For US audiences only

Expedited SSC testing, defined here to mean diagnostic results within 48 hours of when a sample is received, is available from certain laboratories, including Duke and Mayo Clinic. Other laboratories may offer expedited SSC testing services, and turnaround times may vary. The ultimate choice of laboratory is solely between the patient and the treating physician. Please contact your preferred laboratory to verify whether expedited testing is available and to confirm turnaround time.

If you are aware of another laboratory that provides expedited SSC testing or would like to have your laboratory included on this brochure, please email medical_affairs@sentynl.com. Sentynl does not subsidize any tests nor does it have any financial interests in the laboratories listed.

Click here for quick facts on MoCD
toes of a newborn with a rare genetic disorder

Molybdenum cofactor deficiency overview

What is molybdenum cofactor deficiency (MoCD)?

MoCD is a rare autosomal recessive disorder of metabolism characterized by sulfite intoxication1,2

Sulfite intoxication disorders are a group of ultra-rare inborn errors of metabolism caused by sulfite oxidase dysfunction that include isolated sulfite oxidase deficiency (ISOD) as well as MoCD Type A, Type B, and Type C.1

  • In sulfite intoxication disorders, biallelic genetic variants interrupt the sulfite oxidase pathway, leading to increased sulfite levels, especially in the brain.1,3
  • Although caused by different genetic variants, ISOD and MoCD are clinically indistinguishable.1
Spread awareness with the MoCD Type A interactive story

Genes affected in sulfite intoxication disorders1

Sulfite intoxication disorder Affected gene
ISOD SUOX
MoCD Type A MOCS1
MoCD Type B MOCS2
MoCD Type C GPHN
Spread awareness with the MoCD Type A interactive story
2 out of 3 infants with MoCD have Type A

MoCD Type A is the most common form of sulfite intoxication disorder1

MoCD Type A is rare and likely to go undiagnosed4

Worldwide incidence of MoCD Type A is estimated to be 1 per 342,000 to 411,000 live births; however, like many other rare diseases, the incidence of MoCD Type A remains uncertain and it may be underdiagnosed.4,5

MoCD Type A can affect neonates from varying populations6

Sulfite intoxication is pan-ethnic in presentation but it may be enriched in some populations.1,6 Parental consanguinity is high for children with MoCD, and a positive family history with similar presentation in siblings is often observed.1,2,7

Sulfite accumulation in MoCD Type A is caused by mutations in MOCS11,7,8

Loss of function in MOCS1 inhibits the synthesis of cyclic pyranopterin monophosphate (cPMP), leading to a loss of molybdenum cofactor (MoCo) and downstream sulfite oxidase dysfunction.8,9

Without sulfite oxidase, sulfites cannot be converted to nontoxic sulfate and neurotoxic S-sulfocysteine is formed.10

Other MoCo-dependent enzymes include xanthine oxidase, xanthine dehydrogenase, and aldehyde oxidase7,8

Although the dysfunction of these enzymes is not thought to contribute to neurotoxicity seen in MoCD Type A, their dysregulation may be helpful as biomarkers.7

MoCo-dependent enzyme dysfunction leads to3,8,11:

  • Increased taurine, xanthine, and hypoxanthine levels.
  • Low levels of uric acid in urine and plasma.

Sulfite oxidase pathway in a child with MoCD Type A4,7,8

sulfite oxidase pathway interrupted by MOCS1 deficiency in MoCD Type A

GTP, guanosine triphosphate; MPT, molybdopterin; SOX, sulfite oxidase.

caregiver holding the feet of a neonate with intractable seizures

Understanding the underlying pathophysiology of MoCD Type A can help you recognize the need to test for sulfites

Learn the signs and symptoms of sulfite intoxication in MoCD Type A.

MoCD Type A symptoms

References: 1. Spiegel R, Schwahn BC, Squires L, Confer N. Molybdenum cofactor deficiency: a natural history. J Inherit Metab Dis. 2022;45(3):456-469. 2. Zaki MS, Selim L, El-Bassyouni HT, et al. Molybdenum cofactor and isolated sulphite oxidase deficiencies: clinical and molecular spectrum among Egyptian patients. Eur J Paediatr Neurol. 2016;20(5):714-722. 3. Atwal PS, Scaglia F. Molybdenum cofactor deficiency. Mol Genet Metab. 2016;117(1):1-4. 4. Durmaz MS, Özbakır B. Molybdenum cofactor deficiency: neuroimaging findings. Radiol Case Rep. 2018;13(3):592-595. 5. Mayr SJ, et al. Forecasting the incidence of rare diseases: an iterative computational and biochemical approach in molybdenum cofactor deficiency Type A. Poster presented at: Society for the Study of Inborn Errors of Metabolism annual symposium; September 3-6, 2019; Rotterdam, The Netherlands; abstract P-567. 6. Misko A, Liang Y, Kohl J, Eichler F. Delineating the phenotypic spectrum of sulfite oxidase and molybdenum cofactor deficiency. Neurol Genet. 2020;6(4):1-10. 7. Mechler K, Mountford W, Hoffmann G, et al. Ultra-orphan diseases: a quantitative analysis of the natural history of molybdenum cofactor deficiency. Genet Med. 2015;17(12):965-970. 8. Reiss J, Hahnewald R. Molybenum cofactor deficiency: mutations in GPHN, MOCS1, and MOCS2. Hum Mutat. 2011;32(1):10-18. 9. Schwarz G. Molybdenum cofactor and human disease. Curr Opin Chem Biol. 2016;31:179-187. 10. Wyse ATS, Grings M, Wajner M, Leipnitz G. The role of oxidative stress and bioenergetic dysfunction in sulfite oxidase deficiency: insights from animal models. Neurotox Res. 2019;35(2):484-494. 11. Mellis AT, Roeper J, Misko AL, Kohl J, Schwarz G. Sulfite alters the mitochondrial network in molybdenum cofactor deficiency. Front Genet. 2021;11:594828.