PANCREAS ALERTS
Am J Gastroenterol 2001; 96:2657-61.
Mutations of the cystic fibrosis gene in patients with chronic pancreatitis.
Truninger K, Malik N, Ammann RW, Muellhaupt B, Seifert B, Muller HJ, Blum HE.
Department of Medicine II, University of Freiburg. Freiburg, Germany.
Several studies have reported an increased frequency of cystic fibrosis gene mutations in idiopathic but not in alcoholic chronic pancreatitis. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis has not yet been analyzed.
The aim of this study was to determine the frequency of cystic fibrosis gene mutations in patients with chronic pancreatitis using a long-term follow-up and to investigate whether patients with mutations have a natural course which is clinically different as compared to those without mutations.
The authors studied 82 patients with chronic pancreatitis and 11 patients with recurrent acute pancreatitis of a well-defined pancreatitis cohort. These patients were screened for the 31 most common cystic fibrosis gene mutations and the impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis was assessed.
A cystic fibrosis gene mutation was detected in five of 49 patients with alcoholic chronic pancreatitis (10.2%; 2.3 times the expected frequency) and in three of 14 patients with idiopathic-juvenile chronic pancreatitis (21.4%; 4.8 times the expected frequency). No mutations were found in the remaining patients with chronic pancreatitis of rare causes, hereditary pancreatitis, and recurrent acute pancreatitis.
In conclusion, these data indicate a significantly increased frequency of cystic fibrosis gene mutations in patients with both alcoholic and idiopathic-juvenile chronic pancreatitis; the natural course was similar in patients with mutations as compared to those without mutations.
The frequency of pancreatic calcifications was significantly higher in patients with alcoholic chronic pancreatitis without mutations. This result was not confirmed in patients with idiopathic-juvenile chronic pancreatitis.
The duration of pain and the frequency of exocrine and endocrine insufficiency was comparable in both subgroups irrespective of the mutation status.
Ann Int Med 2001; 134:777-9.
Maternally inherited diabetes and deafness: a multicenter study.
Guillauseau PJ, Massin P, Dubois-LaForgue D, Timsit J, Virally M, Gin H, et al.
Department of Medicine B, Lariboisiere Hospital, University Paris 7-Denis Diderot. Paris, France.
Maternally inherited diabetes and deafness (MIDD) is related to a point mutation at position 3243 of mitocondrial (mt) DNA. It is present in 0.5-3% of all patients with Type 2 diabetes mellitus. Because there have been few studies done, the clinical description of MIDD and its course still remains incomplete.
The aims of this multicenter study, involving 16 French departments of Internal Medicine, were to assess the clinical presentation of MIDD in a large series of patients and evaluate the prevalence of micro/macro-vascular complications.
A total of 54 patients with overt diabetes (21 men and 33 women) and mt-DNA 3243 mutation were recruited. On average, patients with MIDD were young at the time of onset of diabetes and presented with a normal or low body mass index; none were obese.
Therefore, MIDD encompasses a wide clinical spectrum but a specific clinical profile can be delineated (young age at onset, normal or low body mass index, presence of macular dystrophy, high frequency of renal, cardiac, neuromuscular and psychiatric complications) which may help identify diabetic patients for mt-DNA testing.
Bilateral neurosensory hearing loss was present in 53 of the 54 patients (98%).
Diabetes was the first clinical manifestation of the disease in 24 patients and deafness was the first manifestation in 23 patients; in 7 patients, both conditions were diagnosed simultaneously.
Seventy-three percent of probands had a maternal family history of diabetes. At onset, diabetes was non-insulin-dependent in 87% of patients; however, 46% of them progressed to insulin therapy after a mean duration of approximately ten years.
Macular pattern dystrophy (a specific retinal lesion) was observed in 85% of patients. Forty-three percent of patients had myopathy, 15% had cardiomyopathy, and 18% had neuropsychiatric symptoms. Twenty-eight percent of patients presented diabetic nephropathy.
The exact genetic diagnosis has practical consequences due to its strictly matrilineal transmission: affected males can be reassured that their offspring will not inherit the disease.