The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III), which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.

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Hereditary sensory and autonomic neuropathies: types II, III, and IV.

Continuous arteriovenous hemofiltration using small hollow-fiber hemofilters, without pumps, was used as an alternative to conventional methods of acute dialytic therapy. During a 6-month period, 15 patients had 17 treatments. Mean treatment duration was 98.5 +/- 101.1 (SD) hours (range, 4 to 300 hours), for a total of 1673 hours. Mean output per treatment was 9.5 +/- 4.4 mL/min, which was found to be adequate to control uremia despite a considerable protein intake. Six patients had a significant hemorrhage; however, all 6 had active bleeding and existing coagulopathies before beginning treatment. Overall, continuous arteriovenous hemofiltration was found to be a convenient and safe method for providing continuous fluid, electrolyte, and acid-base balance in patients with inadequate renal function. The treatment was particularly useful in patients with vascular instability or severe fluid overload.

Continuous arteriovenous hemofiltration. A report of six months' experience.

AUTONOMIC disorders are usually characterized by widespread abnormalities in both the sympathetic and the parasympathetic systems; this is true whether the autonomic disorder is associated with cen...

Isolated failure of autonomic noradrenergic neurotransmission. Evidence for impaired beta-hydroxylation of dopamine.

FAMILIAL dysautonomia (Riley-Day syndrome) is a rare disorder characterized by emotional lability, insensitivity to pain, absence of tears, postural hypotension, hypoactive corneal and tendon reflexes, absence of fungiform papillae on the tongue, and a history of neurologic abnormality from birth. Although many features of this syndrome suggest a disorder of peripheral nerve function, no consistent abnormalities have been described. 1 Therefore, the purpose of this communication is to report the results of electrophysiologic, ultrastructural, and quantitative histologic studies of peripheral nerve in a patient with the Riley-Day syndrome. Report of a Case The patient, a 21-year-old man of Jewish extraction, was noted to be limp and listless at birth. Feeding problems were present from the first weeks of life. By the age of 3 years, he had been hospitalized 13 times for recurrent chest infections, corneal ulcerations, hyperpyrexia of unknown etiology, hypotensive episodes, vomiting leading to dehydration and, on one

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=NEUR&articleId=570301&pdfFileName=archneur_24_2_003.pdf

Peripheral nerve abnormalities in the Riley-Day syndrome. Findings in a sural nerve biopsy.

Dopamine-β-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, was measured in the plasma of 146 normal subjects, 26 patients with familial dysautonomia and 33 parents ...

Reduced Plasma Dopamine-β-Hydroxylase Activity in Familial Dysautonomia

1. A tabulation of "essential" and helpful criteria for the diagnosis of familial dysautonomia is presented. The importance of accurate diagnosis is stressed. 2. Two cases where the diagnosis of familial dysautonomia was strongly suggested but was not justified are presented by way of contrast to the typical syndrome. 3. Current literature offering new observations of a pharmacological, physiological and anatomical nature is reviewed. Some of these appear to offer important new diagnostic criteria as well as bases for hypotheses for the pathogenesis of the disorder. 4. An attempt to synthesize the various findings is made. It is apparent that the basic functional defect has not yet been identified, though a humoral anomaly, very possibly enzymatic, still seems a reasonable interpretation of the underlying cause of the physiological abnormalities reported.

Familial dysautonomia differentiated from related disorders. Case reports and discussions of current concepts.

Thoughts about kidney homotransplantation in children

Studies of familial dysautonomia by a team made up of a pediatrician, a neurologist, speech therapists, psychiatrists, psychologists and a psychiatric social worker have been presented in summary form. 1. Facts supporting the theory that this is a condition of genetic origin are enumerated. They are compatible with its being transmitted by an autosomal recessive gene. 2. Evidence of disturbance of statural growth, with frequent significant dwarfing, is presented. 3. Postural hypotension as a regular part of the syndrome is demonstrated. 4. Data showing the variable neurological abnormalities are included. 5. The frequency of disturbance of speech, but not of language organization, is reported. 6. Psychological testing suggests a deterioration with advancing years in dealing with concrete tests, but no significant disturbance in abstract thinking. 7. At the psychosocial level, inadequate adjustment to daily life is seen in all patients. This difficulty is reflected in varying degree by emotional disturbance in the parents. A schematic concept of the dynamics is offered. 8. Drug treatment of the acute crisis is discussed and a plan for daily management of such cases is projected. 9. Avenues for further investigation are briefly mentioned.

Further observations on familial dysautonomia.

A statistical evaluation is presented, which reveals a significantly improved survival of children with nephrosis under modern management. The status of the survivors in a small sample seems much better in the current series. The evidence that such improvement is due to the more intensive use of adrenalactive steroid therapy is circumstantial but highly credible. A program for steroid administration, which has seemed satisfactory, is presented. The risks inherent in such hormone treatment appear to be more than counterbalanced by the reduction in early mortality.

Current management of nephrosis statistical evaluation and a proposed approach to therapy.

The effects of short term ACTH treatment (4 to 6 days) in 14 patients with the nephrotic syndrome are presented. Five patients given eight courses showed complete clearing of edema in seven instances, one failing to show any response to a second course. Four patients given six courses showed significant but incomplete clearing of edema each time. Five patients showed no clinically significant response to seven courses.[See Table 5 in Source Pdf] The type of diuresis with regard to salt and water excretion was similar to that seen with spontaneous diuresis. In all but one instance the patients who failed to have a clinically significant response did, nevertheless, show a slight sodium diuresis after with drawal of the drug. There were no consistent changes in the significant chemical findings in the blood, except that in most cases, regardless of clinical results, a drop in the level of total cholesterol was observed after treatment. Several patients who received sodium lactate by mouth following diuresis did not accumulate edema and had a pronounced increase in the urinary sodium. This suggests that at least temporarily their kidneys were capable of dealing with sodium in normal fashion. The period of post-treatment studies on these patients varies from 7 to 15 months. Some of the patients have remained symptom-free, others have relapsed several times but responded to subsequent periods of treatment, still others after early successes have failed to respond to later ACTH administration. Only one of the group has shown clearing of the urine suggesting a permanent remission. Thus the use of this hormone at best offers only a means of controlling edema of the nephrotic syndrome. Whether its repeated use may alter the over-all prognosis can only be determined after a much longer period of observation. It should, however, prove useful in the study of the mechanism of diuresis.

Conrad M. Riley

Papers

Familial dysautonomia differentiated from related disorders. Case reports and discussions of current concepts.

Thoughts about kidney homotransplantation in children

Further observations on familial dysautonomia.

Current management of nephrosis statistical evaluation and a proposed approach to therapy.

NEPHROTIC SYNDROME: Effect of Adrenocorticotrophic Hormone