1. Biochemical abnormalities in Pearson syndrome.
In this case study, four patients with Pearson's syndrome were studied. Out of the four, three failed to thrive in spite of having a normal development. The syndrome affected their bone marrow but three patients showed spontaneous improvement. Out of the four patients, one exhibited acute pancreatitis, one displayed an unusual 3‐hydroxyisobutyric aciduria, and although all of them had renal Fanconi syndrome, it was symptomatic in only one of them. Low levels of plasma citrulline and arginine were detected through biochemical analysis, even though the ammonia levels were low-normal. It was observed through a regression analysis that all the intermediates of the urea cycle had a significant correlation between them except ornithine and citrulline. This indicated that in patients with Pearson's syndrome, the reaction that converts ornithine to citrulline, catalyzed by ornithine transcarbamylase might not be effective. Thus ammonia and carbamyl phosphate could be diverted from urea cycle to synthesis of nucleotides.
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Reference: Beatrice Letizia Crippa, Eyby Leon, Amy Calhoun, Amy Lowichik. Marzia Pasquali, & Nicola Longo (2015). Biochemical abnormalities in Pearson syndrome. Am J Med Genet Part A. 167A:621–628.
2. Allogeneic bone marrow transplantation for Pearson's syndrome.
A four-month-old female child with Pearson's syndrome who had macrocytic anemia and mild hyperlactacidemia underwent hematopoietic stem cell transplantation (UD-HSCT) from two unrelated donors. In the next five years, she developed thrombocytopenia and neutropenia with recurrent bacterial infections. This was the first case which lead to the disappearance of hematological manifestations completely after a successful allogeneic HSCT. There were, however, some complications, as the patient had a bacterial infection and the drugs used to treat it led to renal and tubular damage. Thus, allogeneic HSCT is a possible therapeutic strategy for hematological disorders with patients that do not have multi-system involvement in Pearson's syndrome, although, careful pulmonary and neurological screening should be done before the transplant and in critical conditions, a close follow-up is required.
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Reference: M Faraci, D Cuzzubbo, C Micalizzi, E Lanino, G Morreale, S Dallorso, E Castagnola, M C Schiaffino, C Bruno, A Rossi, G Dini, & B Cappelli (2007). Bone Marrow Transplantation volume 39, pages 563–565, Nature Publishing Group.
3. Pearson's syndrome without marrow involvement.
A six-month-old female child who had Pearson's syndrome showed no bone marrow involvement but had pancreatic exocrine insufficiency. She initially had recurrent episodes of diarrhea and began to lose weight rapidly. Molecular analysis of her mtDNA revealed that there was a heteroplasmic 5kb deletion in muscle and leukocytes that was associated with the loss of BamH1 and SnaB1 restriction sites but not the PvuII site. A similar portion of mtDNA was deleted in both muscle and leukocytes. This case exhibits that Pearson's syndrome can cause a range of diseases in the infant and childhood stages and are not limited to only a set of diseases. Even though the patient does not display anemia, the unexplained pancreatic exocrine insufficiency may be linked to mtDNA rearrangements. The patient exhibited raised lactate concentrations, hepatic and renal tubular abnormalities which pointed to a possibility of Pearson's syndrome. Furthermore, the blood lactate concentrations in the patient were sometimes only slightly above the normal limit. Thus, a low threshold should be kept for searching mtDNA rearrangements, which may be present even if the patient does not have any hematological abnormalities.
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Reference: Morris AAM, Lamont PJ, & Clayton PT (1997). Pearson’s syndrome without marrow involvement: Archives of Disease in Childhood;77:56-57.
4. Mitochondrial DNA deletion in a child with megaloblastic anemia and recurrent encephalopathy.
A three-and-half-year-old boy who had megaloblastic anemia also had repeated incidents of critical lactic acidosis and coma. He had sepsis when he was four, and then eventually died. The postmortem report did not show abnormality in any of his tissues, hence biochemical analysis of muscle was conducted which revealed reduced activities of all respiratory chain enzymes with the exception of complex II. A deficiency of cytochrome c oxidase enzyme was detected by muscle histochemistry. Southern blot analysis was conducted of mtDNA from muscle, liver, and blood, which revealed a heteroplasmic single mitochondrial DNA deletion of 2.4 kb that was responsible for the deletion cytochrome c oxidase I and II genes and the transfer ribonucleic acid genes for serine and aspartic acid. Generally, these single large-scale deletions in mtDNA are related to Pearson's syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. The patient's condition was found unusual and was likely to be an overlap between Pearson's syndrome and Kearns-Sayre syndrome.
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Reference: Akman, C. I., Sue, C. M., Shanske, S., Tanji, K., Bonilla, E., Ojaimi, J., & DiMauro, S. (2004). Mitochondrial DNA Deletion in a Child Mitochondrial DNA Deletion in a Child With Megaloblastic Anemia and Recurrent Encephalopathy: Journal of Child Neurology, 19(4), 258–261.
5. Microvesicular steatosis, hemosiderosis and rapid development of liver cirrhosis in a patient with Pearson's syndrome.
The patient was a male infant who had typical ringed sideroblasts that were observed in a bone marrow smear and a deletion of 7436bp mtDNA that indicated he had Pearson's syndrome. His liver failed and he died within three months of birth. Histopathological analysis of his liver was done which showed complete cirrhosis with signs of chronic cholestasis, microvesicular steatosis and massive hemosiderosis. The child also had heterozygosity for C282Y and H63D mutations of the hemochromatosis gene. His diagnosis was done by several methods like analysis of the mitochondrial and nuclear genomes, determination of enzyme activities and of the hepatic iron content by standard techniques. Thus Pearson's syndrome may cause microvesicular steatosis, hepatic accumulation of iron and liver cirrhosis in neonates.
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Reference: Stephan Krähenbühl, Stephanie Kleinle, Samuel Henz, Kurt Leibundgut, Sabina Liechti, Arthur Zimmermann, & Ulrich Wiesmann (1999). Journal of Hepatology , Volume 31 , Issue 3 , 550 - 555.
6. Therapeutic approach in a case of Pearson's syndrome.
The case study is about a young girl who had Pearson's syndrome, who later developed the symptoms of Kearns-Sayre syndrome. The drug hydrocortisone was used to treat partial adrenal insufficiency due to which many of the symptoms were improved temporarily with the help of replacement therapy. The syndrome in her case had multiple organs involvements because of which she showed a variety of clinical symptoms. The first organ involvement was bone marrow and then the brain retina, inner ear, and kidney. The distinctive characteristic in her case was partial adrenal insufficiency, which is normally very rarely seen in mitochondrial disorders. The patient was given ubiquinone, carnitine, and hydrocortisone which resulted in improvement of adrenal insufficiency, however, only temporary reversion of the weakness of muscle, ophthalmoplegia and of the fatigue, were testified. Moreover, after a short period of recovery, she developed the de Toni-Debré-Fanconi syndrome and the neurological symptoms recurred.
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Reference: Zaffanello M, & Zamboni G. (2005). Minerva Pediatr. 2005 Jun;57(3):143-6.