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7. Doss MO, Gross U, Puy H, et al. Coexistence of hereditary
coproporphyria and porphyria cutanea tarda: a new form of
porphyria. Med Klin (Munich) 2002; 97: 1-5.
8. Petersen NE, Kaehne M, Christiansen L, Brock A, Hother-
Whipple’s disease
in a father-son pair
Maurizio Ponz de Leon
1
, Athos Borghi
1
,
Francesca Ferrara
1
, Miranda Contri
2
,
Luca Roncucci
1
1
Department of Medicine and Medical Specialties,
2
Department of
Biomedical Sciences, University of Modena and Reggio Emilia,
Modena, Italy
In 1907, George Whipple reported the occurrence of
severe malabsorption (with consequent weight loss),
polyarthritis, cough, diarrhoea and mesenteric lymph
node involvement in a 36-year-old medical missionary
1
.
This was the first description of a new syndrome, and we
now refer to it as Whipple’s disease: a systemic condition
featured by arthralgias, diarrhoea, malabsorption, and
less frequently, central nervous system and cardiac
manifestations
2
. Whipple’s disease is a rare illness, which
has been described predominantly in white, middle-aged
individuals, and appear to be 8 times more frequent in
men than in women
2
. The infective nature of Whipple’s
disease was proposed in 1952
3
, when a patient responded
to antibiotic treatment, and was further confirmed by
electron microscopy, in 1961
4
. More recently, the
Whipple’s bacillus was identified by polymerase chain
reaction (PCR)
5
, and named Tropheryma whipplei.
Moreover, new techniques have been developed for
culturing the organism
6
. Despite the recent advances in
our understanding of Whipple’s disease, the clinical
diagnosis remains difficult. In many cases the disease
begins insidiously, with arthropathy, myalgia or
neurological symptoms that may precede by many years
the appearance of malabsorption, diarrhoea and weight
loss, i.e., the “full-blown” clinical picture. Definitive
diagnosis can be established upon the demonstration of
period acid Schiff (PAS)-positive macrophages on
duodenal biopsies taken at endoscopy. The histological
diagnosis should be confirmed by PCR studies or
electron microscopy
2,7
.
The rarity of Whipple’s disease, its prevalence in some
ethnic groups, the sporadic nature of the infection, and
the difficulty in eradicating the responsible organism and
achieving complete healing, clearly suggest that other
factors should be considered in its pathogenesis. A
genetic susceptibility was suggested by the strong
association (26% of the patients, 4 times more than
expected) with HLA-B27
8
. Moreover, Marth et al.
9
show
that many patients have defects in the production of
interleukin-12 and of interferon-γ, abnormalities that
might impair the ability to clear intracellular organisms
such as T. whipplei. Familial data in Whipple’s disease are
scanty; to our knowledge, two pairs of brothers, a
brother-sister and a father-daughter pair have been
reported
10-13
, whereas in most cases the disease neither
aggregates in kindreds nor seems to be associated with
other clinical conditions. In the present letter we report
the occurrence of Whipple’s disease in a father-son pair.
There is little information on the proband’s relatives; the
father (I-1) died during the second World War at age 54
years, the mother died over 90. In the second generation,
two brothers of the proband died of cancer (leukaemia
and liver) over the age of 70 years. CS (III-6) died at age
25 from an undifferentiated malignancy of unknown
origin. The complete genealogical tree, spanning four
generations, is shown in Figure 1.
The proband, CR (II-5 of Figure 1), is at present a 75-year-
old man, 177 cm tall and weighing 84 kg, who retired
many years ago from his job of butcher. In January 1982,
he was hospitalised for weight loss, malabsorption and
fever. There was no evidence of pancreatic disease, and a
xylose test was normal. Because of a mild impairment of
liver function tests, the patient underwent liver biopsy,
which showed septal fibrosis but no evidence of hepatitis
or nodular regeneration. Owing to the development of
pleural effusions and a strongly positive to tuberculin
skin test, the patient was placed on intramuscular strep-
tomycin and other antibiotics against mycobacterium tu-
berculosis. The treatment induced a slight general im-
provement; the weight (58 kg on admission) increased to
64 kg, the fever disappeared, and the patient was dis-
charged. After 6 months, however, he was readmitted to
the hospital because of a general worsening of the clinical
status. An upper endoscopy showed signs of duodenitis,
Nielsen O, Rasmussen K. DGGE analysis of the
coproporphyrinogen oxidase gene: two new mutations in
DNA from Danish patients with hereditary coproporphyria.
Scand J Clin Lab Invest 2000; 60: 617-25.
Received 26 January 2006; revised 19 June 2006; accepted 26 July 2006.
Address for correspondence: Dr. Maurizio Ponz de Leon, Medicina I, Dipartimento di Medicine e Specialità Mediche, Università degli
Studi di Modena e Reggio Emilia, Policlinico, Via del Pozzo 71, 41100 Modena, Italy. E-mail: deleon@unimo.it
© 2006 CEPI Srl