molybdenum cofactor deficiency type C

Molybdenum cofactor deficiency type C, also known as GPHN-related MoCD, is a rare and severe form of the disorder.

Causes and Genetics This condition is caused by mutations in the GPHN gene, which is responsible for producing a protein necessary for the production of molybdenum cofactor. The GPHN gene is located on chromosome 14q23.

Clinical Features Individuals with MoCD type C typically present in infancy with severe symptoms, including:

• Poor feeding
• Seizures (intractable seizures)
• Severe psychomotor retardation

These symptoms can lead to death in early childhood if left untreated. The condition is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder.

References

• [1] Molybdenum cofactor deficiency type C is caused by homozygous mutation in the GEPH gene (GPHN; 603930) on chromosome 14q23.
• [3] Individuals with early-onset MoCD typically present in the first days of life with severe symptoms, including poor feeding and seizures.
• [5] Molybdenum cofactor deficiency, type C is an autosomal recessive metabolic disorder resulting in the loss of molybdoenzyme activities.
• [13] Type C is caused by a problem in the GPHN gene; These genes are needed to produce different proteins which your body uses to make a molecule called molybdenum cofactor.

Molybdenum cofactor deficiency (MoCD) type C is a rare genetic disorder that affects the body's ability to break down certain compounds, leading to severe health consequences.

Common signs and symptoms:

• Frequent, intractable seizures [5]
• Abnormal muscle tone (increased or decreased)
• Difficulty feeding
• Extreme fussiness
• Exaggerated startle response

These symptoms often appear at birth or shortly after, and can be life-threatening if left untreated. In addition to these specific signs, individuals with MoCD type C may also experience:

• Severe developmental delay: Children with MoCD type C often have significant delays in reaching developmental milestones, such as sitting, standing, and walking [6].
• Brain abnormalities: The condition can lead to severe brain damage, including atrophy and degeneration of brain tissue [8].
• Vision problems: Some individuals may experience visual dysfunction, including lens dislocation [9].

It's essential to note that these symptoms can vary in severity and presentation from one individual to another. If you suspect a child or adult has MoCD type C, it is crucial to seek immediate medical attention.

References: [5] SIGNS AND SYMPTOMS · Frequent, intractable seizures · Abnormal muscle tone (increased or decreased) · Difficulty feeding · Extreme fussiness · Exaggerated startle ... [6] by M Nagappa · 2015 · Cited by 23 — Molybdenum cofactor deficiency (MoCD) is a rare inherited metabolic disorder characterized by neonatal onset intractable seizures, severe psychomotor ... [8] by PS Atwal · 2016 · Cited by 113 — It is characterized by neonatal presentation of intractable seizures, feeding difficulties, severe developmental delay, microcephaly with brain atrophy and ... [9] Feb 11, 2019 — Most survivors have some combination of seizures, feeding difficulties, mental retardation, visual dysfunction with lens dislocation, and ...

Molybdenum cofactor deficiency (MoCD) type C is a rare and severe form of the condition, characterized by early-onset disease and frequent seizures that don't improve with anti-seizure medication [2]. The diagnosis of MoCD type C can be established through various diagnostic tests.

Urine or Blood Test: A urine or blood test (biochemical test) can confirm a diagnosis of MoCD type C. This test measures the levels of certain chemicals, such as sulfite, S-sulfocysteine, xanthine, and hypoxanthine in the urine [4]. Elevated levels of these substances are indicative of MoCD type C.

S-sulfocysteine Detection: S-sulfocysteine can be detected by a urine dipstick test or measured by mass spectrometry. This test is crucial for diagnosing MoCD type C, as it helps identify the presence of this specific compound in the urine [6].

Complete Laboratory Workup: A complete laboratory workup for diagnosis includes plasma amino acids, serum uric acid, urine amino acids, and total sulfite levels. These tests help confirm the diagnosis of MoCD type C by identifying the characteristic biochemical profile associated with this condition [7].

Urinary Urothion Levels: Low urinary urothion levels are virtually diagnostic for molybdenum cofactor deficiency (except in cases where there is a specific mutation) [8]. This test helps confirm the diagnosis of MoCD type C by identifying the presence or absence of this compound in the urine.

Targeted Mutation Analysis: Targeted mutation analysis, including genetic testing of the GPHN gene, can also be used to diagnose MoCD type C. This involves analyzing specific mutations associated with the condition [9].

In summary, the diagnostic tests for molybdenum cofactor deficiency type C include:

• Urine or blood test (biochemical test)
• S-sulfocysteine detection
• Complete laboratory workup
• Urinary urothion levels
• Targeted mutation analysis

These tests help confirm the diagnosis of MoCD type C by identifying the characteristic biochemical profile and genetic mutations associated with this condition.

Molybdenum cofactor deficiency (MoCD) type C is a rare and severe genetic metabolic disorder that affects the body's ability to form an essential cofactor called molybdenum cofactor. This condition is caused by a genetic deficiency of cyclic pyranopterin monophosphate (cPMP), which results in the inability of the body to produce this critical cofactor.

Unfortunately, there is no specific drug treatment available for MoCD type C. The first causal treatment, fosdenopterin, was approved by the FDA in 2021 specifically for treating MoCD type A, not type C [8][9]. This treatment works by substituting endogenous cPMP with fosdenopterin, which is effective at reducing mortality risk in patients with MoCD type A [6][7].

However, for MoCD type C, the current treatment options are limited and primarily focused on managing symptoms and supporting overall health. Research into new treatments and therapies for MoCD type C is ongoing, but no specific drug treatment has been approved or widely adopted for this condition.

It's worth noting that some studies have explored the potential use of cPMP substitution in treating severe MoCD type A, which may also be relevant to MoCD type C [13][14]. However, more research is needed to determine the efficacy and safety of such treatments for MoCD type C specifically.

Molybdenum cofactor deficiency (MoCD) type C is a rare and severe form of the disorder, and its differential diagnosis can be challenging due to its similarity with other conditions. However, based on the available information, here are some key points to consider:

• Hypoxic-Ischemic Encephalopathy (HIE): MoCD type C can be difficult to distinguish from HIE, especially in the early stages of diagnosis. Both conditions present with similar clinical features such as seizures, developmental delay, and brain atrophy on MRI scans [4].
• Glycine Encephalopathy: This is another rare metabolic disorder that can present with similar symptoms to MoCD type C, including seizures, developmental delay, and encephalopathy [8].
• Pyridoxamine 5'-phosphate oxidase deficiency: This is a rare genetic disorder that affects the metabolism of vitamin B6 and can present with similar symptoms to MoCD type C, including seizures, developmental delay, and encephalopathy [8].
• Vitamin B-6 Dependency Syndromes: These are a group of rare disorders that affect the metabolism of vitamin B6 and can present with similar symptoms to MoCD type C, including seizures, developmental delay, and encephalopathy [8].

It's essential to note that the differential diagnosis of MoCD type C requires a comprehensive evaluation of clinical features, laboratory results, and imaging studies. A detailed biochemical profile is also crucial in establishing an accurate diagnosis.

References:

[4] Nagappa M (2015) - Brain MRI should be used judiciously to distinguish MoCD from HIE, with is a close differential diagnosis. [8] Various sources [8] - Differential Diagnoses: Glycine encephalopathy, Pyridoxamine 5'-phosphate oxidase deficiency, Vitamin B-6 Dependency Syndromes.