The Spectrum of Hepatic Involvement in Patients With Telomere Disease.

Loss-of-function mutations in genes that encode for components of the telomere repair complex cause accelerated telomere shortening. Hepatic involvement has been recognized as a cause of morbidity in telomere diseases, but very few studies have characterized the nature and extent of liver involvement in affected patients. We report the prevalence and characteristics of liver involvement in a large cohort of patients with telomere disease evaluated serially at the National Institutes of Health. One hundred twenty-one patients with known or suspected telomere disease were screened; 40 patients with liver involvement were included in the current study. Median follow-up was 2.4 years. Data were collected regarding their demographic information, laboratory analysis, imaging, and histopathology. Forty patients (40% of the cohort) with a median age of 42 years were found to have liver involvement. Liver enzyme elevation was cholestatic in pattern; 8 (21%) had drug-related enzyme elevations. The most common imaging finding was increased hepatic echogenicity on ultrasound in 39% (9) of patients, followed by hepatomegaly in 26% (6). Biopsies were infrequent because of risk associated with thrombocytopenia, but in 6 patients, there were varying findings: nodular regenerative hyperplasia, steatohepatitis, hemosiderosis, cholestasis, and cirrhosis with hepatic steatosis. Almost half the cohort had pulmonary diffusion abnormalities, and 25% died during the follow-up period. Conclusion: In patients with telomere disease, hepatic involvement is common and can present in diverse ways, including elevated liver enzymes as well as histopathologic and imaging abnormalities. Liver disease has important implications for morbidity and mortality in patients with telomere disease.

A Case of Congenital Dyserythropoeitic Anemia Type IV Caused by E325K Mutation in Erythroid Transcription Factor KLF1.

Congenital dyserythropoetic anemias (CDA) represent a heterogeneous group of inherited red cell disorders resulting in ineffective erythropoiesis. Several CDA variants have been identified. KLF1 is a transcription factor required for cell division in erythroid differentiation and maturation, and the switch from fetal to adult hemoglobin. Mutations in KLF1 gene can result in a wide range of phenotypes. This case illustrates the E325K mutation in KLF1 presenting with severe anemia in infancy, persistently elevated fetal hemoglobin, and progressive improvement with age. This case of CDA because of KLF1 mutation highlights the common features and expected disease course of CDA type IV.

Knuckle cracking and hand osteoarthritis.

BACKGROUND: Previous studies have not shown a correlation between knuckle cracking (KC) and hand osteoarthritis (OA). However, one study showed an inverse correlation between KC and metacarpophalangeal joint OA. METHODS: We conducted a retrospective case-control study among persons aged 50 to 89 years who received a radiograph of the right hand during the last 5 years. Patients had radiographically proven hand OA, and controls did not. Participants indicated frequency, duration, and details of their KC behavior and known risk factors for hand OA. RESULTS: The prevalence of KC among 215 respondents (135 patients, 80 controls) was 20%. When examined in aggregate, the prevalence of OA in any joint was similar among those who crack knuckles (18.1%) and those who do not (21.5%; P = .548). When examined by joint type, KC was not a risk for OA in that joint. Total past duration (in years) and volume (daily frequency × years) of KC of each joint type also was not significantly correlated with OA at the respective joint. CONCLUSIONS: A history of habitual KC-including the total duration and total cumulative exposure-does not seem to be a risk factor for hand OA.