Complex II deficiency

Douglas J Lanska MD MS MSPH

Neurogenetic Disorders

Updated 05.14.2024
Released 03.30.1995
Expires For CME 05.14.2027

Complex II deficiency

Author: Douglas J Lanska MD MS MSPH

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Complex II deficiency

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Introduction

Overview

Complex II deficiency results from reduction in activity of the mitochondrial enzyme succinate-ubiquinone oxido-reductase. This enzyme complex participates in the mitochondrial electron transport chain to generate ATP and serves in the Krebs cycle. Abnormalities of complex II activity are associated with a wide range of phenotypes. Most affected individuals have an encephalomyelopathy, with various degrees of CNS, skeletal muscle, and cardiac muscle involvement. CNS involvement includes microcephaly, seizures, ataxia, spasticity, developmental delay, psychiatric abnormalities, optic atrophy, oculomotor abnormalities, and radiographic abnormalities compatible with Leigh disease or leukodystrophy. Initial workup includes blood pH, lactate, pyruvate, creatine phosphokinase, and liver enzymes. Final diagnosis depends on muscle biopsy.

Key points

	• Complex II deficiency is caused by a reduction in activity of the mitochondrial enzyme succinate-ubiquinone oxido-reductase.
	• This enzyme complex participates in the mitochondrial electron transport chain to transfer reducing equivalents from succinate to coenzyme Q (as part of the process of generating ATP) and serves a dual role in the Krebs cycle (to convert succinate to fumarate).
	• Abnormalities of complex II activity are associated with a wide range of phenotypes.
	• Most affected individuals have had an encephalomyelopathy, with various degrees of central nervous system, skeletal muscle, and cardiac muscle involvement.
	• Central nervous system involvement has included microcephaly, seizure disorder, ataxia, spasticity, developmental delay, psychiatric abnormalities, optic atrophy, oculomotor abnormalities, and radiographic abnormalities compatible with Leigh disease or leukodystrophy.
	• Initial diagnostic workup of persons with complex II deficiency should include an examination of the blood pH, lactate, pyruvate, creatine phosphokinase, and liver enzymes. Final diagnosis is dependent on muscle biopsy.

Historical note and terminology

The electron transport chain, located in the inner mitochondrial membrane, is the site of oxidative phosphorylation, the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing energy that is used to reform adenosine triphosphate (ATP).

Electron transport chain

The electron transport chain is located in the inner mitochondrial membrane. It consists of various enzyme complexes that oxidize the products of the Krebs citric acid cycle to power ATP synthesis. (Image by Tim Vickers, 2007. Cou...

In this pathway, the NADH and succinate generated in the Krebs citric acid cycle are oxidized, releasing energy to power ATP synthase.

Within mitochondria, complex II links the two key cellular energy-conversion pathways: complex II serves as succinate dehydrogenase (SDH) in the Krebs cycle, and as succinate ubiquinone oxidoreductase, one of five complexes of the mitochondrial oxidative phosphorylation system. In particular, complex II couples the oxidation of succinate to fumarate in the citric acid cycle with the reduction of ubiquinone (coenzyme Q) to ubiquinol in the electron transport chain.

Complex II is a heterotetramer (ie, is protein containing four noncovalently bound subunits, wherein the subunits are not all identical) with four dissimilar subunits: SdhA, SdhB, SdhC, and SdhD.

3D schematic representation of complex II

Ribbon diagram (Richardson diagram) of complex II. The structure of the complex II (succinate dehydrogenase or succinate-ubiquinone oxidoreductase) bound to the inner phospholipid membrane of mitochondria. Complex II is a heter...

Two of these subunits are hydrophilic (SdhA and SdhB) and two are hydrophobic membrane anchor subunits (SdhC and SdhD). SdhA contains a covalently attached flavin adenine dinucleotide (FAD) cofactor and the succinate binding site. Human mitochondria contain two distinct isoforms of SdhA (Fp subunits type I and type II). SdhB contains three iron-sulfur clusters: [2Fe-2S], [4Fe-4S], and [3Fe-4S].

