Transthyretin Val71Ala mutation in a Dutch family with familial amyloidotic polyneuropathy.

A Dutch family with familial amyloidotic polyneuropathy associated with the transthyretin mutation Val71Ala is described. This is the third reported family with this mutation, causing at the protein level an unstable TTR monomer and at the clinical level progressive wasting, polyneuropathy, autonomic dysfunction and vitreous opacities.

Determination of ammonia in cerebrospinal fluid using the indophenol direct method.

We have determined ammonia in cerebrospinal fluid (CSF) with the indophenol direct method. The results were compared with an enzymatic method. The method is very simple, and precision (coefficient of variation 1.6%) and linearity (r = 0.9999, p < 0.001) of the method are excellent. The recoveries of the method are very good (within-sample recovery: range 88-93, median 93%; between-sample recovery: 88-93, median 91%). In a population of 23 neurological patients not suffering from liver disease, the reference values ranged from 8 to 26, median 18 microM. Males and females did not differ (p = 0.5). The values obtained with the indophenol method were equal to the enzymatic method (range 9-28, median 18 microM, p = 0.6). On storage in the deep freeze (-20 degrees C), there was no change in CSF ammonia concentration for at least 1 mo. When stored at 4 degrees C (refrigerator), ammonia determinations have to be performed within 2 d. CSF storage at room temperature results in artificially elevated ammonia levels and should be avoided.

Miyoshi-type distal muscular dystrophy. Clinical spectrum in 24 Dutch patients.

Miyoshi-type distal muscular dystrophy has now been found to be more frequent outside Japan than was previously thought. We studied 24 Dutch patients with Miyoshi-type distal muscular dystrophy and focused on its clinical expression and natural history, muscle CT-scans and muscle biopsy findings. Our study shows that Miyoshi myopathy is a heterogeneous, slowly progressive disorder. The disease starts with weakness and atrophy of the calves and progressively involves the proximal leg and hip muscles and, in a later stage the shoulder and upper arm muscles. After 10 years disease duration, one-third of the patients are dependent on wheelchairs for out-of-door transportation. Disease progression is related to disease duration and not to early age of onset of symptoms. Onset may be at any age and is asymmetrical in roughly half of the cases. Four cases had been initially diagnosed as idiopathic hyper-CK-aemia.

Capillary gas chromatographic determination of cholestanol/cholesterol ratio in biological fluids. Its potential usefulness for the follow-up of some liver diseases and its lack of specificity in diagnosing CTX (cerebrotendinous xanthomatosis).

The concentration ratios of cholestanol/cholesterol in biological materials (serum, cerebrospinal fluid and tendon biopsy) were determined using a capillary gas chromatographic method. The method was validated by gas chromatography-mass spectrometry. The ratio was determined in several groups of patients: (a) patients with cerebrotendinous xanthomatosis (in serum, cerebrospinal fluid and tendon biopsy), before and during chenodeoxycholic acid therapy, (b) patients receiving cholestyramine therapy (in serum), (c) patients suffering from various liver diseases (in serum) and (d) one patient before and after liver transplantation (in serum). It can be concluded that the cholestanol/cholesterol concentration ratio is a potentially useful parameter for monitoring liver diseases but is not specific for establishing the diagnosis of cerebrotendinous xanthomatosis.

Diagnosis of cerebrotendinous xanthomatosis (CTX) and effect of chenodeoxycholic acid therapy by analysis of urine using capillary gas chromatography.

By means of capillary gas chromatography urine samples of patients with cerebrotendinous xanthomatosis (CTX) were investigated before and during treatment by oral administration of chenodeoxycholic acid. The occurrence of various conjugated bile alcohols, presumably glucuronides, was demonstrated, the major compound being 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23 xi, 25-pentol. In the bile acid fraction norcholic acid and hydroxycholic acid were shown to be present in considerable amounts. In this way the presence of CTX can be demonstrated conclusively. After chenodeoxycholic acid therapy the excretion of both abnormal bile acids as well as of bile alcohols rapidly decreased within a few weeks, showing the effectiveness of the treatment. By early discovery and subsequent therapy it may be possible to prevent the onset of the detrimental symptoms such as mental deficiency, caused by the accumulation of cholestanol and cholesterol in CTX patients.

Polyneuropathy and benign monoclonal gammopathy.

Recently the rather frequent occurrence of benign monoclonal gammopathy (BMG) has been reported in peripheral neuropathy. Sometimes this syndrome is part of a multisystemic disorder in which organomegaly, endocrine disturbances, skin changes and focal bone lesions may also occur. The clinical picture and the cerebro-spinal fluid findings resemble the chronic relapsing Guillain-Barré syndrome. The polyneuropathy seems to be of the primarily demyelinating type. The pathogenetic relationship with the gammopathy is as yet not clear, but treatment of the plasma cell dyscrasia has a favourable effect on the polyneuropathy. We report our experiences with 5 patients with polyneuropathy and BMG and compare our clinical, laboratory and histological data with the literature.

Polyneuropathy after massive exposure to parathion.

Many organophosphorus compounds, including the organophosphate insecticides, may cause polyneuropathy of delayed onset. An exception is parathion, which has been considered the prototype of nonneurotoxic cholinesterase inhibitors. Nevertheless, we describe a patient with delayed polyneuropathy after suicidal ingestion of parathion.