, Witters P, Régal L, Jansen K, Van Hoestenberghe MR, Breckpot J, Vermeersch P
J Inherit Metab Dis 2018 Jan;41(1):101-108. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0089-4. PMID: 28980090
Johnson JL
Prenat Diagn 2003 Jan;23(1):6-8. doi: 10.1002/pd.505. PMID: 12533804

Diagnosis

Hong SY, Lin CH
Epilepsy Behav 2023 Jun;143:109246. Epub 2023 May 13 doi: 10.1016/j.yebeh.2023.109246. PMID: 37187015
Mhanni AA, Greenberg CR, Spriggs EL, Agatep R, Sisk RR, Prasad C
Cold Spring Harb Mol Case Stud 2020 Dec;6(6) Epub 2020 Dec 17 doi: 10.1101/mcs.a005900. PMID: 33335014Free PMC Article
Cornet MC, Sands TT, Cilio MR
Semin Fetal Neonatal Med 2018 Jun;23(3):204-212. Epub 2018 Jan 31 doi: 10.1016/j.siny.2018.01.004. PMID: 29426806
Claerhout H, Witters P, Régal L, Jansen K, Van Hoestenberghe MR, Breckpot J, Vermeersch P
J Inherit Metab Dis 2018 Jan;41(1):101-108. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0089-4. PMID: 28980090
Johnson JL
Prenat Diagn 2003 Jan;23(1):6-8. doi: 10.1002/pd.505. PMID: 12533804

Therapy

Kaczmarek AT, Bahlmann N, Thaqi B, May P, Schwarz G
Mol Genet Metab 2021 Sep-Oct;134(1-2):188-194. Epub 2021 Aug 8 doi: 10.1016/j.ymgme.2021.07.011. PMID: 34420858
Wyse ATS, Grings M, Wajner M, Leipnitz G
Neurotox Res 2019 Feb;35(2):484-494. Epub 2018 Dec 5 doi: 10.1007/s12640-018-9986-z. PMID: 30515714
Cornet MC, Sands TT, Cilio MR
Semin Fetal Neonatal Med 2018 Jun;23(3):204-212. Epub 2018 Jan 31 doi: 10.1016/j.siny.2018.01.004. PMID: 29426806
Atwal PS, Scaglia F
Mol Genet Metab 2016 Jan;117(1):1-4. Epub 2015 Nov 25 doi: 10.1016/j.ymgme.2015.11.010. PMID: 26653176
Belaidi AA, Röper J, Arjune S, Krizowski S, Trifunovic A, Schwarz G
Biochem J 2015 Jul 15;469(2):211-21. doi: 10.1042/BJ20140768. PMID: 26171830

Prognosis

Spiegel R, Schwahn BC, Squires L, Confer N
J Inherit Metab Dis 2022 May;45(3):456-469. Epub 2022 Mar 3 doi: 10.1002/jimd.12488. PMID: 35192225Free PMC Article
Kaczmarek AT, Bahlmann N, Thaqi B, May P, Schwarz G
Mol Genet Metab 2021 Sep-Oct;134(1-2):188-194. Epub 2021 Aug 8 doi: 10.1016/j.ymgme.2021.07.011. PMID: 34420858
Mhanni AA, Greenberg CR, Spriggs EL, Agatep R, Sisk RR, Prasad C
Cold Spring Harb Mol Case Stud 2020 Dec;6(6) Epub 2020 Dec 17 doi: 10.1101/mcs.a005900. PMID: 33335014Free PMC Article
Tian M, Qu Y, Huang L, Su X, Li S, Ying J, Zhao F, Mu D
BMC Pediatr 2019 Dec 23;19(1):510. doi: 10.1186/s12887-019-1889-5. PMID: 31870341Free PMC Article
Claerhout H, Witters P, Régal L, Jansen K, Van Hoestenberghe MR, Breckpot J, Vermeersch P
J Inherit Metab Dis 2018 Jan;41(1):101-108. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0089-4. PMID: 28980090

Clinical prediction guides

Kaczmarek AT, Bahlmann N, Thaqi B, May P, Schwarz G
Mol Genet Metab 2021 Sep-Oct;134(1-2):188-194. Epub 2021 Aug 8 doi: 10.1016/j.ymgme.2021.07.011. PMID: 34420858
Mhanni AA, Greenberg CR, Spriggs EL, Agatep R, Sisk RR, Prasad C
Cold Spring Harb Mol Case Stud 2020 Dec;6(6) Epub 2020 Dec 17 doi: 10.1101/mcs.a005900. PMID: 33335014Free PMC Article
Wyse ATS, Grings M, Wajner M, Leipnitz G
Neurotox Res 2019 Feb;35(2):484-494. Epub 2018 Dec 5 doi: 10.1007/s12640-018-9986-z. PMID: 30515714
Claerhout H, Witters P, Régal L, Jansen K, Van Hoestenberghe MR, Breckpot J, Vermeersch P
J Inherit Metab Dis 2018 Jan;41(1):101-108. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0089-4. PMID: 28980090
Tan WH, Eichler FS, Hoda S, Lee MS, Baris H, Hanley CA, Grant PE, Krishnamoorthy KS, Shih VE
Pediatrics 2005 Sep;116(3):757-66. doi: 10.1542/peds.2004-1897. PMID: 16140720

Recent systematic reviews

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