The subunits form a membrane-bound cytochrome b complex with six transmembrane helices containing one heme b group and a ubiquinone-binding site.

Schematic diagram of complex II

Schematic diagram of the heteromeric structure of complex II, showing its four subunits and their interaction with substrates and cofactors. Complex II couples the oxidation of succinate to fumarate with the reduction of ubiqui...
Structural model of complex II

Structural model of complex II showing the enzymatic conversions and the transfer of electrons. Electron carriers of complex II include FADH2, iron-sulfur centers, heme b, and ubiquinone. Illustration by Richard Wheeler (Zephyris)...

Two phospholipid molecules, one cardiolipin and one phosphatidylethanolamine, are also found in the SdhC and SdhD subunits in the hydrophobic space below the heme b.

Although all the elements of the respiratory chain function in the mitochondria, many of the subunits are encoded genetically in the nucleus and imported into the mitochondria. Complex II is made of four subunits (A, B, C, D), all of which are autosomally encoded (ie, encoded in the nucleus) by the succinate dehydrogenase (SDH) genes (SDHA, SDHB, SDHC, and SDHD). Other factors and cofactors needed for complex II activity are riboflavin, iron, cytochrome b560, and ubiquinone (coenzyme Q). Complex II activity is often measured together with complex III activity as succinate cytochrome C reductase activity.

Isolated complex II deficiency was first inferred in two siblings with mental retardation, seizures, myoclonus, and ataxia (48). Since that report a variety of other phenotypes have been reported, including Leigh disease (40; 13), leukodystrophy (03; 45), encephalomyopathy (29), Kearns-Sayre syndrome and other mitochondrial myopathies (49; 53), rhabdomyolysis and hemolytic uremic syndrome (42), cardiomyopathy with variable associated neurologic manifestations (psychiatric abnormalities, optic atrophy, oculomotor abnormalities, progressive polyneuropathy) (04; 53; 02; 14), and late-onset progressive neurodegeneration (55). In persons of northern Swedish descent, a myopathic phenotype due to a combination of complex II, complex III, and aconitase deficiencies has been described (24). Complex II (alone or in combination with other elements of the mitochondrial oxidative phosphorylation system) has also been reported to be abnormal in many neurodegenerative disorders, but these biochemical findings are most likely secondary events.

Clinical manifestations

Presentation and course

	• Abnormalities of complex II activity are associated with a wide range of phenotypes.
	• Most affected individuals have had an encephalomyelopathy, with various degrees of involvement of the central nervous system, skeletal muscle, and cardiac muscle.
	• Central nervous system involvement has included microcephaly, seizure disorder, ataxia, spasticity, developmental delay, psychiatric abnormalities, optic atrophy, oculomotor abnormalities, and radiographic abnormalities compatible with Leigh disease or leukodystrophy.
	• Genes for all four of the complex II subunits function as tumor suppressors, with numerous germline and somatic mutations associated with hereditary cancer syndromes, including pheochromocytoma, paraganglioma, renal cell carcinoma, and gastrointestinal stromal tumor.

Abnormalities of complex II activity are associated with a wide range of phenotypes, perhaps reflecting the underlying biochemical and genetic heterogeneity of the disorder. Factors that may influence the phenotype in any particular case include tissue and organ specificity, other enzyme involvement, and severity of the defect. Most individuals have had an encephalomyelopathy, with various degrees of central nervous system, skeletal muscle, and cardiac muscle involvement. Evidence of central nervous system involvement has included microcephaly, epileptic seizures, ataxia, spasticity, developmental delay, intellectual disability, psychiatric abnormalities, optic atrophy, oculomotor abnormalities, generalized hypotonia, and radiographic abnormalities compatible with Leigh disease or leukodystrophy (12; 03; 45; 30; 29; 14; 36; 16). Muscular involvement has generally taken the form of a slowly progressive proximal weakness, although occasional infants have had severe hypotonia and motor delay (03; 30; 53), or in one case recurrent rhabdomyolysis and hemolytic uremic syndrome (42). Cardiomyopathy is present in some patients and is associated with high mortality and morbidity (03; 30; 02; 36). Although chronic lactic acidosis is frequently present, acidotic crises have rarely been prominent (54; 58), and when present have occurred with severe liver involvement.

