Genetic, Hematological, and Endocrine Involvement in a Patient with Pearson Syndrome: Clinical Management and Discussion

Abstract

Background: Pearson syndrome (PS) is a rare mitochondrial DNA deletion disorder characterized by pancytopenia and exocrine pancreas dysfunction. Currently, there are less than 150 cases ever reported. The mutations are predominately de novo with only a handful of instances of mother to child inheritance documented. Mortality is typically in early childhood or those making it past oftentimes developing chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS). While no curative treatment exists today, our goal is to document the clinical phenotype of a patient with PS to allow for a greater understanding and management for future patients. Diagnosis: We present the case of a child with PS and associated findings of resolved pancytopenia, ringed sideroblasts, failure to thrive, and renal tubular acidosis. Born premature at 32 weeks and anemic at birth, he required PRBC transfusions twice during his one-month NICU admission. At 2 months old, he was vomiting and appeared pale in which he was admitted and had a hemoglobin of 3.5 g/dL. Found then to have pancytopenia, a bone marrow aspiration and biopsy was performed showing ringed sideroblasts, hypocellularity at 60%, 5-8% blasts, moderate dyserythropoiesis, and dysmyelopoiesis. Phenotypically, he was also referred to genetics for facial dysmorphism with a flat nasal bridge, thin philtrum, and small ears. Upon further genetic testing, he had an 80% Heteroplasmic 5kb deletion including m.8483_13459 encompassing the following genes: MT-ATP8, MT-ATP6, MT-CO3, MT-TG, MT-ND3, MT-TR, MT-ND4L, MT-ND4, MT-TH, MT-TS2, MT-TL2, MT-ND, consistent with PS. Since diagnosis, he has been admitted on several occasions for emesis and metabolic acidosis. Management: Patient has been following up with genetics, hematology, endocrinology, cardiology, gastroenterology, neurology, and nephrology. He had been receiving granulocyte colony-stimulating factor (G-CSF) until the age of 1 and more than 20 transfusions up until 1.5 years old with the pancytopenia having since resolved. Most recent values show a hemoglobin of 13.9 g/dL, WBC 5,600/mcL, and platelets still low at 86,000/mcL. He has been evaluated for short stature with height and weight both below the 1st percentile and IGF-1 low at 25 leading to considerations for a G-tube and/or GH supplementation. He continues to receive physical therapy for low muscle mass. He is currently taking sodium bicarbonate, magnesium bicarbonate, and levocarnitine due to deficiencies, pancrelipase for exocrine pancreatic insufficiency, and leucovorin for anemia. He is also seeing dermatology for a hemangioma, facial telangiectasias on the forehead and cheeks, as well as skin photosensitivity and hypopigmentation of the arms and legs. Discussion/Conclusion: With PS being discovered less than 50 years ago, more research still needs to be done to better understand clinical phenotype and treatment management. Resolved pancytopenia, ringed sideroblasts, failure to thrive, and renal tubular acidosis have all been seen in the literature and in our patient. Other areas however are still being assessed. While failure to thrive has been reported, the efficacy of growth hormone supplementation has not been adequately described. With regards to skin findings, hypopigmentation has been reported in the literature in reference to various mitochondrial diseases, however there are limited findings in specific with reference to PS. Furthermore, it would be beneficial to see whether others with PS have any of the same facial dysmorphisms to aid in future diagnosis. Gene therapies and other therapeutics are newly emerging for mitochondrial diseases and it is our hope that PS will have more advanced treatment options in the future.