577
CASE REPORTS
Patient 1 was born prematurely. Hy-
potonia, ecchymoses, and an eczema-
tous rash were noted at birth. He was
unable to tolerate oral feeding because
of apparent gut hypomotility, and jeju-
nal atresia was suggested by findings
on a barium swallow. Laparotomy on
day 7 of life revealed a structurally nor-
mal but atonic gut. Ganglion cells were
present in biopsy specimens at all lev-
els, but there was complete loss of mu-
cosa with a dense submucosal chronic
inflammatory infiltrate.
Abnormal laboratory values included
a platelet count of 34,000/mm
3
, pro-
thrombin time of 17.4 seconds, and
partial thromboplastin time of 112.4 sec-
onds. Coombs-positive hemolytic ane-
mia and jaundice were ascribed to blood
group incompatibility. Hypothyroidism
(thyroxine level, 4.5 μg/dL; thyrotropin
level, 18.8 mU/L) was present.
The patient was treated with L-thy-
roxine, fluids, and antibiotics, but he
failed to thrive. He died at 19 days
from peritonitis after perforation at
one of the biopsy sites. An autopsy re-
vealed diffuse mucosal erosion of the
entire gastrointestinal tract with ab-
sence of normal crypts and villi. An ex-
tensive chronic infiltrate existed in the
submucosal layer. Pancreatic sections
showed acute and chronic inflammato-
ry infiltrates with areas of fibrosis; islet
Neonatal diabetes mellitus is rare.
1
In
many cases, it improves or resolves
with age, and it is almost always isolat-
ed. Occasionally, it has been reported
in association with other clinical
features including noninfectious en-
teropathy, eczema, and other appar-
ently autoimmune phenomena that
are also rare in infancy.
2-14
In these
cases, it is almost always fatal. In his
catalogue, McKusick
15
divides the pre-
sentations into 3 disorders: diarrhea,
polyendocrinopathy, fatal infection
syndrome (Online Mendelian Inheri-
tance in Man 304930); DM, congenital
insulin-dependent, with fatal secretory
diarrhea (OMIM 304790); and im-
Neonatal diabetes mellitus, enteropathy,
thrombocytopenia, and endocrinopathy: Further
evidence for an X-linked lethal syndrome
Ephrat Levy-Lahad, MD, and Robert S. Wildin, MD
mune dysregulation, neonatal insulin-
dependent diabetes, and diarrhea,
X-linked recessive (OMIM 300063).
Bennett et al
3
called the syndrome
X-linked polyendocrinopathy, immune
dysfunction, and diarrhea. Genetic link-
age to markers in the chromosomal
segment Xp11.23-Xq21.1 has been re-
ported in 2 families.
2,3
In each case, the
gene for Wiskott-Aldrich syndrome,
which resides within the mapped inter-
val, lacked mutations, suggesting that
the root of this syndrome will be found
in a different gene. Here, we describe a
new family (Fig 1) in which 3 males, 2
full brothers and 1 maternal half broth-
er, were affected.
From the Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland; and
Medical Genetics, Medicine A, Shaare Zedek Medical Center, Jerusalem, Israel.
Submitted for publication Mar 27, 2000; revisions received July 3, 2000, and Aug 24, 2000;
accepted Sept 7, 2000.
Reprint requests: Robert S. Wildin, MD, Department of Molecular and Medical Genetics,
Oregon Health Sciences University, Mailcode L103A, 3181 SW Sam Jackson Park Rd,
Portland, OR 97201-3098.
Copyright © 2001 by Mosby, Inc.
0022-3476/2001/$35.00 + 0 9/22/111502
doi:10.1067/mpd.2001.111502
DM Diabetes mellitus
OMIM Online Mendelian Inheritance in Man
WAS Wiskott-Aldrich syndrome
We describe an unusual family with a fatal genetic syndrome of neonatal di-
abetes mellitus (DM), enteropathy, endocrinopathy, and severe infections
with variable thrombocytopenia. All affected individuals are male; X-linked
inheritance is likely. The most common clinical features are neonatal DM,
inanition, and enteropathy; a variety of other autoimmune phenomena are
less frequent. Clinical variability within and among families is common, in-
cluding lack of one or more cardinal features. The syndrome is usually fatal,
but survival is sometimes possible with immunosuppressive therapy. Clini-
cal variability and frequent new mutations may contribute to poor recogni-
tion and underreporting of similar cases. (J Pediatr 2001;138:577-80)