1/64. Nonocclusive small bowel infarction in familial dysautonomia syndrome. The authors report a case of a 14-year-old boy with familial dysautonomia (FD) in whom a small-bowel infarction developed during a dysautonomic crisis. Atypical features of the presentation included hypotension with prolonged fever and abdominal distension. The authors postulate that the bowel infarction was caused by prolonged hypoperfusion. It is recognized that the small bowel in normal subjects can adapt to periods of ischemia without irreversible injury. The authors speculate that the known abnormal systemic cardiovascular regulation in patients with FD may adversely affect splanchnic blood flow, which led to the catastrophic consequences in this case. This report draws attention to the risk of significant ischemic complications during a dysautonomic crisis, especially in the face of atypical features, and emphasizes the challenging cardiovascular management of such patients. ( info) |
2/64. Ictal SPECT during autonomic crisis in familial dysautonomia. The authors report results of SPECT cerebral perfusion studies in two patients with familial dysautonomia (FD) during dysautonomic crises and when clinically stable. SPECT imaging studies used 99mTc ethylene cysteine dimer. During dysautonomic crises, regions in the temporoparietal and frontal lobes had increased uptake. Uptake in these areas was less during asymptomatic periods. Episodic asymmetric cerebral perfusion during crises especially affecting the frontal and temporal lobes is suggestive of ictal activity. ( info) |
3/64. Acute autonomic neuropathy. Its occurrence in infectious mononucleosis. A 13-year-old girl with acute onset of symptoms limited to autonomic dysfunction was found to be suffering from infectious mononucleosis. With symptomatic therapy, improvement gradually occurred over a period of seven months. The documentation of this case widens the spectrum of disorders to be considered as a cause of so-called acute pandysautonomia or autonomic neuropathy. ( info) |
4/64. Congenital insensitivity to pain: report of two cases. Congenital indifference or insensitivity to pain (CIP) is a rare syndrome. It mimics a number of other syndromes categorized under peripheral sensory neuropathies, often making early diagnosis difficult. Two cases from the middle east are presented, highlighting possible diagnostic, and management difficulties. ( info) |
5/64. Familial dysautonomia: a diagnostic dilemma. chronic lung disease with signs of an autoimmune disease. We present an 11-year-old girl with sensory and autonomic neurological dysfunction, and respiratory insufficiency caused by recurrent aspiration. The diagnosis of familial dysautonomia (FD) was confirmed by a missing axonal flare to histamine, miosis in response to conjunctival methacholine and homozygous polymorphic linked markers DS58(18) and DS159(7) on chromosome 9. Ashkenazi Jewish descent could not be ascertained by history. A variety of positive tests for autoantibodies were initially interpreted as evidence for systemic lupus erythematosus vs. overlap syndrome with pulmonary, cerebral, skin, and ocular involvement. The diagnosis of FD was delayed because of the rarity of this disorder in germany (second case reported). We discuss possible explanations for the misleading immunological findings, including interference by antibodies binding to milk proteins used as blocking reagents in enzyme-linked immunoassays and circulating immune-complexes due to chronic aspiration pneumonitis. ( info) |
6/64. Pure pan-dysautonomia with recovery. Description and discussion of diagnostic criteria. The patient described in this report appears to have had a unique, severe, pure pan-dysautonomia, and has been investigated in sufficient detail to specify precisely the disorders of functions subserved by the autonomic nervous system. Though we cannot rule out the possibility of an unknown autonomic toxin, we have no evidence for it and suggest that our patient's disorder be considered an acute polyneuritis, restricted to the autonomic system. comment is made on tests of autonomic dysfunction and on the reliance which can be placed upon the results. ( info) |