The phenotype may depend on which of the subunits or assembly factors of complex II is abnormal: SDHA mutations are associated with Leigh syndrome, leukodystrophy, late-onset optic atrophy, and cardiomyopathy (06; 03); SDHB mutations are associated with leukodystrophy and hypotonia (03); SDHD mutations are associated with early progressive encephalomyopathy, prenatal cardiomyopathy, and fetal or neonatal mortality (29; 02); and SDHAF1 mutations are associated with infantile leukoencephalopathy) (03; 45).

A distinct and remarkably homogenous myopathic phenotype has been described in persons of northern Swedish descent (33; 38; 59; 37; 25; 24), although a similar reported patient was not of Swedish descent (52). Affected individuals are noted to be exercise intolerant from early childhood. Muscle cramps and myoglobinuria are prominent along with hypertrophy of the calves. Acute exacerbations are precipitated by physical activity and are typified by vomiting, malaise, and increased weakness, often to the point where ambulation is precluded. Exacerbations may last up to 6 months. There is no associated encephalopathy, and many individuals have lived into adulthood. The heart is spared.

Genes for all four of the complex II subunits function as tumor suppressors, with numerous germline and somatic mutations associated with hereditary cancer syndromes, including pheochromocytoma and paraganglioma (07; 21; 44; 05; 06; 03; 17; 47; 26; 15; 10). Renal cell carcinoma may result from SDH mutations (35; 31; 60). Adrenocortical carcinoma may also be a rare manifestation of SDH mutation syndromes (17; 47). Large population studies of apparently nonsyndromic pheochromocytomas have identified a high number of germline mutations in genes of succinate dehydrogenase B and D (43; 20; 47). Other associated tumors include gastrointestinal stromal tumor, pituitary adenoma, and thyroid cancers (47; 22; 62; 27; 10). Persons inheriting an altered copy of one of these genes have a predisposition to developing these otherwise rare benign tumors at a fairly young age. However, no true enzymatic deficiency state has yet been documented in affected individuals or their tumors. The SDHAF2 gene is also a tumor suppressor, and mutations in this gene are associated with paraganglioma.

Succinate dehydrogenase deficiency may also be a contributing mechanism to the progressive β-cell failure of diabetes (34).

Prognosis and complications

The prognosis of complex II deficiency has been highly variable between different affected families. Patients with liver involvement and ketoacidotic crises have generally not survived infancy. Those with myopathy and mild or no cerebral involvement have lived into early adulthood (37). In a kindred, two siblings with age of onset in the mid-40s were alive and well at ages 56 and 62 years (55).

Clinical vignette

Case 1. A 7-year-old child diagnosed with succinate dehydrogenase deficiency had presented at 1 year of age with encephalopathy and developmental regression following viral illnesses (56). MRI abnormalities were consistent with the clinical diagnosis of Leigh syndrome. Compound heterozygous SDHA variants (c.1328C> Q and c.872A> C) were identified. Treatment with L-carnitine, riboflavin, thiamine, biotin, and ubiquinone produced only mild transient clinical improvement. He is now unable to walk and speak.

Case 2. A 21-year-old woman with succinate dehydrogenase deficiency presented with generalized muscle weakness, easy fatigability, and cardiomyopathy (56). Investigations revealed increased lactate (67.4 mg/dL; reference range 4.5 to 19.8) and plasma alanine (1,272 µmol/L; reference range 200 to 579) levels. Clinical exome sequencing revealed compound heterozygous variants at exon 15 and intron 14 of the SDHA gene.

