Mitochondrial mosaics in the liver of 3 infants with mtDNA defects

<p>Abstract</p> <p>Background</p> <p>In muscle cytochrome oxidase (COX) negative fibers (mitochondrial mosaics) have often been visualized.</p> <p>Methods</p> <p>COX activity staining of liver for light and electron microscopy, muscle stains, blue native gel electrophoresis and activity assays of respiratory chain proteins, their immunolocalisation, mitochondrial and nuclear DNA analysis.</p> <p>Results</p> <p>Three unrelated infants showed a mitochondrial mosaic in the liver after staining for COX activity, i.e. hepatocytes with strongly reactive mitochondria were found adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue, but not of muscle, demonstrated a decreased activity of complex IV; in both muscle and liver subcomplexes of complex V were seen. Immunocytochemistry of complex IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain revealed severe white matter cavitation in the Pearson case, but only slight cortical atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in leucocytes showed a common deletion in 50% of the mtDNA molecules of the Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome, mtDNA was depleted for 60% in muscle. In the 3rd patient muscular and hepatic mtDNA was depleted for more than 70%. Mutations in the nuclear encoded gene of <it>POLG </it>were subsequently found in both the 2nd and 3rd patients.</p> <p>Conclusion</p> <p>Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the pathogenesis; it indicates whether mtDNA should be assayed. Each time a mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy should be recommended. Mosaics are probably more frequent than observed until now. A novel pathogenic mutation in <it>POLG </it>is reported.</p> <p>Tentative explanations for the mitochondrial mosaics are, in one patient, unequal partition of mutated mitochondria during mitoses, and in two others, an interaction between products of several genes required for mtDNA maintenance.</p

Ovarian torsion in a 12 year old girl

Background: A 12-year-old girl was admitted with acute abdominal pain, nausea and vomiting. She had been in excellent health until 2 years previsouly, when she had the first of several episodes of severe lower abdominal pain. Ultrasonography performed at that time did not show any abnormalities. Physical examination revealed a tender abdomen, mainly in the right lower quadrant, without fever. Psoas and obturator sign were slightly positive. Laboratory tests revealed a leukocyte count of 10,000/mm3 with 92% neutrophils and 5% lymphocytes. CRP was within normal limits. The urine was positive for ketones and leucocytes

Pituitary stalk interruption syndrome

A 5-year-old boy presented at the department of Pediatrics because of parental concerns about his delayed growth which had been slowing since the age of 2.5 years. The patient had no significant familial, perinatal or past medical history. At clinical examination, no abnormalities were present. His stature was below the 5th percentile. Laboratory investigations showed normal serum values of TSH, FT4 and prolactin, but an abnormally low IGF-1 concentration. Bone age (Gruelich and Pyle) was 3 years and 6 months, more than one year below his chronological age. MRI of the brain was performed to rule out a hypothalamichypophyseal lesion (Fig. A-D). Midsagittal T1-weighted MR imaging revealed a small sella with a hypoplastic anterior pituitary gland (dotted arrow). The pituitary stalk was extremely hypoplastic and barely perceptible (dashed arrow). An ectopic posterior pituitary gland (solid arrow) was observed as an area of T1 high signal intensity at the median eminence in the floor of the third ventricle between the right and left optic tract (small arrows)

Two female siblings with congenital heart disease, postaxial polydactyly, ectopic neuropituitary gland, hair anomalies and characteristic facial features : a new syndrome?

We present two siblings from unrelated parents presenting with intrauterine growth retardation, a congenital heart defect, postaxial polyclactyly, a brain malformation (ectopic neuropituitary gland associated with a hypoplastic adenopituitary in one of them, and a hypoplastic cerebellum and vermis in the other), abnormal hair with temporal balding, a striking facial dysmorphism and, at least in the child who survived, postnatal growth retardation and severe developmental delay. This probably represents a novel syndrome