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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.

toes of an infant with a sulfite intoxication diagnosis

How is MoCD Type A diagnosed?

Underdiagnosis of MoCD Type A in neonates is likely due to the overlap in presentation with other, more common disorders1

Although symptoms of MoCD Type A often present on the first day of life, reaching the right diagnosis may take more time if the necessary diagnostic steps are not taken.2

Differential diagnosis of MoCD Type A based on clinical signs and symptoms of neonatal seizures and encephalopathy includes1,3:

  • Hypoxic-ischemic encephalopathy (HIE)
  • Isolated sulfite oxidase deficiency (ISOD)
  • Other inborn errors of metabolism
    • Peroxisomal disorders
    • Pyridoxine-dependent epilepsy
    • GAMT deficiency
    • ADSL deficiency
    • GLUT1 deficiency
    • GABA transaminase deficiency
    • Amino acid disorders (MSUD, NKH, serine biosynthesis defect)
healthcare provider caring for an neonate in the NICU

ADSL, adenylosuccinate lyase; GABA, gamma aminobutyric acid; GAMT, guanidinoacetate methyltransferase; GLUT1, glucose transporter type 1; MSUD, maple syrup urine disease; NKH, nonketotic hyperglycinemia.

This list is not exhaustive, but is representative of some of the IEM that may mimic MoCD Type A.

MoCD is clinically similar to HIE, the most common cause of neonatal encephalopathy and seizures1,4

HIE is responsible for 80% of all seizures in the first 2 days of life. A diagnosis of HIE is made presumptively on the basis of neurologic dysfunction in the presence of encephalopathy.4,5

As a result, MoCD may often go undiagnosed due to the difficulty in differentiating it clinically from HIE.6

Computer

Sulfite intoxication should be ruled out with one urine test in the diagnostic workup of neonates presenting with seizures and encephalopathy7,8

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Diagnostic opportunities for MoCD Type A

clipboard used in the clinic

Clinical Evaluation

Signs, symptoms, and family history

  • Neonatal intractable seizures, encephalopathy, and feeding difficulties.7 (See more symptoms of MoCD Type A.)
  • Family history of siblings with similar presentation of symptoms or premature death.2,7,9
brain with overlaid EEG

Neuroimaging

  • Abnormal white matter7
  • Cortical and sub-cortical atrophy7
  • Cyst formation7
  • Abnormal corpus callosum7
  • Abnormal posterior fossa1
blood drop representing metabolic testing

Metabolic tests

Blood

  • High plasma S-sulfocysteine (SSC)7
  • Low, falling, or absent plasma uric acid7,10
  • Low plasma cysteine and homocysteine10,11
  • Occasional metabolic acidosis7

Urine

  • Elevated sulfite and SSC levels7,12
  • Increased taurine, xanthine, and hypoxanthine10,12
  • Low uric acid and cysteine10,11
DNA strand

Rapid genetic testing

  • Positive identification of a mutation in MOCS1.12
  • Identification of other mutations in the sulfite oxidase pathway indicate ISOD or MoCD Types B or C.7

Identification of variants of MOCS1 is the definitive diagnostic proof of MoCD Type A10

Expedited genetic testing is critical for the diagnosis of MoCD Type A.13

Rapid whole genome sequencing and whole exome sequencing are available at some institutions and can provide comprehensive genetic testing with shorter turnaround. MOCS1 genetic testing is also available on some epilepsy and inborn error of metabolism panels.

Genetic screening panels that test for MOCS1 include*:

*Sentynl does not recommend any specific laboratory or screening panel, nor does Sentynl subsidize any test or have any financial interest in the laboratories listed. If you are aware of another laboratory that provides genetic screening panels that test for MOCS1, or would like to have your laboratory included on this list, please email medical_affairs@sentynl.com.

†Behind the Seizure is a registered trademark of Biomarin Pharmaceutical, Inc.

Find more available genetic tests for MOCS1 at the NIH Genetic Testing Registry

Achieving an accurate diagnosis sooner may lead to a better quality of life and treatment outcomes8

MoCD Type A is a devastating, lethal disorder with a typical life expectancy of ~2.4 years without intervention.7

Infants with MoCD Type A who survive past the neonatal period typically experience progressive symptoms, including spasticity, developmental delay, and disability, with death eventually occurring due to secondary complications.7,14

Alert

Because MoCD Type A progresses rapidly, clinical suspicion should be maintained for any neonate who presents with intractable seizures and encephalopathy7

MoCD Type A Diagnostic Brochure from Sentynl Therapeutics, Inc.

Looking for more information about MoCD Type A?

Download this MoCD Type A Diagnostic Brochure now for a guide to distinguishing MoCD Type A from other neonatal seizure disorders.

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diagnostic brochure cover

Looking for more information about MoCD Type A?

Download this MoCD Type A Diagnostic Brochure now for a guide to distinguishing MoCD Type A from other neonatal seizure disorders.

Download

Early diagnosis of MoCD Type A can lead to better patient outcomes and a more hopeful future8

Explore more information about MoCD Type A.

Resources for healthcare professionals

References: 1. Vijayakumar K, Gunny R, Grunewald S, et al. Clinical neuroimaging features and outcome in molybdenum cofactor deficiency. Pediatr Neurol. 2011;45(4):246-252. 2. Mechler K, Mountford W, Hoffmann G, Ries M. Ultra-orphan diseases: a quantitative analysis of the natural history of molybdenum cofactor deficiency. Genet Med. 2015;17(12):965-970. 3. Ferreira CR, van Karnebeek CDM. Inborn errors of metabolism. In: deVries LS, Glass HC, eds. Handbook of Clinical Neurology. 2019;162:449-481. 4. Panayiotopoulos CP. Neonatal seizures and neonatal syndromes. The Epilepsies: Seizures, Syndromes and Management. Bladon Medical Publishing; 2005. 5. Douglas-Escobar M, Weiss MD. Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr. 2015;169(4):397-403. 6. Bayram E, Topcu Y, Karakaya P, et al. Molybdenum cofactor deficiency: review of 12 cases (MoCD and review). Eur J Paediatr Neurol. 2013;17(1):1-6. 7. Spiegel R, Schwahn BC, Squires L, Confer N. Molybdenum cofactor deficiency: a natural history. J Inherit Metab Dis. 2022;45(3):456-46 8. Veldman A, Santamaria-Araujo JA, Sollazzo S, et al. Successful treatment of molybdenum cofactor deficiency type A with cPMP. Pediatrics. 2010;125(5):e1249-e1254. 9. 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. 10. 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. 11. Gropman A. Molybdenum cofactor deficiency (MoCD): a rare genetic disorder in newborns. 2021. Accessed January 9, 2023. https://cdn.mdedge.com/files/s3fs-public/nr_nord_0421_originbio_sponsorship_v12_folio_nocrop_0.pdf. 12. Atwal PS, Scaglia F. Molybdenum cofactor deficiency. Mol Genet Metab. 2016;117(1):1-4. 13. Kingsmore SF, Ramchandar N, James K, et al. Mortality in a neonate with molybdenum cofactor deficiency illustrates the need for a comprehensive rapid precision medicine system. Cold Spring Harb Mol Case Stud. 2020;6(1):a004705. 14. Misko A, Mahtani K, Abbott J, et al. Molybdenum cofactor deficiency. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews® [internet]. University of Washington, Seattle; 1993. Updated December 2, 2021. Accessed January 6, 2023. https://www.ncbi.nlm.nih.gov/books/NBK575630/.

For more information, contact Medical Affairs at Sentynl Therapeutics at 1-888-507-5206