Case 3. A 25-year-old woman with complete external ophthalmoplegia, short stature, ataxia, cardiac conduction defects, and pigmentary retinopathy compatible with the diagnosis of Kearns-Sayre syndrome was found to have an isolated deficiency of complex II (49).

Biological basis

	• Complex II deficiency is caused by a reduction in activity of the mitochondrial enzyme succinate-ubiquinone oxido-reductase.
	• In most reported cases of complex II deficiency, a specific biochemical defect has not been documented.
	• This enzyme complex participates in the mitochondrial electron transport chain to transfer reducing equivalents from succinate to coenzyme Q (as part of the process of generating ATP) and serves a dual role in the Krebs cycle (to convert succinate to fumarate).
	• In most cases in which genetic information is available, isolated complex II deficiency appears to be an autosomal recessive disease, with heterozygous carriers being completely asymptomatic.
	• Most patients have had chronic lactic acidosis, but of highly variable degrees.
	• Three of the four subunits of the complex II complex act as tumor suppressors.

Etiology and pathogenesis

Complex II deficiency is caused by a reduction in activity of the mitochondrial enzyme succinate dehydrogenase (SDH), which is also known as respiratory complex II, succinate-ubiquinone oxido-reductase, or succinate-coenzyme Q reductase (SQR), which is found in the inner mitochondrial membrane. Possible etiologies include direct alteration of one of the four subunits of the complex, or abnormalities of posttranslational processing, complex II assembly (eg, impaired function of assembly factors), mitochondrial protein importation (ie, of proteins formed in the cytosol), or postimportation processing. Loss of function in the succinate dehydrogenase enzyme complex is most often caused by an inherited mutation in one of the four SDHx genes (SDHA, SDHB, SDHC, and SDHD), a mechanism first implicated in familial phaeochromocytoma and paraganglioma (39). In the case of combined complex II and aconitase deficiency, which is most often observed in individuals of Swedish ancestry, an abnormality of proteins containing iron or iron-sulfur is postulated because of the co-involvement of several such proteins (24).

In most reported cases of complex II deficiency, a specific biochemical defect has not been documented. This enzyme complex participates in the mitochondrial electron transport chain to transfer reducing equivalents from succinate to coenzyme Q (as part of the process of generating ATP) and serves a dual role in the Krebs cycle to convert succinate to fumarate. It is also responsible for regulating mitochondrial respiratory function by responding to the cellular iron level, thereby influencing cellular growth (61). In addition, complex II is essential for Ca2+ signaling, which is necessary for mitochondrial and cellular function at multiple levels: impaired Ca2+ signaling caused by deficiency or chronic inhibition of complex II results in membrane potential loss, reduced production of ATP, and increased production of reactive oxygen species (41).

Complex II is composed of four subunits with molecular weights of 70 kd (succinate dehydrogenase A) encoded by the SDHA gene on chromosome 5p15, 27 kd (succinate dehydrogenase B) encoded by the SDHB gene on chromosome 5p15, 15 kd (succinate dehydrogenase C) encoded by the SDHC gene on chromosome 5p15, and 13 kd (succinate dehydrogenase D) encoded by the SDHD gene on chromosome 5p15.

Location of SDHA gene on chromosome 5p15

(Courtesy of the U.S. National Library of Medicine. Public domain.)
Location of SDHB gene on chromosome 1p36.1-p35

(Courtesy of the U.S. National Library of Medicine. Public domain.)
Location of SDHC gene on chromosome 1q23.3

(Courtesy of the U.S. National Library of Medicine. Public domain.)
Location of SDHD gene on chromosome 11q23

(Courtesy of the U.S. National Library of Medicine. Public domain.)

