PL EN


Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
2011 | 52 | 1 |

Tytuł artykułu

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

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
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 pathogeneity, 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 MDSassociated 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.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

52

Numer

1

Opis fizyczny

p.61-66,fig.,ref.

Twórcy

autor
  • Department of Metabolic Diseases, Endocrinology and Diabetology, Children’s Memorial Health Institute (CMHI), Aleja Dzieci Polskich 20, 04-730, Warsaw, Poland
  • Department of Metabolic Diseases, Endocrinology and Diabetology, Children’s Memorial Health Institute (CMHI), Aleja Dzieci Polskich 20, 04-730, Warsaw, Poland
autor
  • Department of Metabolic Diseases, Endocrinology and Diabetology, Children’s Memorial Health Institute (CMHI), Aleja Dzieci Polskich 20, 04-730, Warsaw, Poland
autor
  • Department of Pathology, Children’s Memorial Health Institute (CMHI), Warsaw, Poland
  • Department of Pathology, Children’s Memorial Health Institute (CMHI), Warsaw, Poland
  • Department of Pathology, Children’s Memorial Health Institute (CMHI), Warsaw, Poland
  • Department of Molecular Biology, University of Gdansk, Gdansk, Poland
autor
  • Department of Medical Genetics, Children’s Memorial Health Institute (CMHI), Warsaw, Poland
  • Department of Medical Genetics, Children’s Memorial Health Institute (CMHI), Warsaw, Poland
autor
  • Department of Biochemistry and Experimental Medicine, Children’s Memorial Health Institute (CMHI), Warsaw, Poland
autor
  • Department of Gastroenterology, Hepatology and Immunology, Children’s Memorial Health Institute (CMHI), Warsaw, Poland
  • Department of Metabolic Diseases, Endocrinology and Diabetology, Children’s Memorial Health Institute (CMHI), Aleja Dzieci Polskich 20, 04-730, Warsaw, Poland
autor
  • Department of Molecular Biology, University of Gdansk, Gdansk, Poland

Bibliografia

Uwagi

PL
Rekord w opracowaniu

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

bwmeta1.element.agro-8b43da25-2d9f-4483-b405-14dc4977dfa0
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.