7/64. Identification of the first non-Jewish mutation in familial Dysautonomia. Familial Dysautonomia is an autosomal recessive disease with a remarkably high carrier frequency in the Ashkenazi Jewish population. It has recently been estimated that as many as 1 in 27 Ashkenazi jews is a carrier of FD. The FD gene has been identified as IKBKAP, and two disease-causing mutations have been identified. The most common mutation, which is present on 99.5% of all FD chromosomes, is an intronic splice site mutation that results in tissue-specific skipping of exon 20. The second mutation, R696P, is a missense mutation that has been identified in 4 unrelated patients heterozygous for the major splice mutation. Interestingly, despite the fact that FD is a recessive disease, normal mRNA and protein are expressed in patient cells. To date, the diagnosis of FD has been limited to individuals of Ashkenazi Jewish descent and identification of the gene has led to widespread diagnostic and carrier testing in this population. In this report, we describe the first non-Jewish IKBKAP mutation, a proline to leucine missense mutation in exon 26, P914L. This mutation is of particular significance because it was identified in a patient who lacks one of the cardinal diagnostic criteria for the disease-pure Ashkenazi Jewish ancestry. In light of this fact, the diagnostic criteria for FD must be expanded. Furthermore, in order to ensure carrier identification in all ethnicities, this mutation must now be considered when screening for FD. ( info) |
8/64. Long-term survival in Stuve-Wiedemann syndrome: a neuro-myo-skeletal disorder with manifestations of dysautonomia. Stuve-Wiedemann syndrome (SWS) is a multiple congenital anomalies syndrome mostly considered to have an early lethality. Only few patients have been reported with long survival; therefore, the clinical phenotype with age has not yet been clearly characterized. We report on two patients with SWS aged 12 and 3 years who have both the osteodysplastic symptoms of the entity as well as autonomic nervous system symptoms resembling familial dysautonomia: lack of corneal reflex and neuropathic keratitis, absence of fungiform papillae, ulcerations of the tongue, paradoxical sweating at low temperature, patellar hyporeflexia, and progressive scoliosis. The clinical and radiological similarities between patients with SWS and patients with Schwartz-Jampel syndrome have led to the suggestion that these two syndromes are a single entity. SWS and Schwartz-Jampel syndrome type II are now indeed considered to be identical, but the radiographic phenotype of SWS long survivors such as the presently reported patients justifies the distinction between SWS and the classical type of Schwartz-Jampel syndrome. An increased number of lipid droplets in muscle fibers and decreased muscle mitochondrial enzyme activities have been found in one patient, confirming a previously reported association between SWS and respiratory chain abnormalities. ( info) |
9/64. Increased globotriaosylceramide in familial dysautonomia. Familial Dysautonomia (FD) is an autosomal recessive disease of unknown etiology, occurring primarily in Ashkenazi jews. patients are neurologically impaired, with deficits primarily in autonomic and sensory functions. The biochemical and genetic defects have remained elusive, precluding carrier detection and prenatal diagnosis. High-performance liquid chromatography data indicated up to a threefold increase in the neutral glycosphingolipid globotriaosylceramide in Dysautonomic fibroblasts and lymphoblasts. Total ganglioside values, measured by colorimetric, fluorometric or specific sodium borohydride incorporation, were decreased. Affected fibroblasts exhibited a range of pleomorphic phenotypes, such that the usual swirl-like confluent growth pattern of normal fibroblasts was distorted to varying degrees, suggesting abnormalities in the FD plasma membrane, possibly affecting cell-cell contacts. The glycosphingolipid increase could not be accounted for on the basis of markedly decreased alpha-galactosidase activity, as in Fabry's disease, where patients also display decreased autonomic function. ( info) |
10/64. heat stroke in familial dysautonomia. A 14-month-old female with familial dysautonomia was referred to the pediatric department with high fever (41.6 degrees C), watery diarrhea, and vomiting. A few hours later, signs of encephalopathy appeared. Laboratory tests revealed elevated levels of lactate dehydrogenase (3500 U/L), aspartate aminotransferase (640 U/L), alanine aminotransferase (320 U/L), and creatine kinase (28,420 U/L). The diagnosis was heat stroke. Impaired autonomic nervous system function may be another risk factor for the development of heat stroke in young children. ( info) |