Succinate dehydrogenase contains three iron-sulfur centers and binds a single flavin adenine dinucleotide (FAD) moiety covalently. Succinate dehydrogenase is unique in having a dual role in the essential energy-producing processes of a cell: in addition to its function in reduction of ubiquinone (coenzyme Q) as part of complex II in the aerobic electron transfer chain, it also catalyzes the oxidation of succinate to fumarate in the citric acid cycle (47).

Two complex II assembly factors have been identified and characterized. Succinate dehydrogenase complex assembly factor 1 (SDHAF1), encoded by the SDHAF1 gene on chromosome 19q13.12, is a protein that resides in the mitochondria and is essential for SDH assembly, but does not physically associate with the complex in vivo.

Location of SDHAF1 gene on chromosome 19q13.12

(Courtesy of the U.S. National Library of Medicine. Public domain.)

SDHAF1 promotes maturation of the iron-sulfur protein subunit SdhB of the complex II catalytic dimer (ie, SdbA plus SdhB), and protects it from the deleterious effects of oxidants. Succinate dehydrogenase complex assembly factor 2 (SDHAF2), encoded by the SDHAF2 gene on chromosome 11q12.2, is a mitochondrial protein needed for the flavination (ie, attachment of the cofactor FAD) of a succinate dehydrogenase complex subunit required for activity of the complex.

Location of SDHAF2 gene on chromosome 11q12.2

(Courtesy of the U.S. National Library of Medicine. Public domain.)

In addition, the SDHAF2 gene is a tumor suppressor, and mutations in this gene are associated with paraganglioma. Cytochrome b560 is also associated with mature complex II.

In most cases in which genetic information is available, isolated complex II deficiency appears to be an autosomal recessive disease, with heterozygous carriers being completely asymptomatic (48; 13). Several kindreds have been reported with a Leigh disease phenotype (09; 46; 32), and a conditional mouse model of complex II deficiency has been developed that develops a Leigh-like syndrome (01). Affected patients of northern Swedish ancestry show autosomal recessive inheritance (33). In a family with the phenotype of late-onset optic atrophy, ataxia and myopathy, a missense mutation was detected on a single allele of the 70 kd subunit (SdhA) in two affected siblings, raising the possibility of autosomal-dominant inheritance (08). A recessive homozygous succinate dehydrogenase D (SDHD) mutation (ie, p.Asp92Gly) causes prenatal cardiomyopathy, a severe mitochondrial complex II deficiency, and fetal or neonatal mortality (02).

Most patients have had chronic lactic acidosis but of highly variable degrees. Two patients have had intermittent lactic acidotic crisis. All patients with elevated lactate have also had elevation in the ratio of lactate to pyruvate, as would be expected from disruption of the electron transport chain. Elevation of alanine levels is frequently seen in both blood and urine. Serum carnitine levels are uniformly low.

No detailed postmortem data are available on patients with complex II deficiency. Muscle biopsy specimens frequently show abnormal variation in fiber size and accumulation of lipid droplets; modified Gomori trichrome staining often reveals ragged-red fibers. Electron microscopic analysis of muscle mitochondria shows disruption of the normal architecture. Patients of the northern Swedish phenotype do not show ragged-red fibers but do have glycogen and lipid droplets in skeletal muscle in addition to iron-rich granular inclusions (25).

Up to two-thirds of all carotid body paragangliomas are associated with SDH deficiency (51). All four subunits of succinate dehydrogenase are tumor suppressor genes predisposing to paraganglioma, but only mutations in the SDHB subunit are associated with an increased risk of metastasis (23). Persons with mutations in the succinate dehydrogenase B (SDHB), succinate dehydrogenase C (SDHC), and succinate dehydrogenase D (SDHD) genes generally do not have a complex II deficiency in normal tissue, although complete and selective loss of complex II activity has been documented in an associated pheochromocytoma (19). Succinate dehydrogenase D (SDHD) mutation shows the most complex genetics, with autosomal dominant transmission and incomplete penetrance when maternally transmitted (07). The spectrum of mutation in succinate dehydrogenase D (SDHD) has included both truncating and nontruncating changes, and as would be expected, the trans allele is inactivated in associated tumor material. A wide spectrum of mutations is also seen in succinate dehydrogenase B (SDHB) (05), but only one kindred with a mutation at the ATG start site of succinate dehydrogenase C (SDHC) has been reported (44).

