We report on two sibs with syndromal congenital iron storage disease. Prenatal symptoms were IUGR, hydramnios, and placental hyperplasia. Clinical anomalies included hypertelorism and sparse, thin, curly hair (trichomalacia). Clinical course was marked by intractable diarrhoea, with normal histological and enzymological studies, cholestatic jaundice, hepatomegaly appearing after 30 days, and progressive liver failure, leading to death after a few months. The only metabolic anomaly was progressive hypermethioninemia. Pathologic examination of both children showed a similar pattern of multivisceral iron deposit compatible with a diagnosis of neonatal hemochromatosis: extensive liver fibrosis or cirrhosis with nodular regeneration, cholestasis, ductular proliferation, and hepatic, pituitary, thyroidal, adrenal, and pancreatic iron deposition. The unusual course for neonatal hemochromatosis in both sibs combined with concordant extrahepatic anomalies suggest that they could have a specific iron storage syndrome with possible autosomal recessive inheritance, probably similar to the sibship reported by Stanckler et al. [Arch Dis Child, 57:212-216, 1982].

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...