Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
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A case of neonatal hemochromatosis in a 3-hour-old male is described. He presented with hypotonia, mild jaundice, and respiratory difficulty immediately after birth. He had no evidence of congenital infection, immune-related hemolysis or exogenous iron uptake. Postmortem examination revealed abnormal facial features. The organs were of normal weight for his age except a small liver and lungs, and a large spleen. The most prominent changes were in the liver and pancreas. The liver was coarsely nodular and fibrotic. The lobular architecture was totally distorted by innumerable multinucleated giant cells, loss or collapse of the hepatocytes, and diffuse fibrosis. A large amount of hemosiderin was seen in the liver, pancreatic acini and thyroid follicular cells. Scanty amount of hemosiderin was also found in the myocardial fibers and renal tubular cells. The pancreas showed hyperplasia and hypertrophy of the islets. The spleen showed severe congestion and a moderate extramedullary hemopoiesis but no deposits of hemosiderin. This patient had three siblings died in neonatal period, one of which had clinical features of neonatal hemochromatosis.
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PMID:Neonatal hemochromatosis--report of an autopsy case. 177 32

Deoxyguanosine kinase deficiency (dGK) is a frequent cause of the hepatocerebral form of mitochondrial depletion syndrome (MDS). A group of 28 infants with severe progressive liver failure of unknown cause was recruited for post mortem search for deoxyguanosine kinase (DGUOK) gene mutations. Four affected patients (14% of the studied group), two homozygotes, one compound heterozygote, and one heterozygote, with DGUOK mutation found on only one allele, were identified. Three known pathogenic mutations in the DGUOK gene were detected, c.3G>A (p.Met1Ile), c.494A>T (p.Glu165Val), and c.766_767insGATT (p.Phe256X), and one novel molecular variant of unknown pathogenicity, c.813_814insTTT (p.Asn271_Thr272insPhe). Profound mitochondrial DNA depletion was confirmed in available specimens of the liver (4%, 15%, and 10% of the normal value) and in the muscle (4%, 23%, 45%, and 6%, respectively). The patients were born with low weights for gestational age and they presented adaptation trouble during the first days of life. Subsequently, liver failure developed, leading to death at the ages of 18, 6, 5.5, and 2.25 months, respectively. Mild neurological involvement was observed in all children (hypotonia, psychomotor retardation, and ptosis). Hypoglycemia (hypoketotic) and lactic acidosis were the constant laboratory findings. Elevated transferrin saturation, high ferritin, and alpha-fetoprotein levels resembled, in two cases, a neonatal hemochromatosis. Liver histopathology showed severe hepatic damage ranging from micronodular formation and cirrhosis to the total loss of liver architecture with diffuse fibrosis and neocholangiolar proliferation. Pancreatic islet cell hyperplasia with numerous confluent giant islets was found in both autopsied infants. Analysis of the natural history of the disease in our patients and the literature data led us to the following observations: (i) islet cell hyperplasia (and hyperinsulinism) may contribute to MDS-associated hypoglycemia; (ii) iron overload may additionally damage mtDNA-depleted tissues; (iii) low birth weight, adaptation trouble, and abnormal amino acids in newborn screening are frequent in dGK-deficient neonates.
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PMID:Post mortem identification of deoxyguanosine kinase (DGUOK) gene mutations combined with impaired glucose homeostasis and iron overload features in four infants with severe progressive liver failure. 2110 80