Recurrence of neonatal haemochromatosis in half sibs born of unaffected mothers.

Abstract

We report two families in which neonatal haemochromatosis was observed in half sibs. In the first family, two successive girls were born of different fathers. In the second family, an affected brother and sister were followed by an affected half brother born after donor insemination. These observations, as well as a previous abstract describing two affected half sisters, revive the debate over the inheritance of neonatal haemochromatosis. Incomplete penetrance or gonadal mosaicism for a dominant disorder, a maternal "environmental factor", or mitochondrial defect may be more suitable explanations than autosomal recessive inheritance in this condition. Alternative modes of fertilisation, such as donor insemination or in vitro fertilisation with donor eggs, should be considered with caution. (JtMed Genet 1996;33:444-449) Key words: neonatal haemochromatosis; half sibs; maternal inheritance.Neonatal haemochromatosis (NH) is a polyvisceral iron storage disorder of prenatal onset. It is characterised by a rapidly progressive hepatic insufficiency with prenatal or perinatal onset and a specific distribution of iron overload similar to that seen in adult chromosome 6 326,mol/l under treatment. However, serum iron increased to 228 itmol/l and liver insufficiency persisted. She had disseminated intravascular coagulation with fibrin degradation products at 160 gg/ml (normal <20).In addition to standard treatment for liver failure, she was given continuous infusion factors II, V, VII, IX, and fibrinogen at a dosage of 50 IU/kg/day without improvement. Death resulted from massive intracranial haemorrhage and multivisceral failure on day 5.Postmortem liver biopsy showed micronodular cirrhosis, mild ductular proliferation and portal inflammation, extramedullary haematopoiesis, and multinucleated hepatocytes. Iron overload was obvious and was concentrated in hepatocytes, without iron accumulation in Kupffer cells. Iron overload was found at necropsy in the pancreas, stomach, adrenal glands, kidneys, thyroid, heart, and salivary glands. AETIOLOGICAL INVESTIGATIONSAs recommended elsewhere,8 appropriate blood and urine tests were performed before death in both children. Combined with postmortem pathological examination, tyrosinaemia, galactosaemia, hereditary fructose intolerance, organic acidaemias, Niemann-Pick type C, glycogenosis I, III, and IV, ocl antitrypsin deficiency, peroxisomal disorders, primary defects of bile acid synthesis, cystic fibrosis, Byler disease, Wolman disease, and neonatal infections were excluded. The mother was aged 22 at the birth of patient 1. Her liver function and basal iron metabolism, assessed six months after the birth of patient 2, showed slightly raised iron (2-04 mg/l, normal range 0 6-1 5) and transferrin (4-12 g/l, normal range from 2-4-3-8 1). On CT scan, attenuation of the liver was normal and the difference from splenic attenuation was not significant. Hepatic, renal, splenic, and adrenal iron storage, estimated through abdominal MRI scan, by TI, T2, and gradient echo sequenc...

Neonatal Hemochromatosis

“…5 NH would affect maternal half-siblings but not paternal half-siblings. 3,6,7 Female survivors of NH went on to have healthy unaffected infants. Thus, NH appeared to be congenital and familial, but not hereditary.…”

Liver transplantation in mitochondrial respiratory chain disorders

“…MRCD may therefore have an autosomal recessive, dominant or X-linked pattern of transmission in the case of a nuclear genomic defect, or present as a maternally transmitted disease in the case of mutations/ deletions in mitochondrial DNA. In such case, the disease could recur in half sibs as observed in neonatal haemochromatosis, another cause of acute liver failure in infancy [10]. In addition to mutations or deletions, depletion of mitochondrial DNA has also been reported.…”

Disparate Clinical Presentation of Neonatal Hemochromatosis in Twins

“…9 There are several instances of maternal half-siblings being affected but not of paternal half-siblings. 8,11,12 Counseling related to future childbearing has been based on making a firm diagnosis in the index case and the assumption of a high recurrence rate. 13,14 At present, there is no test to determine if a pregnancy will be affected, and there is no effective approach to prenatal diagnosis.…”