Sengers syndrome

Sengers syndrome, also known as Congenital Cataract-Hypertrophic Cardiomyopathy-Mitochondrial Myopathy (CCM), is a rare autosomal recessive mitochondrial disorder.

Characteristics of the Syndrome:

• Congenital cataracts: A clouding of the lens in the eye that is present at birth.
• Hypertrophic cardiomyopathy: A condition where the heart muscle becomes thickened, leading to progressive and potentially life-threatening heart failure.
• Mitochondrial myopathy: A disease affecting the muscles due to mitochondrial dysfunction.

Other symptoms may include:

• Muscle weakness
• Lactic acidosis (elevated levels of lactic acid in the blood) following exertion

Prognosis and Treatment: Unfortunately, there is no definitive therapy for Sengers syndrome. The prognosis is variable, and the cause of death is typically related to heart failure due to hypertrophic cardiomyopathy.

References:

• [1] Sengers syndrome is an autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, ... (Source: 1)
• [2] Sengers syndrome is a rare autosomal recessive mitochondrial disease characterised by congenital cataract, hypertrophic cardiomyopathy, muscle weakness and ... (Source: 2)
• [3] The AGK gene mutation causes Sengers syndrome. (Source: 3)
• [4] Congenital cataract – hypertrophic cardiomyopathy – mitochrondrial myopathy (CCM) is a mitochondrial disease characterized by cataracts, ... (Source: 4)
• [5] The current study describes an autosomal recessive disorder with features of cardiomyopathy, skeletal myopathy, congenital bilateral cataracts, and lactic acidosis following exertion. (Source: 8)

Sengers syndrome is a rare autosomal recessive mitochondrial disease characterized by several distinct signs and symptoms.

Common Signs and Symptoms:

• Congenital cataract (94.7%)[5]
• Hypertrophic cardiomyopathy (65.8%)[5]
• Lactic acidemia (71.1%)[5]
• Myopathy (65.8%)[5]

Other Possible Signs and Symptoms:

• Nystagmus
• Strabismus
• Hypotonia
• Hyporeflexia
• Delayed motor development
• Marked lactic acidemia with even limited muscular activity[13]

It's worth noting that no single symptom or sign is present in all patients, and the clinical spectrum of Sengers syndrome can vary significantly between individuals [12].

References: [5] - Cataracts were the most common clinical manifestation (94.7%), followed by hypertrophic cardiomyopathy (65.8%), lactic acidemia (71.1%), and myopathy (65.8%). [12] - After comparing the reported clinical spectrum of Sengers syndrome, it was observed that no single symptom or sign was present in all patients. [13] - Marked lactic acidemia occurs with even limited muscular activity.

Sengers syndrome, also known as mitochondrial myopathy, lactic acidosis, and cataract (MLAC), is a rare autosomal recessive mitochondrial disease characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Given the clinical manifestations of Sengers syndrome, diagnostic tests can be employed to confirm the diagnosis.

Clinical Molecular Genetics Test: This test involves sequence analysis of the entire coding region, bi-directional Sanger Sequence Analysis, or other molecular genetic techniques to identify pathogenic mutations in the AGK gene (1, 3). The AGK gene encodes the acylglycerol kinase enzyme, and biallelic pathogenic mutations in this gene have been associated with Sengers syndrome (4).

Sequence analysis of the entire coding region: This test is used to identify mutations in the AGK gene that cause Sengers syndrome. It involves analyzing the DNA sequence of the entire coding region of the AGK gene to detect any mutations or variations that may be associated with the disease.

Bi-directional Sanger Sequence Analysis: This test is similar to the above, but it involves analyzing the DNA sequence in both directions (forward and reverse) to ensure that no mutations are missed.

Deletion/duplication analysis: This test is used to detect deletions or duplications of genetic material in the AGK gene that may be associated with Sengers syndrome. It involves analyzing the DNA sequence to identify any deletions or duplications that may have occurred.

These diagnostic tests can help confirm a diagnosis of Sengers syndrome and provide valuable information for clinical management and family planning.

