Association of Mutations in the Hemochromatosis Gene With Shorter Life Expectancy
Bathum and colleages investigated whether the frequency of carriers for hereditary hemochromatosis changes as a function of age. Genotyping for the C282Y mutation in the HFE gene (the mutation most often associated with hereditary hemochromatosis) was performed in 1784 subjects aged 45 to 100 years, and a trend toward fewer heterozygotes with age was found. The trend was statistically significant for the whole population and for women, but not for men. This age-related reduction suggests that carrier status is associated with shorter life expectancy.
Genetic Analysis as a Valuable Key to Diagnosis and Treatment of Periodic Fever
In this case report, Simon et al demonstrate the importance of adequately examining family history in a patient with unexplained periodic fever episodes. In the 2 cases described, subsequent genetic analysis of the gene for the tumor necrosis factor (TNF) receptor led to a diagnosis of TNF receptor–associated periodic syndrome (TRAPS), an autosomal dominantly inherited disorder characterized by episodes of fever, arthralgia, and skin lesions. Elucidation of the molecular background has facilitated the treatment of TRAPS because blocking of TNF signaling seems to alleviate the symptoms.
mtDNA Disease in the Primary Care Setting
Mitochondrial DNA (mtDNA) mutations are surprisingly common, with a prevalence of up to 10% in patients with diabetes mellitus, hearing loss, or renal failure. A 36-year-old man with a history of psychosis, seizures, sensorineural hearing loss, and a family history of diabetes mellitus and heart disease had undergone evaluation by primary care physicians for 15 years without a unifying diagnosis. Physiologic, biochemical, and genetic testing established the diagnosis of mitochondrial encephalopathy, lactic acidosis, and stroke-like syndrome. Diagnosing mtDNA disorders requires a careful integration of clinical signs and symptoms with pedigree analysis and multidisciplinary testing. Diagnosis is important to provide genetic counseling, avoid unnecessary evaluation, and facilitate therapy for symptomatic relief.
Genotype and Phenotype Analysis of 171 Patients Referred for Molecular Study of the Fibrillin-1 Gene FBN1 Because of Suspected Marfan Syndrome
In this study, the clinical and molecular data were reviewed for 171 consecutive patients referred for FBN1 analysis because of a diagnosis of Marfan syndrome (MFS) or signs suggestive of MFS. A diagnosis of MFS based on the Ghent criteria was highly correlated with an FBN1 mutation (66%). Fifty percent of children with "emerging" MFS had mutations, whereas only 5% of patients with Marfan-related conditions had mutations. These data show first that a comprehensive clinical evaluation is mandatory before establishing a definitive diagnosis and second, that FBN1 mutation analysis may be helpful, particularly in families displaying phenotypic variability or to identify children at risk for MFS who need careful clinical follow-up.
Hereditary Angioedema: A Broad Review for Clinicians
Hereditary angioedema (HAE) is an autosomal dominant disease that afflicts l in 10 000 to 1 in 150 000 persons. It is an uncommon condition that may present with rather common symptoms and may be misdiagnosed in certain circumstances. Hereditary angioedema manifests as recurrent attacks of intense, massive, localized edema without concomitant pruritus. Skin, as well as visceral organs, may be involved by the typically massive local edema. Involvement of the upper airways may result in severe life-threatening symptoms, including the risk of asphyxiation, unless appropriate interventions are taken. Historically, 2 types of HAE have been described; however, a variant, possibly X-linked, inherited angioedema has recently been described and tentatively named "type 3" HAE. Clinicians should keep this group of disorders in their differential diagnosis of unexplained episodic cutaneous angioedema or unexplained abdominal pain.
HMWK indicates high-molecular-weight kininogen; MAC, membrane attack complex.