True about Hemochromatosis is?
ANSWER: (A) Iron deposits in the viscera and its destructionREF: Robbins 8th edn Page 1642-43, Wintrobes 12th ed page 860, 862Option (A); Gray or bronze pigmentation is the most common physical examination abnormality in hemochromatosis homozygotes, occurring in approximately 35 to 84%. Other common physical examination findings include arthropathy (13 to 68%), hepatomegaly- hepatic fibrosis and cirrhosis (54 to 93%), splenomegaly (10 to 55%), irregular heartbeat, congestive heart failure, telangiectases, and loss of midline body hair or testicular atrophy.The morphologic changes in hereditary hemochromatosis are characterized principally by:Deposition of hemosiderin in the following organs (in decreasing order of severity): liver, pancreas, myocardium, pituitary gland, adrenal gland, thyroid and parathyroid glands, joints, and skin (detected by the Prussian blue histologic reaction or by atomic absorption analysis of tissue)Liver cirrhosis (micronodular)Pancreatic fibrosisOption (B) & (C); Penetrance in genetics is the proportion of individuals carrying a particular variant of a gene (allele or genotype) that also expresses an associated trait (phenotype). A condition, most commonly inherited in an autosomal dominant manner, is said to show complete penetrance. Only Hemochromatosis Type 4 & 5 are autosomal dominant, both of which are rare. Since Hemochromatosis shows both autosomal recessive and autosomal dominant pattern it is genetically heterogenous not homogenousWintrobe's 12th ed Table 29.1Heritable DisorderChromosomalAssignmentHeritabilityCause of Iron LoadingHemochromatosis type 16p21.3Autosomal recessiveMutations of HFEHemochromatosis Type 2Alq21Autosomal recessiveUnknownHemochromatosis Type 2B19ql3Autosomal recessiveHepcidin antimicrobial peptide gene mutationsHemochromatosis type 37q22Autosomal recessiveInactivation of transferrin receptor 2Hemochromatosis type 42q32Autosomal dominantFerroportin gene mutationsHemochromatosis type 511q 12-q13Autosomal dominantH-ferritin gene mutationOption (D); Frequency of Hemochromatosis in Men and WomenBecause hemochromatosis is transmitted as an autosomal recessive condition, there should be equal numbers of male and female homozygotes. Overt iron-overload organ injury and illness occur more frequently in men than in women who have this disorder. Women are protected somewhat by the menstrual loss of 15 to 25 mg of iron each month, and by the transfer of approximately 750 mg of iron to the fetus during pregnancy. Menstrual blood losses and pregnancy do not explain all of the differences in body iron stores between male and female homozygotes. It is possible that an additional factor(s) prevents most women with hemochromatosis from absorbing and accumulating as much iron as affected men.
Iron deposits in the viscera and its destruction
Is genetically homogenous
Completely penetrant
Females are more commonly affected than male
Blood