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Methylmalonate Semialdehyde Dehydrogenase Deficiency via the ALDH6A1 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
ALDH6A1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11823ALDH6A181479 81479,81479 $990 Order Options and Pricing

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).

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


  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Methylmalonate semialdehyde dehydrogenase (MMSDH) deficiency is an inborn error of valine and thymine metabolism (Chambliss et al. 2000; Marcadier et al. 2013). To date, only four patients with molecular diagnoses have been reported in the literature, so a complete clinical picture of this disorder is not known. Thus far, the clinical phenotype and biochemical hallmarks of the disorder seem to be extremely variable (Sass et al. 2012). Patients have ranged from essentially asymptomatic with only biochemical signs of the disorder (Chambliss et al. 2000) to quite severely affected. Those with a clinical phenotype may present with vomiting and diarrhea, life-threatening ketoacidosis, severe developmental delay, post-natal microcephaly, congenital brain dysgenesis with intracerebral calcifications, and dysmorphic facial features. Biochemically, all patients have been found to have elevated 3-hydroxyisobutric acid. Other biochemical signs seem to be more variable, but may include elevated 3-aminoisobutyric acid, β-alanine and 3-hydroxypropionic acid. In addition, some patients have been found to have elevated levels of methylmalonic acid and lactic acid (Chambliss et al. 2000; Sass et al. 2012; Marcadier et al. 2013).

Dietary control has been reported to help one patient catch up developmentally to his chronological age (Sass et al. 2012).


Pathogenic variants in ALDH6A1 on chromosome 14 at 14q24.3 are responsible for autosomal recessive MMSDH deficiency. To date, fewer than 10 pathogenic variants have been reported in the ALDH6A1 gene, all of which have been missense variants (Chambliss et al. 2000; Sass et al. 2012; Marcadier et al. 2013). No variants have been reported in more than one family.

The methylmalonate semialdehyde dehydrogenase protein is involved in the catabolism of valine and thymine. More specifically, the MMSDH protein catalyzes the oxidative decarboxylation of the intermediate methylmalonic semialdehyde to propionyl-CoA (Marcadier et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, the sensitivity of this test is difficult to estimate due to the low number of cases reported in the literature. Analytical sensitivity may be high as the few reported causative variants should be detectable by sequencing (Chambliss et al. 2000; Sass et al. 2012; Marcadier et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the ALDH6A1 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

Patients with elevated 3-hydroxyisobutric acid, and potentially other biochemical disturbances as detailed above, are good candidates for this test as are those with clinical features suggestive of MMSDH deficiency. Family members of patients known to have ALDH6A1 variants are also good candidates, and we will sequence the ALDH6A1 gene to determine carrier status.


Official Gene Symbol OMIM ID
ALDH6A1 603178
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Methylmalonate Semialdehyde Dehydrogenase Deficiency AR 614105


  • Chambliss K.L. et al. 2000. Journal of Inherited Metabolic Disease. 23: 497-504. PubMed ID: 10947204
  • Marcadier J.L. et al. 2013. Orphanet Journal of Rare Diseases. 8: 98. PubMed ID: 23835272
  • Sass J.O. et al. 2012. Journal of Inherited Metabolic Disease. 35: 437-42. PubMed ID: 21863277


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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View Ordering Instructions

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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