Syndromic congenital sideroblastic anaemias (CSA) are a heterogeneous group of anaemic syndromes characterized by the presence of anaemia together with other clinical syndromes. These different entities are due to mutations of nuclear genes or mutations in the mitochondrial DNA. Kearns-Sayre’s syndrome (KSS) is a mitochondrial inherited disease due to deletions of the mitochondrial DNA.
Syndromic CSA is a heterogeneous group of rare genetic disease causes by mutations in different nuclear genes or in the mitochondrial DNA. Kearns-Sayre’s syndrome (KSS) is a neuromuscular disease characterized by an onset before the age of 20 years, ophthalmoplegia, ptosis and pigmentary retinitis. It is caused by deletions of large portions of mitochondrial DNA. Few cases of Pearson syndrome (see this term) have progressed into Kearns-Sayre syndrome. More than 200 cases have been published and the prevalence is estimated between 1 and 3/100 000.
Kearns-Sayre’s syndrome often starts with ocular symptoms, followed by the progressive occurrence of several other signs. The most frequently associated symptoms include deafness, heart involvement (cardiomyopathy, cardiac conduction defect), cerebral involvement (ataxia, high cerebrospinal fluid protein content, intellectual deficit), skeletal muscle myopathy, intestinal disorders, hormonal deficit (hypoparathyroidism, diabetes), and renal failure. The disease progresses slowly, with new symptoms appearing and previous symptoms slowly worsening. Infantile macrocytic sideroblastic anaemia is present in patients with Pearson’s syndrome that survive the pancytopenic crisis and later on develop KSS.
Treatment of the various symptoms is supportive. The prognosis essentially depends on the number of organs involved. The disease progresses slowly over decades. One child with incomplete form of KSS and a profound cerebrospinal fluid folate deficiency has been treated with oral folinic acid with a good clinical improvement (Pineda M, et al., 2006).
Most cases of Kearns-Sayre’s syndrome are sporadic and cases with maternal mitochondrial transmission have been described. Mitochondria contain their own distinct genome; mutations in mitochondrial DNA (mtDNA) or genes are maternally inherited since ova contain mitochondria, whereas sperm contain very few, if any, mitochondria. The father of an affected person is not at risk of having the disease-causing mtDNA mutation. The mother of an affected person usually has the mtDNA mutations and may or may not have symptoms. A man with an mtDNA mutation cannot transmit the mutation to any of his offspring. A woman (affected or unaffected) transmits the mutation to all of her childrens that can be affected or not depending on the quantity of mitochondria with the mutated DNA that they have. Ask for genetic counselling to get a complete explanation.