Sengers syndrome

Last updated
Senger's syndrome
Other namesCongenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome, Cardiomyopathy and cataract.
Autosomal recessive - en.svg
Autosomal recessive pattern is the inheritance manner of this condition
Symptoms Cataracts, fatigue, muscle weakness, hypotonia, lactic acidosis, and cardiomyopathy. [1]
Usual onsetBirth
Causes Mutations in the AGK and SLC25A4 genes. [2]
FrequencyRare

Sengers syndrome is a rare autosomal recessive mitochondrial disease characterised by congenital cataract, hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise. [3] Biallelic pathogenic mutations in the AGK gene, which encodes the acylglycerol kinase enzyme, cause Sengers syndrome. [2] In addition, heart disease and muscle disease are prevalent, meaning that life expectancy is short for many patients. [1]

Contents

Signs and symptoms

Cataracts often develop shortly after birth or at the time of birth. It may be necessary to have early surgery if they are dense enough to impair vision. Despite this, visual rehabilitation is less than ideal since vision is rarely normal and many children attend special schools for the blind. [1]

Additionally, skeletal muscles and the heart become weak because of this disorder. Common symptoms include fatigue, muscle weakness, and floppiness (hypotonia). It is often seen following exercise that you develop lactic acidosis, which is a medical condition that requires prompt treatment. A thickened heart muscle impairs its pumping ability (hypertrophic cardiomyopathy). The generalized muscle weakness can cause motor development to be delayed, despite normal intelligence. [1]

Genetics

This disease is caused by mutations in AGK or SLC25A4 genes. The AGK gene encodes the mitochondrial acylglycerol kinase which plays a role in the assembly of adenine nucleotide translocator. The SLC25A4 gene encodes the heart and muscle-specific isoform 1 of the mitochondrial adenine nucleotide translocator. [2]

Diagnosis

The diagnosis may be provisionally made on clinical grounds. Ophthalmologists, neurologists, cardiologists, and pediatricians are some of the specialists who can make the diagnosis. Because of the widespread impact of the disease, it is most likely to be a collaborative effort. Acute lactic acidosis and heart disease are the greatest threats to life and must be treated promptly. Yet, more than half of newborns die before they reach their second birthday, and some live a decade or more. In terms of severity, there is a considerable range. [1] Further diagnostic tests include serum and urine analysis for lactic acid, a chest X-ray (or cardiac CT or MRI) and echocardiography. Biopsies from cardiac and skeletal muscle will show the presence of lipid and glycogen. Testing for mitochondrial abnormalities, ANT deficiency, and decreases of respiratory chain complexes I and IV can also be done.

Differential diagnosis

Treatment

Surgery for cataracts may be needed. Medical treatment for cardiac failure will be required. Treatment is otherwise supportive.

Prognosis

About half the patients die within the first year of life. Because of its rarity, the prognosis for the chronic form is not well established but survival into adulthood has been reported.

Epidemiology

Sengers syndrome is a rare disorder. About 40 cases have been reported worldwide. [4]

History

This condition was first described in 1975. [5]

Related Research Articles

<span class="mw-page-title-main">Leigh syndrome</span> Metabolic disease

Leigh syndrome is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951. Normal levels of thiamine, thiamine monophosphate, and thiamine diphosphate are commonly found, but there is a reduced or absent level of thiamine triphosphate. This is thought to be caused by a blockage in the enzyme thiamine-diphosphate kinase, and therefore treatment in some patients would be to take thiamine triphosphate daily. While the majority of patients typically exhibit symptoms between the ages of 3 and 12 months, instances of adult onset have also been documented.

<span class="mw-page-title-main">Exercise intolerance</span> Inability to perform physical exercise at normal levels

Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe post-exercise pain, fatigue, nausea, vomiting or other negative effects. Exercise intolerance is not a disease or syndrome in and of itself, but can result from various disorders.

<span class="mw-page-title-main">Mitochondrial myopathy</span> Muscle disorders caused by mitochondrial dysfunction

Mitochondrial myopathies are types of myopathies associated with mitochondrial disease. Adenosine triphosphate (ATP), the chemical used to provide energy for the cell, cannot be produced sufficiently by oxidative phosphorylation when the mitochondrion is either damaged or missing necessary enzymes or transport proteins. With ATP production deficient in mitochondria, there is an over-reliance on anaerobic glycolysis which leads to lactic acidosis either at rest or exercise-induced.

Mitochondrially encoded tRNA leucine 1 (UUA/G) also known as MT-TL1 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL1 gene.

