Very long chain acyl-CoA dehydrogenase deficiency in a pair of mildly affected monozygotic twin sister in their late fifties.

Very long-chain acyl-CoA dehydrogenase (VLCAD) catalyses the initial step of mitochondrial beta-oxidation of long-chain fatty acids with a chain length of 14 to 20 carbons. Deficiency of VLCAD activity has been associated with a range of phenotypes, including a severe lethal form presenting in the infantile period and a milder variant with onset in childhood. Varying rates of residual enzyme activity partly explain the heterogeneity in presentations. Here we report the course of disease in a pair of monozygotic twin sisters who were diagnosed in their late forties during an evaluation for rhabdomyolysis and fatigue. Interestingly, the patients' complaints were most severe during puberty and declined significantly after the menopause. The basis for this observation is uncertain, but may be related to hormonally-mediated changes in lipid metabolism that may occur at these times. As metabolic decompensation can be associated with significant morbidity, timely diagnosis of VLCAD deficiency is important. The introduction of appropriate dietary measures (i.e. avoidance of fasting, long-chain fat restriction and supplementation with medium-chain triglycerides) greatly reduces the likelihood of complications.

Sympathetic skin response following thermal, electrical, acoustic, and inspiratory gasp stimulation in familial dysautonomia patients and healthy persons.

To determine whether sympathetic skin response (SSR) testing evaluates afferent small or efferent sympathetic nerve fiber dysfunction, we studied SSR in patients with familial dysautonomia (FD) in whom both afferent small and efferent sympathetic fibers are largely reduced. We analyzed whether the response pattern to a combination of stimuli specific for large or small fiber activation allows differentiation between afferent and efferent small fiber dysfunction. In 52 volunteers and 13 FD patients, SSR was studied at palms and soles after warm, cold and heat as well as electrical, acoustic, and inspiratory gasp stimulation. In addition, thermal thresholds were assessed at four body sites using a Thermotest device (Somedic; Stockholm, Sweden). In volunteers, any stimulus induced reproducible SSRs. Only cold failed to evoke SSR in two volunteers. In all FD patients, electrical SSR was present, but amplitudes were reduced. Five patients had no acoustic SSR, four had no inspiratory SSR. Thermal SSR was absent in 10 patients with abnormal thermal perception and present in one patient with preserved thermal sensation. In two patients, thermal SSR was present only when skin areas with preserved temperature perception were stimulated. In patients with FD, preserved electrical SSR demonstrated the overall integrity of the SSR reflex but amplitude reduction suggested impaired sudomotor activation. SSR responses were dependent on the perception of the stimulus. In the presence of preserved electrical SSR, absent thermal SSR reflects afferent small fiber dysfunction. A combination of SSR stimulus types allows differentiation between afferent small or efferent sympathetic nerve fiber dysfunction.

Dietary management reverses grooving and abnormal polarization of hair shafts in argininosuccinase deficiency.

We have observed that the fragile hair of two untreated patients with argininosuccinic aciduria showed abnormal alternating zones of bright and dark banding by polarizing microscopy. Scanning electron microscopy documented discontinuous grooves with a 50 to 100 microns periodicity. Results of amino acid analysis of the hair were essentially normal. After the patients were treated with a low-protein, arginine-supplemented diet, the hair assumed a normal appearance. Five patients already treated with diet showed no hair abnormalities. The pathogenesis of the hair changes in unknown, but our findings suggest that products generated in the disease can adversely affect metabolically active tissue such as hair.