Molybdenum cofactor deficiency (MoCD): a rare genetic disorder in newborns

MoCD is an ultra-rare, life-threatening genetic disorder that can appear shortly after birth and progresses very quickly.1,2 It is caused by genetic mutations that affect normal metabolism in the human body, causing toxic sulfite to accumulate in the brain. This also occurs in isolated sulfite oxidase deficiency (ISOD), a genetic disorder that presents like MoCD.1-5 Progression is rapid with a high infant mortality rate; median survival age is 3 years. Those who survive beyond the first few months without treatment often have severe developmental delays, emphasizing the urgency to diagnose and treat MoCD as early as possible.1,5,6

MoCD is often confused with other causes of neonatal seizures

MoCD may be confused with other more common seizure disorders and hypoxic injury such as hypoxic-ischemic encephalopathy (HIE), which can cause early seizures.5,7 MoCD may be missed in children who present with similar symptoms.

  • If HIE is presumed responsible for early seizures, diagnostic tests that identify MoCD as the true cause may not be performed quickly enough and precious time may be lost5,7

The symptoms of MoCD1-3

Watch for these symptoms in a newborn, which could mean MoCD:

  • Intractable seizures (seizures that are hard to control)
    • These seizures can occur within hours to days after birth
  • Feeding difficulties
  • High-pitched cries
  • Exaggerated startle reactions
  • Increased tightness of muscle tone (hypertonia)
  • Reduced muscle tone (hypotonia)

Mechanism/Pathway of MoCD

There are 3 different types of MoCD: A, B, and C. Type A, caused by a mutation in the MOCS1 gene, is the most common.1,2 The MOCS1 mutation disrupts the production of a substance called cyclic pyranopterin monophosphate (cPMP), which is needed to produce molybdenum cofactor (MoCo).1-4 MoCo is essential for the normal functioning of several important enzymes, including sulfite oxidase (SOX). Without MoCo, the function of SOX is impaired and the body cannot break down sulfite, a highly toxic substance that can accumulate in the brain. The buildup of toxic sulfite (also known as sulfite intoxication) and a substance that occurs secondary to sulfites called S-sulfocysteine (SSC) leads to rapid and progressive neurological damage.1,2,4,5

MoCo biosynthesis in a healthy child compared to a child with MoCD Type A

References: 
  1. Mechler K et al. Genet Med. 2015;17(12):965-970.
  2. Veldman A et al. Pediatrics. 2010;125(5):e1249-e1254.
  3. Schwahn BC et al. Lancet. 2015;386(10007):1955-1963.
  4. National Institutes of Health. Isolated sulfite oxidase deficiency. https://ghr.nlm.nih.gov/condition/isolated-sulfite-oxidase-deficiency#genes. Accessed April 8, 2020.
  5. Durmaz MS et al. Radiol Case Rep. 2018;13(3):592-595.
  6. Atwal PS et al. Mol Genet Metab. 2016;117(1):1-4.
  7. Vasudevan C et al. Semin Fetal Neonatal Med. 2013;18(4):185-191.
  8. Reiss J et al. Hum Mutat. 2011;32(1):10-18.

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