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Infantile Leukoencephalopathy Due to Mitochondrial Complex II Deficiency via the SDHAF1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
SDHAF1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9235SDHAF181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Kym Bliven, PhD

Clinical Features and Genetics

Clinical Features

Isolated mitochondrial complex II deficiency (also known as succinate dehydrogenase deficiency) has been associated with a diverse clinical spectrum of disease, including cardiomyopathy, Leigh syndrome, infantile leukoencephalopathy, familial paraganglioma, renal cell carcinoma, and gastrointestinal stromal tumor development (Hoekstra and Bayley 2013).

Pathogenic variants in at least three genes (SDHA, SDHB, and SDHAF1) have been linked to infantile leukoencephalopathy (Hoekstra and Bayley 2013; Alston et al. 2012; Renkema et al. 2015). In patients with SDHAF1-related infantile leukoencephalopathy, symptoms generally manifest between 6-20 months following birth, and consist of rapid psychomotor regression, lack of speech development, progression of spastic quadriparesis, and partial loss of postural control with dystonia (Ghezzi et al. 2009; Ohlenbusch et al. 2012). Biochemically, this disease is characterized by elevated levels of blood lactate and pyruvate (Ghezzi et al. 2009). Succinate dehydrogenase holoenzyme quantity and activity are severely reduced in patient muscle and fibroblasts, and proton magnetic resonance spectroscopy (MRS) of the brain often reveals a high succinate peak, indicative of mitochondrial complex II deficiency. A distinctive MRI pattern has also been reported, which is delineated by cerebral hemispheric white matter abnormalities with sparing of the U fibers, corpus callosum involvement with sparing of the outer blades, and involvement of the corticospinal tracts, thalami, and spinal cord (Helman et al. 2016). 


Mitochondrial complex II deficiency, an autosomal recessive disorder, is the result of defects in the assembly or function of the mitochondrial succinate dehydrogenase (complex II) (Hoekstra and Bayley 2013). Complex II consists of four structural subunits (SDHA, SDHB, SDHC, and SDHD), while at least two accessory factors (SDHAF1 and SDHAF2) play roles in complex II assembly. Two additional accessory factors (SDHAF3 and SDHAF4) may also contribute to complex maturation, although their respective roles in this process have been less well defined (Na et al. 2014; Van Vranken et al. 2014).

The single-exon SDHAF1 gene encodes for an LYR-family assembly factor that mediates maturation of SDHB, the iron-sulfur cluster subunit of mitochondrial complex II (Na et al. 2014; Maio et al. 2016). Four pathogenic variants have been reported in the SDHAF1 gene to date, including three missense changes and one nonsense change (Ghezzi et al. 2009; Ohlenbusch et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, due to the limited number of reported cases (<15), the clinical sensitivity of SDHAF1-related mitochondrial complex II deficiency is difficult to estimate. Analytical sensitivity should be high because all pathogenic variants reported are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the SDHAF1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

SDHAF1 sequencing should be considered in patients with symptoms consistent with infantile leukoencephalopathy or a family history of this disease. We will also sequence the SDHAF1 gene to determine carrier status. 


Official Gene Symbol OMIM ID
SDHAF1 612848
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Mitochondrial Complex II Deficiency AR 252011


  • Alston C.L. et al. 2012. Journal of Medical Genetics. 49:569-77. PubMed ID: 22972948
  • Ghezzi D. et al. 2009. Nature Genetics. 41:654-6. PubMed ID: 19465911
  • Helman G. et al. 2016. Annals of Neurology. 79:379-86. PubMed ID: 26642834
  • Hoekstra A.S and Bayley J.P. 2013. Biochimica et Biophysica Acta. 1827:543-51. PubMed ID: 23174333
  • Maio N. et al. 2016. Cellular Metabolism. 23:292-302. PubMed ID: 26749241
  • Na U. et al. 2014. Cellular Metabolism. 20:253-66. PubMed ID: 24954417
  • Ohlenbusch A. et al. 2012. Orphanet Journal of Rare Diseases. 7:69. PubMed ID: 22995659
  • Renkema G.H. et al. 2015. European Journal of Human Genetics. 23:202-9. PubMed ID: 24781757
  • Van Vranken J.G. et al. 2014. Cellular Metabolism. 20:241-52. PubMed ID: 24954416


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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