AGK

Sengers Syndrome

Clinical Characteristics
Ocular Features: 

This is a mitochondrial DNA depletion syndrome in which congenital cataracts are the hallmark ocular feature.  The bilateral lens opacification is usually total at birth or within the first few weeks of life as manifested by leucocoria. Lens extraction is necessary within the first 6 months of life but visual rehabilitation is nearly always compromised postoperatively by nystagmus and strabismus.  In one series only one eye recovered to 20/40 but the average postoperative acuity was in the range of 20/200 and virtually all students require special education in schools for the visually impaired.  Axial myopia is common with most patients having myopic fundus changes and requiring less than +10 diopters of aphakic correction.  Pale optic disks and a pigmentary retinopathy were noted among 8 of 18 eyes in one series.  Mild and inconsistent dyschromatopsia has been reported in a few patients.  The ERG sometimes shows diminished rod and cone function.

Systemic Features: 

Hypertrophic cardiomyopathy is often diagnosed within a fews days after birth but 40% may escape detection until the second or third decade of life.  It is usually progressive and often fatal in the neonatal period.  Myopathy involves both cardiac and skeletal muscles.  Generalized hypotonia, exercise intolerance, and delayed motor development are important features in the majority of patients.  Metabolic lactic acidosis occurs with relatively minimal excercise.  Skeletal muscle biopsies show ragged-red fibers with combined deficiencies of mitochondrial complexes I, III, and IV along with severe depletion of mtDNA.  Increased urine levels of 3-methylglutaconic have been reported.

The central nervous system is usually not involved and mental development is normal if lactic acidosis is controlled.  However, several children with mental retardation have been reported.

Genetics

Homozygous or compound heterozygous mutations in AGK (7p34), a lipid metabolism gene, are responsible for this condition.  There is considerable variation in the severeity of the phenotypic features but no ocular or cardiac disease has been found in heterozygotes. 

The same gene was found to be mutated in an autosomal recessive congenital cataract (614691) in a single reported sibship. Thorough systemic evaluation found no evidence of cardiac and skeletal muscle disease.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Surgical removal of cataracts may be indicated.

References
Article Title: 

Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome

Mayr JA, Haack TB, Graf E, Zimmermann FA, Wieland T, Haberberger B, Superti-Furga A, Kirschner J, Steinmann B, Baumgartner MR, Moroni I, Lamantea E, Zeviani M, Rodenburg RJ, Smeitink J, Strom TM, Meitinger T, Sperl W, Prokisch H. Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome. Am J Hum Genet. 2012 Feb 10;90(2):314-20.

PubMed ID: 
22284826

Cataracts, Congenital, Autosomal Recessive 5

Clinical Characteristics
Ocular Features: 

This type of autosomal recessive congenital cataract has been identified in a single consanguineous family.  The lens opacities (not further characterized) are the only ocular abnormalities found in two boys and 1 girl belonging to a single sibship born to parent who were second cousins.  Extensive systemic evaluations found no evidence of clinical disease as found in Sengers syndrome (212350).

Systemic Features: 

There are no systemic abnormalities.

Genetics

This type of cataract results from homozygous mutations in AGK (7q33-q36.1), a lipid metabolism gene.  Sengers syndrome (212350) is also caused by mutations in the same gene.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Cataract surgery may be indicated if the opacities are visually significant..

References
Article Title: 
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