Complex II deficiency-A case report and review of the literature

Shailly Jain-Ghai, Jessie M. Cameron, Almundher Al Maawali, Susan Blaser, Nevena Mackay, Brian Robinson, Julian Raiman

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Complex II deficiency is a rare cause of mitochondrial respiratory chain defects with a prevalence of 2-23%. It is exclusively nuclear encoded and functions in the citric acid cycle by oxidizing succinate to fumarate and in the mitochondrial electron transport chain (ETC) by transferring electrons to ubiquinone. Of the four subunits, SDHA and SDHB are catalytic and SDHC and SDHD are anchoring. Mutations in SDHA and SDHAF1 (assembly factor) have been found in patients with CII deficiency and a mitochondrial phenotype. We present a patient with CII deficiency with a previously undescribed phenotype of dilated cardiomyopathy, left ventricular noncompaction, failure to thrive, hypotonia, and developmental delay. Also, a comprehensive review of 36 cases published in the literature was undertaken. The results show that CII deficiency has a variable phenotype with no correlation with residual complex activity in muscle although the phenotype and enzyme activities are comparable within a family. For some, the condition was fatal in infancy, others had multisystem involvement and some had onset in adulthood with mild symptoms and normal cognition. Neurological involvement is most commonly observed and brain imaging commonly shows leukoencephalopathy, Leigh syndrome, or cerebellar atrophy. Mutations in SDHAF1 are associated with leukoencephalopathy. Other organ systems like heart, muscle, and eyes are only involved in about 50% of the cases but cardiomyopathy is associated with high mortality and morbidity. In some patients, riboflavin has provided clinical improvement.

Original languageEnglish
Pages (from-to)285-294
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number2
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Phenotype
Leukoencephalopathies
Electron Transport
Leigh Disease
Failure to Thrive
Fumarates
Mutation
Muscle Hypotonia
Ubiquinone
Citric Acid Cycle
Riboflavin
Dilated Cardiomyopathy
Succinic Acid
Cardiomyopathies
Neuroimaging
Cognition
Atrophy
Myocardium
Electrons
Morbidity

Keywords

  • Complex II
  • Mitochondrial disorder
  • SDHA
  • SDHAF1
  • Succinate dehydrogenase

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Jain-Ghai, S., Cameron, J. M., Al Maawali, A., Blaser, S., Mackay, N., Robinson, B., & Raiman, J. (2013). Complex II deficiency-A case report and review of the literature. American Journal of Medical Genetics, Part A, 161(2), 285-294. https://doi.org/10.1002/ajmg.a.35714

Complex II deficiency-A case report and review of the literature. / Jain-Ghai, Shailly; Cameron, Jessie M.; Al Maawali, Almundher; Blaser, Susan; Mackay, Nevena; Robinson, Brian; Raiman, Julian.

In: American Journal of Medical Genetics, Part A, Vol. 161, No. 2, 02.2013, p. 285-294.

Research output: Contribution to journalArticle

Jain-Ghai, S, Cameron, JM, Al Maawali, A, Blaser, S, Mackay, N, Robinson, B & Raiman, J 2013, 'Complex II deficiency-A case report and review of the literature', American Journal of Medical Genetics, Part A, vol. 161, no. 2, pp. 285-294. https://doi.org/10.1002/ajmg.a.35714
Jain-Ghai, Shailly ; Cameron, Jessie M. ; Al Maawali, Almundher ; Blaser, Susan ; Mackay, Nevena ; Robinson, Brian ; Raiman, Julian. / Complex II deficiency-A case report and review of the literature. In: American Journal of Medical Genetics, Part A. 2013 ; Vol. 161, No. 2. pp. 285-294.
@article{7f15aca1b00941d2867dd65c9ae0f393,
title = "Complex II deficiency-A case report and review of the literature",
abstract = "Complex II deficiency is a rare cause of mitochondrial respiratory chain defects with a prevalence of 2-23{\%}. It is exclusively nuclear encoded and functions in the citric acid cycle by oxidizing succinate to fumarate and in the mitochondrial electron transport chain (ETC) by transferring electrons to ubiquinone. Of the four subunits, SDHA and SDHB are catalytic and SDHC and SDHD are anchoring. Mutations in SDHA and SDHAF1 (assembly factor) have been found in patients with CII deficiency and a mitochondrial phenotype. We present a patient with CII deficiency with a previously undescribed phenotype of dilated cardiomyopathy, left ventricular noncompaction, failure to thrive, hypotonia, and developmental delay. Also, a comprehensive review of 36 cases published in the literature was undertaken. The results show that CII deficiency has a variable phenotype with no correlation with residual complex activity in muscle although the phenotype and enzyme activities are comparable within a family. For some, the condition was fatal in infancy, others had multisystem involvement and some had onset in adulthood with mild symptoms and normal cognition. Neurological involvement is most commonly observed and brain imaging commonly shows leukoencephalopathy, Leigh syndrome, or cerebellar atrophy. Mutations in SDHAF1 are associated with leukoencephalopathy. Other organ systems like heart, muscle, and eyes are only involved in about 50{\%} of the cases but cardiomyopathy is associated with high mortality and morbidity. In some patients, riboflavin has provided clinical improvement.",
keywords = "Complex II, Mitochondrial disorder, SDHA, SDHAF1, Succinate dehydrogenase",
author = "Shailly Jain-Ghai and Cameron, {Jessie M.} and {Al Maawali}, Almundher and Susan Blaser and Nevena Mackay and Brian Robinson and Julian Raiman",
year = "2013",
month = "2",
doi = "10.1002/ajmg.a.35714",
language = "English",
volume = "161",
pages = "285--294",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Complex II deficiency-A case report and review of the literature

