molybdenum cofactor deficiency type A

Molybdenum cofactor deficiency (MoCD) Type A is a rare genetic disease that can appear shortly after birth [6]. It is characterized by severe and rapidly progressive neurologic damage, including intractable seizures, which do not improve with treatment [7].

Individuals with MoCD Type A typically present in the first days of life with severe symptoms, such as poor feeding, intractable seizures, and severe psychomotor retardation [1]. The condition is caused by a reduced availability of molybdenum cofactor, which is essential for the activity of certain enzymes involved in the metabolism of sulfur-containing amino acids.

The symptoms of MoCD Type A can be severe and may include uncontrollable muscle movements, weakness, developmental delay, and seizures that do not improve with treatment [5]. In some cases, the symptoms may go away, but this is rare. The condition worsens over time, leading to brain dysfunction (encephalopathy) that can result in death within months of birth [11].

MoCD Type A is a rare condition, affecting approximately 1 in 340,000 to 1 in 410,000 births worldwide [14]. It is caused by biallelic mutations in the MOCS1 gene, which codes for the molybdenum cofactor. The genetic studies have reported more than 100 genetically characterized patients with MoCD Type A.

The diagnosis of MoCD Type A can be made based on a characteristic biochemical profile that includes elevated levels of sulfite and other metabolites [13]. Early diagnosis is essential to provide appropriate treatment and management of the condition.

Overall, Molybdenum cofactor deficiency type A is a severe and rare genetic disease that requires prompt medical attention for proper diagnosis and management.

Molybdenum cofactor deficiency (MoCD) type A is a rare genetic disease that can appear shortly after birth. The signs and symptoms of MoCD type A typically include:

• Trouble feeding: Children with MoCD type A often have difficulty feeding, which can lead to vomiting.
• Seizures: Intractable seizures are one of the first symptoms of MoCD type A, and they can be unresponsive to treatment.
• High-pitched cries: Infants with MoCD type A may exhibit high-pitched crying, which is a characteristic symptom of this condition.
• Exaggerated startle response: Children with MoCD type A may have an exaggerated startle response, which means they may react strongly to sudden noises or movements.

These symptoms can appear within a few hours to a few days after birth, and in some cases, they may be delayed until later infancy. It's essential to note that the severity of these symptoms can vary from one individual to another.

According to various sources [1, 2, 3, 4], MoCD type A is characterized by progressive brain dysfunction and deterioration of the tissue in the brain, which can lead to severe developmental delays and other neurological manifestations. The condition is estimated to affect approximately 1 in 200,000 newborns worldwide.

References: [1] Spiegel R, Schwahn BC, Squires L, Confer N. Molybdenum cofactor deficiency: A natural history. [2] Successful treatment of molybdenum cofactor deficiency type A with cPMP. Pediatrics. 2010;125(5):e1249-e1254. [3] Misko AL, Liang Y, Kohl JB, Eichler F. Delineating the signs and symptoms of sulfite intoxication in MoCD Type A. [4] Spiegel R, Schwahn BC, Squires L, Confer N. Molybdenum cofactor deficiency: a natural history.

Molybdenum cofactor deficiency type A (MoCD Type A) can be diagnosed through various tests, including:

• Biochemical tests: These tests can determine high levels of sulfite, S-sulfocysteine (SSC), xanthine, and hypoxanthine in the urine [7][8]. Low levels of urinary urothion is also virtually diagnostic for MoCD Type A [9].
• Genetic testing: Identification of variants of MOCS1 is the definitive diagnostic proof of MoCD Type A [4][13]. Expedited genetic testing is critical for the diagnosis of MoCD Type A [4].
• Gene panel testing: Doctors often use a gene panel to help with diagnosis, which tests for multiple genetic conditions that have the same or similar symptoms [3].
• Exome-based NextGen sequencing with CNV analysis: This is the favored testing approach, as it allows cost-effective reflexing to PGxome or other exome-based tests [6].

It's worth noting that a combination of clinical examination, neuroimaging findings, urinalysis, and genetic testing are necessary for the diagnosis of MoCD Type A [4][5].

Treatment Options for Molybdenum Cofactor Deficiency Type A

Molybdenum cofactor deficiency (MoCD) type A is a rare and devastating metabolic disease that requires prompt and effective treatment. While there are no cure-all treatments available, recent advancements in medical research have led to the development of a drug therapy that can significantly improve survival rates for babies with MoCD type A.

Fosdenopterin: The First FDA-Approved Treatment

In 2021, the U.S. Food and Drug Administration (FDA) approved Nulibry (fosdenopterin) as the first treatment for reducing the risk of mortality in patients with molybdenum cofactor deficiency type A [11][13][15]. Fosdenopterin is a medication that can help improve survival in babies with MoCD type A by substituting endogenous cyclic pyranopterin monophosphate (cPMP) and allowing the remaining molybdenum cofactor

Molybdenum cofactor deficiency (MoCD) type A has a differential diagnosis that includes several conditions with similar symptoms. Some of these conditions are:

• Glycine encephalopathy: This is a rare genetic disorder characterized by elevated levels of glycine in the blood and urine, leading to severe neurological symptoms.
• Pyridoxamine 5'-phosphate oxidase deficiency: This is another rare genetic disorder that affects the metabolism of vitamin B6, leading to similar symptoms as MoCD type A.
• Vitamin B-6 Dependency Syndromes: These are a group of rare genetic disorders characterized by an abnormal dependence on vitamin B6 for normal metabolic function.

These conditions can present with similar symptoms such as:

• Seizures
• Developmental delay
• Microcephaly (small head size)
• Brain atrophy

However, MoCD type A is caused by a specific change in the MOCS1 gene, which prevents the body from producing a compound called cPMP. This genetic defect can be confirmed through genetic testing.

It's essential to consider these differential diagnoses when evaluating patients with symptoms suggestive of MoCD type A, as early diagnosis and treatment are critical for improving outcomes.

References:

• [8] lists Glycine encephalopathy as a differential diagnosis.
• [8] also lists Pyridoxamine 5'-phosphate oxidase deficiency as a differential diagnosis.
• [8] mentions Vitamin B-6 Dependency Syndromes as another condition to consider in the differential diagnosis of MoCD type A.