Mitochondrially encoded tRNA histidine, also known as MT-TH, is a transfer RNA which, in humans, is encoded by the mitochondrial MT-TH gene.

<span class="mw-page-title-main">Phosphate carrier protein, mitochondrial</span>

Phosphate carrier protein, mitochondrial is a protein that in humans is encoded by the SLC25A3 gene. The encoded protein is a transmembrane protein located in the mitochondrial inner membrane and catalyzes the transport of phosphate ions across it for the purpose of oxidative phosphorylation. There are two significant isoforms of this gene expressed in human cells, which differ slightly in structure and function. Mutations in this gene can cause mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation symptomized by lactic acidosis, neonatal hypotonia, hypertrophic cardiomyopathy, and death within the first year of life.

<span class="mw-page-title-main">AGK (gene)</span> Protein-coding gene in the species Homo sapiens

The human gene AGK encodes the enzyme mitochondrial acylglycerol kinase.

<span class="mw-page-title-main">ISCU</span> Mammalian protein found in Homo sapiens

Iron-sulfur cluster assembly enzyme ISCU, mitochondrial is a protein that in humans is encoded by the ISCU gene. It encodes an iron-sulfur (Fe-S) cluster scaffold protein involved in [2Fe-2S] and [4Fe-4S] cluster synthesis and maturation. A deficiency of ISCU is associated with a mitochondrial myopathy with lifelong exercise intolerance where only minor exertion causes tachycardia, shortness of breath, muscle weakness and myalgia.

Mitochondrially encoded tRNA valine also known as MT-TV is a transfer RNA which in humans is encoded by the mitochondrial MT-TV gene.

Danon disease is a metabolic disorder. Danon disease is an X-linked lysosomal and glycogen storage disorder associated with hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability. It is inherited in an X-linked dominant pattern.

Mitochondrially encoded tRNA aspartic acid also known as MT-TD is a transfer RNA which in humans is encoded by the mitochondrial MT-TD gene.

Mitochondrially encoded tRNA glutamic acid also known as MT-TE is a transfer RNA which in humans is encoded by the mitochondrial MT-TE gene. MT-TE is a small 69 nucleotide RNA that transfers the amino acid glutamic acid to a growing polypeptide chain at the ribosome site of protein synthesis during translation.

Mitochondrially encoded tRNA phenylalanine also known as MT-TF is a transfer RNA which in humans is encoded by the mitochondrial MT-TF gene.

Mitochondrially encoded tRNA glycine also known as MT-TG is a transfer RNA which in humans is encoded by the mitochondrial MT-TG gene.

Mitochondrially encoded tRNA isoleucine also known as MT-TI is a transfer RNA which in humans is encoded by the mitochondrial MT-TI gene.

Mitochondrially encoded tRNA lysine also known as MT-TK is a transfer RNA which in humans is encoded by the mitochondrial MT-TK gene.

Mitochondrially encoded tRNA leucine 2 (CUN) also known as MT-TL2 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL2 gene.

Mitochondrially encoded tRNA arginine also known as MT-TR is a transfer RNA which in humans is encoded by the mitochondrial MT-TR gene.

Mitochondrially encoded tRNA threonine also known as MT-TT is a transfer RNA which in humans is encoded by the mitochondrial MT-TT gene.

<span class="mw-page-title-main">Marinesco–Sjögren syndrome</span> Medical condition

Marinesco–Sjögren syndrome (MSS), sometimes spelled Marinescu–Sjögren syndrome, is a rare autosomal recessive disorder.

References

  1. 1 2 3 4 5 "Sengers Syndrome | Hereditary Ocular Diseases".
  2. 1 2 3 Wu, Chen-Han Wilfred; Caha, Martin; Smoot, Leslie; Harris, David J.; Roberts, Amy E.; Sacharow, Stephanie; Bodamer, Olaf (July 2023). "Sengers syndrome and AGK-related disorders — Minireview of phenotypic variability and clinical outcomes in molecularly confirmed cases". Molecular Genetics and Metabolism. 139 (3): 107626. doi:10.1016/j.ymgme.2023.107626. ISSN   1096-7206. PMID   37354892.
  3. ↑ "Orphanet: Sengers syndrome". orpha.net. Retrieved 2023-08-18.
  4. ↑ "Entry #212350 – SENGERS SYNDROME — OMIM". omim.org. Retrieved 2023-08-19.
  5. ↑ Sengers RCA, ter Haar, BGA, Trijbels JMF, Willems JL, Daniels O, Stadhouders AM (1975) Congenital cataract and mitochondrial myopathy of skeletal and heart muscle associated with lactic acidosis after exercise. J Pediat 86: 873–880
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.