Alfred J. Spiro

Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome.

The cerebro-hepato-renal syndrome is a rare familial malady with cerebral, renal, and skeletal abnormalities, severe hypotonia, cirrhosis, iron and lipid storage, and death within 6 months. Correlated electron microscopic, histochemical, and biochemical studies demonstrate defects in two oxidative organelles. Peroxisomes cannot be found in hepatocytes and renal proximal tubules. In hepatocytes and cortical astrocytes, mitochondria are distorted in their appearance and glycogen stores are increased. Oxygen consumnption of brain and liver mitochondrial preparations with succinate and with substrates reducing nicotinamide adenine dinucleotide is markedly diminished, but the consumption is normal with ascorbate and tetramethylphenylenediamine, which suggests a defect in electron transport prior to the cytochromes. Histochemical studies of mitochondrial oxidation point to a defect between the succinate dehydrogenase flavoprotein and coenzyme Q, possibly in the region of nonheme iron protein.

Disuse atrophy of skeletal muscle. A morphometric study using image analysis.

A morphometric study of disuse atrophy was done on the rat anterior tibilalis muscle over a 13-day period after immobilization of the hind leg by pinning the knee and ankle joints. Cross-sectional areas of individual muscle fibers were measured using image analysis, a new and precise technique. Three types of muscle fibers, light, medium and dark, were defined using a modified myosin-ATPase reaction on cryostat-cut sections. Each of the 3 fiber types was found to show a degree and time course of atrophy unique to itself. At the 0.01 confidence level, the dark fibers (with strongest ATPase reaction) did not shrink significantly. Both the light (ATPase negative) and medium fiber did show significant atrophy at that level; the light shrinking more than the medium. Simple visualization of the light microscopic images was often found to be misleading. Thus, the need was documented for a precise technique for analysis of fiber size distribution.

Hereditary Spastic Paraparesis with Sensory Neuropathy

The authors report the clinical and laboratory assessment of a family in which several members are involved with a neurological disorder characterized by varying degrees of spastic paraparesis associated with sensory deficits. The literature regarding this unusual disorder, which in this family appears to be autosomal dominant, is reviewed and the difficulty in anatomical localization is emphasized.

Neonatal adrenoleukodystrophy presenting as infantile progressive spinal muscular atrophy

Two siblings with neonatal adrenoleukodystrophy are described. The signs and laboratory data documenting infantile progressive spinal muscular atrophy included the initial presentation of 1 sibling with neonatal adrenoleukodystrophy. These patients indicate that neonatal adrenoleukodystrophy should be considered in the differential diagnosis of infantile progressive spinal muscular atrophy.

NEUROLOGICAL COMPLICATIONS IN INFANTS WITH AIDS

The clinical symptomatology of children with AIDS is similar to that observed in adults including fever, weight loss, diffuse lymphadenopathy and opportunistic infections. In adults, unusual neurological complications including progressive encephalopathy were recently reported. Since 1979, we have noted neurological abnormalities in 6 children with AIDS. 5 patients have not attained appropriate milestones, with severe global delay in areas of gross motor control, fine motor control, social functioning and language. Physical examination revealed spastic diplegia, hyperreflexia and positive Babinski in 4 with diminished muscular tone in 5 infants. 1 had seizures. Cerebrospinal fluid was acellular with normal protein and glucose. Skull X-rays have been negative. CT scans, with and without contrast in 4 children, displayed progressive cerebral atrophy. 1 showed intracerebral calcifications. EEGs showed diffuse slow waves with subsequent studies demonstrating further slowing of electrical activity. 4 of the 6 patients have continued neurologic deterioration with further loss of developmental milestones.