References: [1] Mayr et al. (2012) - Sengers syndrome is clinically characterized by exercise intolerance, hypertrophic cardiomyopathy, skeletal myopathy, and congenital cataracts. [3] Clinical Molecular Genetics test for Sengers syndrome and using Sequence analysis of the entire coding region, Bi-directional Sanger Sequence Analysis ... [4] October 22, 2024 - Sengers syndrome is a rare autosomal recessive mitochondrial disease characterised by congenital cataract, hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise. [9] March 30, 2016 - Clinical Molecular Genetics test for Cataract and cardiomyopathy and using Deletion/duplication analysis, Comparative Genomic Hybridization offered by PreventionGenetics.

Current Status of Drug Treatment for Sengers Syndrome

Sengers syndrome, a rare mitochondrial disorder, currently lacks a definitive therapy. According to recent investigations and the small population with this disease, there is no specific treatment strategy available [10][13]. The standard treatment regimen consists of cataract surgery and medical management of cardiomyopathy, but it does not address the underlying cause of the condition [6].

Elamipretide as a Potential Treatment Option

However, elamipretide has been explored in patients with mitochondrial disorders, including Sengers syndrome. A study described its use in patients aged <12 years, providing dosing parameters for this age group [3]. While this may offer some hope for treatment, it is essential to note that the effectiveness of elamipretide in Sengers syndrome specifically has not been established.

No Known Treatment for Cardiac Failure

The primary cause of death in patients with Sengers syndrome is cardiac failure due to hypertrophic cardiomyopathy. Unfortunately, there is no known treatment for this aspect of the condition [2][5]. Genetic counseling and screening for AGK mutations are necessary to identify carriers in at-risk families.

Cataract Surgery as a Palliative Measure

While cataract surgery can add value to the lives of individuals with Sengers syndrome by improving their quality of life, it does not address the underlying disease process [6].

In summary, there is currently no definitive treatment for Sengers syndrome. Medical management and palliative care measures are available, but they do not address the root cause of the condition.

References: [1] Context result 2 [3] Context result 3 [5] Context result 5 [6] Context result 6 [10] Context result 10 [13] Context result 13

Sengers syndrome, a rare autosomal recessive mitochondrial disease, requires careful consideration of differential diagnoses to ensure accurate diagnosis and treatment.

Key Differential Diagnoses:

• Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome [13][14]
• Other mitochondrial diseases, such as Kearns-Sayre syndrome, MERRF syndrome, and NARP syndrome
• Congenital heart defects, such as hypertrophic cardiomyopathy
• Metabolic disorders, such as Pompe disease and McArdle disease

Distinguishing Features:

• Sengers syndrome is characterized by the triad of hypertrophic cardiomyopathy, cataracts, and lactic acidosis [12][12]
• The presence of congenital cataracts is a key feature that distinguishes Sengers syndrome from other mitochondrial diseases [3][8]
• Lactic acidosis is a common feature in Sengers syndrome, but it can also be present in other conditions, such as MELAS syndrome [13]

Importance of Differential Diagnosis:

• Accurate diagnosis of Sengers syndrome requires consideration of differential diagnoses to rule out other mitochondrial diseases and metabolic disorders
• Failure to consider differential diagnoses can lead to misdiagnosis and inappropriate treatment [14]

In conclusion, Sengers syndrome is a rare autosomal recessive mitochondrial disease that requires careful consideration of differential diagnoses to ensure accurate diagnosis and treatment. The presence of congenital cataracts and lactic acidosis are key features that distinguish Sengers syndrome from other conditions.

References:

[1] Sengers et al. (1975) - Original description of Sengers syndrome [2] Mayr et al. (2012) - Mapping of the causative gene to AGK on chromosome 7q34 [3] Sengers syndrome is an autosomal recessive condition characterized by congenital cataract, hypertrophic cardiomyopathy, skeletal myopathy and lactic acidosis. [8] Mutation of the Acylglycerol Kinase (AGK) gene on 7q34. [12] Sengers syndrome (OMIM# 212350) is an autosomal recessive mitochondriopathy, which was first described by Sengers et al. in 1975 as a unique combination of hypertrophic cardiomyopathy with cataracts, associated with excessive exercise-induced lactic acidosis, with or without skeletal myopathy [1].In 2012, Mayr et al. mapped the causative gene to AGK on chromosome 7q34 [2]. [13] Sengers syndrome was first considered in this patient with history of hypertrophic cardiomyopathy, mitochondrial myopathy, hyperlactatemia, and bilateral cataract. [14] This case highlights the importance of maintaining a wide differential diagnosis for congenital lactic acidosis despite seemingly obvious etiologies [9].