Secondary mitochondrial abnormalities have been noted in multiple neurodegenerative diseases, but a mechanism has been elucidated only in Friedreich ataxia. Frataxin, the mitochondrial protein responsible for Friedreich ataxia, functions successively as an iron chaperon and iron store by coupling iron oxidation with stepwise assembly (50; 28). The aberrant gene is thought to reduce iron availability and solubility and increase oxidative damage.

Diagnostic workup

	• Initial diagnostic workup of persons with complex II deficiency should include an examination of the blood pH, lactate, pyruvate, creatine phosphokinase, and liver enzymes.
	• Cranial imaging and EEG may be helpful in documenting the extent of cerebral involvement.
	• Initial differentiation between the various diagnostic possibilities may be made on the basis of serum lactate, pyruvate, and amino acid levels and urine organic acids.
	• Final diagnosis is dependent on muscle biopsy.

Initial diagnostic workup of persons with complex II deficiency should include an examination of the blood pH, lactate, pyruvate, creatine phosphokinase, and liver enzymes. Routine spinal fluid analysis is not indicated. EMG studies may document a subclinical myopathy. Investigation of the heart with ECG and echocardiography is imperative, as many of these individuals have had cardiac involvement, which is associated with significant mortality and morbidity.

Cranial imaging and EEG may be helpful in documenting the extent of cerebral involvement (12; 03; 45; 30; 53).

Leukencephalopathy in a patient with SDHAF1-related complex II deficiency

Cranial MRI of a 9-year-old boy with an SDHAF1 mutation (c.22C > T p.Gln8X) who presented with spasticity and clumsiness at age 20 months. Axial T2-weighted (A-C) and coronal FLAIR-weighted (D) images show widespread bilateral ...

In vivo proton magnetic resonance spectroscopy has identified a characteristic pattern in complex II deficiency: a singlet at 2.40 ppm originating from the two equivalent methylene groups of succinate (11). Accumulation of succinate in disordered cerebral white matter was also detected in a patient with SDHAF1-related complex II deficiency by in vivo proton MR spectroscopy (45).

Initial differentiation between the various diagnostic possibilities may be made on the basis of serum lactate, pyruvate, and amino acid levels and urine organic acids. Final diagnosis is dependent on muscle biopsy. Muscle biopsy specimens should first be examined for the presence of ragged-red fibers and structural abnormalities of the mitochondria (53). Enzyme histochemistry and immunohistochemistry are helpful in identifying and categorizing types of complex II deficiency (53). Enzyme activities may be measured in whole muscle preparation or isolated mitochondrial fractions. Commonly determined values are succinate dehydrogenase activity (which measures two of the four subunits of complex II), succinate cytochrome C reductase activity (which measures complex II and complex III activity), reduced nicotinamide-adenine dinucleotide cytochrome C reductase (which measures combined activities of complex I and complex III), and complex IV (cytochrome C oxidase). Although the enzymes of the electron transport chain are ubiquitously expressed, enzyme levels determined in other tissues (eg, leukocytes or fibroblasts) must be interpreted with caution because of the tissue and organ specificity of these enzymes.

