3-methylglutaconic aciduria with cataracts, neurologic involvement and neutropenia

What is 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia?

3-Methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia is a rare genetic disorder characterized by the accumulation of 3-methylglutaconic acid in the urine. This condition is caused by mutations in the CLPB gene on chromosome 11q13 [1][2].

Key Features:

• Increased levels of 3-methylglutaconic acid in the urine
• Neurologic involvement, ranging from mild to severe, including global developmental delay and progressive neurological manifestations [10]
• Neutropenia, which can lead to recurrent severe infections and potentially result in leukemia [10]
• Cataracts may also be present in some individuals [5][9]

Age of Onset:

The symptoms of this condition typically appear in early childhood, with the most severely affected individuals showing features at birth or in infancy [11].

Severity Variance:

The severity of this disorder varies widely among affected individuals, ranging from mild to severe. In some cases, the condition may be associated with neonatal or prenatal onset of neurological disease [15].

References:

[1] Increased amounts of 3-methylglutaconic acid are found in the urine while the bone marrow may contain evidence of arrested granulopoiesis.

[2] This autosomal recessive disorder results from homozygous or compound heterozygous mutations in the CLPB gene (11q13.4).

[5] A rare disorder with characteristics of neurological problems and neutropenia. Onset of symptoms is in early childhood and severity varies widely among affected individuals.

[9] 3-Methylglutaconic aciduria (MGCA7) is an inborn error of metabolism characterized primarily by increased levels of 3-methylglutaconic acid (3-MGA associated with variable neurologic deficits and neutropenia).

[10] A rare organic aciduria characterized by increased urinary excretion of 3-methylglutaconic acid, variably associated with neutropenia and progressive neurologic manifestations.

[11] A rare disorder with characteristics of neurological problems and neutropenia. Onset of symptoms is in early childhood and severity varies widely among affected individuals.

[15] The first description of CLPB-mutated patients described 14 affected individuals with variable phenotype from mild presentation including cataracts and neutropenia but no neurological involvement or infections to severe phenotype associated with neonatal or prenatal onset of neurological disease.

Common Signs and Symptoms

• Decreased muscle tone (hypotonia) [2]
• Movement difficulties [2]
• Seizures [2]
• Smaller than usual head size [2]
• Delayed psychomotor development [3]
• Ataxia [3]
• Dystonia [3]
• Cerebellar and cerebral atrophy, along with brain stem abnormalities (as seen on brain imaging) [3]

Additional Features

• Hypotonia
• Muscle stiffness (spasticity)
• Movement abnormalities [6]
• Cataracts [7]
• Recurrent infections due to neutropenia [7]
• Brain imaging abnormalities [7]
• Global developmental delay [9]
• Neutropenia, which can lead to severe infections and potentially leukemia [9]

Note: The severity and presentation of these symptoms may vary among individuals with 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia.

**Diagnostic Tests for 3-Methylglutaconic Aciduria with Cataracts,

Treatment Options for 3-Methylglutaconic Aciduria

While there are no specific therapeutic options available for the treatment of 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia, supportive therapy and neurologic medications can help manage the symptoms.

• Supportive Therapy: This includes measures to alleviate the symptoms and improve the quality of life. For example, patients may benefit from physical therapy to maintain muscle strength and mobility.
• Neurologic Medications: These can be used to treat the neurologic manifestations of the disease, such as seizures or movement disorders.

Pantothenic Acid Treatment

Interestingly, there have been reports of successful treatment with pantothenic acid in some cases of 3-methylglutaconic aciduria. However, this is not a standard treatment and more research is needed to confirm its efficacy.

• Limited Availability: Pantothenic acid may be available as an experimental treatment for patients with this condition.
• Variable Response: The response to pantothenic acid treatment can vary widely among individuals.

Current Research

Recent studies have highlighted the importance of identifying genetic mutations associated with 3-methylglutaconic aciduria. For example, research has shown that biallelic mutations of CLPB are associated with a syndrome of 3-methylglutaconic aciduria, cataracts, neurologic deterioration, and neutropenia.

• Genetic Testing: Genetic testing can help identify individuals who carry the mutation and may benefit from early intervention.
• Future Research Directions: Further research is needed to develop effective treatments for this condition and improve patient outcomes.

References

• [5] CLPB deficiency is associated with increased levels of a substance called 3-methylglutaconic acid in the urine (3-methylglutaconic aciduria).
• [6] 3-methylglutaconic aciduria with cataracts, neurologic involvement and neutropenia ... 3-methylglutaconic aciduria: successful treatment with pantothenic acid.
• [8] Primary disease symptoms are increased levels of 3-methylglutaconic acid, neurologic deterioration and neutropenia. Other common features include progressive ...
• [9] Apart from supportive therapy and neurologic medications, there are no specific therapeutic options for these affected patients. Neutropenia generally responds ...
• [10] Feb 3, 2022 — Prior studies showed that biallelic mutations of CLPB are associated with a syndrome of 3-methylglutaconic aciduria, cataracts, neurologic ...

Differential Diagnosis

3-Methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia is a rare genetic disorder characterized by increased levels of 3-methylglutaconic acid in the urine (3-methylglutaconic aciduria), congenital or infantile cataracts, neurological problems, and neutropenia. The differential diagnosis for this condition includes:

• Hyperekplexia: A rare genetic disorder characterized by exaggerated startle response, muscle stiffness, and other neurological symptoms [12].
• **Mitochond