Clinical manifestations and enzymatic activities of mitochondrial respiratory chain complexes in Pearson marrow-pancreas syndrome with 3-methylglutaconic aciduria: a case report and literature review

Abstract

• No clinical characteristics distinguish between Pearson marrow-pancreas syndrome patients with and without 3-methylglutaconic aciduria.

Pearson marrow‐pancreas syndrome with cardiac conduction abnormality necessitating prophylactic pacemaker implantation

“…Krauch et al reported a 5-year-old with worsening cardiac function that mainly involved the left ventricle (Krauch et al, 2002). An autopsy study of a 3-year-old girl found that there was markedly reduced mitochondrial enzyme activity in the heart and other organs like the liver and muscles, although there were no clinical cardiac manifestations in that patient (Sato et al, 2015 (Grady et al, 2014;Kabunga et al, 2015). KSS is another mitochondrial disorder with onset before 20 years of age that classically involves the eyes and heart.…”

“…Krauch et al reported a 5‐year‐old with worsening cardiac function that mainly involved the left ventricle (Krauch et al, ). An autopsy study of a 3‐year‐old girl found that there was markedly reduced mitochondrial enzyme activity in the heart and other organs like the liver and muscles, although there were no clinical cardiac manifestations in that patient (Sato et al, ). Cardiovascular pathologies most commonly determine life expectancy, but little is known about the nature of the underlying cardiac abnormality in patients with PS.…”

“…Cardiac involvement in KSS manifests as conduction abnormalities of varying degrees in more than 50% and sudden cardiac death is reported in as high as 20% of the patients (Chawla, Coku, Forbes, & Kannan, ; Kabunga et al, ). Many of the mitochondrial DNA deletion syndromes (PS, KSS, chronic progressive external ophthalmoplegia (CPEO), and others) have reduced enzymatic activities of common mitochondrial respiratory chain complexes (MRCC) (Sato et al, ). We hypothesize that the same mechanism that involves the cardiac muscles and conduction system in KSS could possibly be the reason for the cardiac involvement in PS as well, but this needs to be further studied and confirmed through molecular diagnostics.…”

“…Pearson marrow‐pancreas syndrome (PS) is an exceedingly rare mitochondrial disorder, involving multiple systems mainly the hematologic system, exocrine and endocrine pancreas, liver, muscle, kidneys, and nervous system (Rötig et al, ; Sato et al, ). Since Pearson's initial report in 1979, there have been only about 100 cases described till now (Manea et al, ).…”

Broad Phenotypic Heterogeneity and Multisystem Involvement in Single mtDNA Deletion-associated Pearson Syndrome

“…With regard to the phenotype of Pearson syndrome, it has to be stressed that it is not confined to the bone marrow and the pancreas as originally reported, but is in fact a multisystem disease ( Table 1 ) ( 5 ). Affected organs other than the bone marrow and the pancreas include the kidneys (Fanconi syndrome (glucosuria, hyperphosphatemia, proteinuria, aminoaciduria), renal insufficiency, global sclerosis of glomerula, 3-methyl glutaconic aciduria ( 6 ), tubulopathy and tubular atrophy) ( 5 ), the liver (steatosis ( 6 ), liver dysfunction ( 6 ), hepatomegaly ( 6 ), or vacuolated hepatocytes) ( 6 , 7 , 8 ), the central nervous system (seizures, ataxia, retarded speech development, muscle hypotonia, hypointensities of the brain stem, or subcortical white matter lesions with white or grey matter lesions ( 9 ), or as movement disorders, particularly tremor) ( 9 ), the eyes (retinal or corneal compromise ( 9 ), corneal endothelial dysfunction) ( 8 ), the endocrine organs (growth retardation with short stature, diabetes, hypoparathyroidism ( 9 ), or adrenal insufficiency) ( 10 ), the heart (myocardial thickening, repolarisation abnormalities, QT-prolongation, bicuspid right ventricle ( 9 ), or as complex–IV deficiency) ( 6 ), the blood (anemia, leucopenia, thrombocytopenia, acute myeloid leukemia) ( 9 ), the skin (focal hyperpigmentation, café aux lait spots ( 9 ), or as cutaneous zygomatosis ( 11 )), the gastro-intenstinal tract (duodenal ulcer, diarrhea ( 12 , 13 ), reflux, or malabsorption ( Table 1 ), the skeletal muscle (ptosis, muscle weakness, or myopathy ( 6 )), or other abnormalities (e.g. splenomegaly ( 9 )).…”