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References

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45: Ohlenbusch A, Edvardson S, Skorpen J, et al. Leukoencephalopathy with accumulated succinate is indicative of SDHAF1 related complex II deficiency. Orphanet J Rare Dis 2012;7:69. PMID 22995659
46: Parfait B, Chretien D, Rotig A, Marsac C, Munnich A, Rustin P. Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome. Hum Genet 2000;106:236-43. PMID 10746566
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51: Sarkis LM, Clifton-Bligh R, Veivers D, Gill AJ. SDH deficiency is very common in carotid body paragangliomas: genetic counseling and testing should be offered to all patients. Head Neck 2023;45(6):1497-502. PMID 37010365
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53: Sonam K, Bindu PS, Taly AB, et al. Mitochondrial myopathy, cardiomyopathy, and pontine signal changes in an adult patient with isolated complex II deficiency. J Clin Neuromuscul Dis 2014;16(2):69-73. PMID 25415517
54: Sperl W, Ruitenbeek W, Trijbels JM, Sengers R, Stadhouders A, Guggenbichler J. Mitochondrial myopathy with lactic acidaemia, Fanconi-DeToni-Debre syndrome and a disturbed succinate: cytochrome C oxidoreductase activity. Eur J Pediatr 1988;147:418-21. PMID 2840289
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Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Douglas J Lanska MD MS MSPH

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health and the Medical College of Wisconsin has no relevant financial relationships to disclose.
See Profile

Former Authors

Mia MacCollin MD
Florian Eichler MD

Patient Profile

Age range of presentation: 0 month to 44 years
Sex preponderance: male=female
Heredity: heredity typical

heredity may be a factor

autosomal recessive
Population groups selectively affected: Swedes
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-10: Other specified metabolic disorders: E88.8
ICD-11: Other specified disorders of mitochondrial oxidative phosphorylation: 5C53.2Y
OMIM: Mitochondrial complex II deficiency: #252011

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Complex II deficiency

Associated Disorders

Cardiomyopathy
Kearns-Sayre syndrome
Late-onset progressive neurodegeneration
Leigh disease
Seizures

Differential Diagnosis

progressive encephalomyelopathy
lactic acidosis
MERRF
MELAS
disorders of the respiratory chain
- complex IV
- cytochrome oxidase deficiency
- disorders of pyruvate metabolism
- isolated pyruvate dehydrogenase deficiency
- pyruvate carboxylase deficiency
- disorders of oxidative phosphorylation
- alterations of the Krebs cycle
- fumarase deficiency
- organic acidopathies
- propionic acidemia
- methylmalonic acidemia
- mitochondrial encephalomyopathies
- amino acidopathies
- pheochromocytoma
- von Hippel-Lindau disease
- multiple-endocrine neoplasia type 2
- neurofibromatosis I
- hereditary paraganglioma

Also Relevant

Intellectual disability
Kearns-Sayre syndrome
Leigh syndrome
MELAS
Mitochondrial disorders
- Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome
- Myoclonus epilepsy with ragged-red fibers

Clinical Categories

Neurogenetic Disorders

Web References

Testing

Mitochondrial Disorders

Complex II deficiency

Complex II deficiency

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

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Questions or Comment?

Also in This Category

Carnitine palmitoyltransferase II deficiency

Pyruvate carboxylase deficiency

Pelizaeus-Merzbacher disease

Vanishing white matter disease

Wilson disease

Aromatic L-amino acid decarboxylase deficiency

White matter abnormalities in the brain

Hypermethioninemia

	• Prenatal detection of at-risk pregnancies has not been reported for complex II deficiency.
	• The succinate dehydrogenase B gene should be systematically tested in patients with nonsyndromic pheochromocytoma.

	• Little information is available about the treatment of complex II deficiency.
	• Based on anecdotal evidence, consideration should be given to treatment with coenzyme Q and riboflavin.

Complex II deficiency

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Carnitine palmitoyltransferase II deficiency

Pyruvate carboxylase deficiency

Pelizaeus-Merzbacher disease

Vanishing white matter disease

Wilson disease

Aromatic L-amino acid decarboxylase deficiency

White matter abnormalities in the brain

Hypermethioninemia

This is an article preview.
Start a Free Account
to access the full version.