Mitochondrial Cytopathy Disease presenting in infancy
as sideroblastic anemia, pancytopenia, defective oxidative phosphorylation,
exocrine pancreatic insufficiency, and variable hepatic, renal, and
endocrine failure. Death often occurs in infancy as a consequence of
infection or metabolic crisis. Those who survive the first year of life
present with Kearns-Sayre Syndrome (progressive mitochondrial disorder
characterized by progressive external ophthalmoplegia and weakness of
Pearson Marrow-Pancreas Syndrome.
Originally described by Pearson et al. in 1979, the
disorder involves the hematopoietic system (sideroblastic anemia with
vacuolization of marrow precursors) and exocrine pancreatic dysfunction, as
well as liver and kidney dysfunction.
Unknown; isolated case reports only.
The existence of an autosomal dominant
mitochondrial DNA breakage syndrome is well established. There is
mitochondrial DNA (mtDNA) deletion in a lymphoblastoid cell line in patients
with Pearson Syndrome. Both sexes are affected.
This disease results from a defect of oxidative
phosphorylation associated with deletions of the mitochondrial DNA. Severe,
transfusion-dependent, macrocytic anemia starting in infancy may be
associated with variable degree of neutropenia and thrombopenia. In addition
there may be defects in liver (hepatic failure), kidney (proximal
tubulopathy), gut (watery diarrhea), and skin (patchy erythematous lesions).
High lactate/pyruvate molar ratios in plasma.
Pearson Syndrome resembles the Shwachman Syndrome in
some ways in that bone marrow dysplasia and exocrine pancreas failure also
occurs. However, the disorders differ in bone marrow morphology and
Shwachman Syndrome also includes metaphysical chondrodysplasia. The bone
marrow in patients with Pearson Syndrome is characterized by marked
vacuolization of myeloid precursors and ringed sideroblasts and reduction in
the size and number of the islets, fibrosis, and acinar atrophy of the
pancreas. In addition, there is vacuolation of renal tubules,
glomerulosclerosis, and “ragged red” fibers of skeletal muscles. mtDNA
deletion is present in liver and skeletal muscle biopsies. In 1992, Gibson
et al. detected 3-methylglutaconicaciduria in four patients with Pearson
Syndrome and suggested that this finding may be a useful marker for Pearson
Syndrome and more specific than other organic acids identified in this
disorder. This disorder is fatal and few patients survive beyond a few
Typical hematologic symptoms
(transfusion-dependent severe macrocytic anemia, neutropenia,
thrombocytopenia) in early infancy. Insulin-dependent diabetes mellitus may
develop during the course of the illness. There is failure to thrive
secondary to exocrine pancreatic dysfunction and malabsorption. A few
neonates with Pearson Syndrome have been reported to present with lactic
acidosis. The tissue distribution and relative proportions of abnormal mtDNA
molecules determine the phenotype and the clinical course. In general, the
clinical course is progressive and death occurs in infancy. Some surviving
patients later developed features of Kearns-Sayre Syndrome (another mtDNA
deletion disorder with retinopathy, myopathy, and cardiac involvement),
depending on the distribution of deleted mtDNA.
The diagnosis of mitochondrial
disease should be considered in any child with a multisystem neurological
disorder or who is being investigated for hypotonia. Anesthesia-related
morbidity and mortality risk is ...