Search

Hartnup disease is a rare genetic disorder of amino acid transport associated with variable and intermittent clinical abnormalities. A family is described in which three siblings had an intermittently progressive neurological disease and two of the affected siblings had the Hartnup-pattern aminoaciduria. Neuropathological examination of one case showed severe diffuse atrophy, generalized neuronal loss in the cortex, and Purkinje cell loss in the cerebellum. In vivo and in vitro studies of intestinal amino acid transport in the surviving sibling indicated a partial defect in the transport of several neutral amino acids (tryptophan, alanine, serine, and methionine) with normal transport of other neutral amino acids (threonine, phenylalanine, histidine, tyrosine, and isoleucine). Transport of glycine, proline, hydroxyproline, and the basic amino acids appeared normal.

Electrophysiological studies were performed on aneurally cultured muscle cells from one patient with adult-onset acid maltase deficiency (AAMD) and from controls. The cells from the patient with AAMD had a higher mean resting membrane potential, a lower input resistance, and a higher incidence of action potentials at resting membrane potential than the control cells. Therefore, sarcolemma maturation was not adversely affected. The AAMD cells had membrane thresholds and action potential amplitudes similar to those of the control cells, and rarely produced repetitive action potentials. Therefore, the membrane instability noted in adult muscle fibers from the patient with AAMD was not present in cultured cells. This study does not support the suggestion that the biochemical and morphological abnormalities present in muscle fibers of patients with AAMD are sufficient to cause the electrical abnormalities.