AU - Jain-Ghai, Shailly

AU - Cameron, Jessie M.

AU - Al Maawali, Almundher

AU - Blaser, Susan

AU - Mackay, Nevena

AU - Robinson, Brian

AU - Raiman, Julian

PY - 2013/2

Y1 - 2013/2

N2 - Complex II deficiency is a rare cause of mitochondrial respiratory chain defects with a prevalence of 2-23%. It is exclusively nuclear encoded and functions in the citric acid cycle by oxidizing succinate to fumarate and in the mitochondrial electron transport chain (ETC) by transferring electrons to ubiquinone. Of the four subunits, SDHA and SDHB are catalytic and SDHC and SDHD are anchoring. Mutations in SDHA and SDHAF1 (assembly factor) have been found in patients with CII deficiency and a mitochondrial phenotype. We present a patient with CII deficiency with a previously undescribed phenotype of dilated cardiomyopathy, left ventricular noncompaction, failure to thrive, hypotonia, and developmental delay. Also, a comprehensive review of 36 cases published in the literature was undertaken. The results show that CII deficiency has a variable phenotype with no correlation with residual complex activity in muscle although the phenotype and enzyme activities are comparable within a family. For some, the condition was fatal in infancy, others had multisystem involvement and some had onset in adulthood with mild symptoms and normal cognition. Neurological involvement is most commonly observed and brain imaging commonly shows leukoencephalopathy, Leigh syndrome, or cerebellar atrophy. Mutations in SDHAF1 are associated with leukoencephalopathy. Other organ systems like heart, muscle, and eyes are only involved in about 50% of the cases but cardiomyopathy is associated with high mortality and morbidity. In some patients, riboflavin has provided clinical improvement.

AB - Complex II deficiency is a rare cause of mitochondrial respiratory chain defects with a prevalence of 2-23%. It is exclusively nuclear encoded and functions in the citric acid cycle by oxidizing succinate to fumarate and in the mitochondrial electron transport chain (ETC) by transferring electrons to ubiquinone. Of the four subunits, SDHA and SDHB are catalytic and SDHC and SDHD are anchoring. Mutations in SDHA and SDHAF1 (assembly factor) have been found in patients with CII deficiency and a mitochondrial phenotype. We present a patient with CII deficiency with a previously undescribed phenotype of dilated cardiomyopathy, left ventricular noncompaction, failure to thrive, hypotonia, and developmental delay. Also, a comprehensive review of 36 cases published in the literature was undertaken. The results show that CII deficiency has a variable phenotype with no correlation with residual complex activity in muscle although the phenotype and enzyme activities are comparable within a family. For some, the condition was fatal in infancy, others had multisystem involvement and some had onset in adulthood with mild symptoms and normal cognition. Neurological involvement is most commonly observed and brain imaging commonly shows leukoencephalopathy, Leigh syndrome, or cerebellar atrophy. Mutations in SDHAF1 are associated with leukoencephalopathy. Other organ systems like heart, muscle, and eyes are only involved in about 50% of the cases but cardiomyopathy is associated with high mortality and morbidity. In some patients, riboflavin has provided clinical improvement.

KW - Complex II

KW - Mitochondrial disorder

KW - SDHA

KW - SDHAF1

KW - Succinate dehydrogenase

UR - http://www.scopus.com/inward/record.url?scp=84872947433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872947433&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.35714

DO - 10.1002/ajmg.a.35714

M3 - Article

VL - 161

SP - 285

EP - 294

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

IS - 2

ER -