glycogen and Abnormalities--Multiple

The cerebrohepatorenal syndrome of Zellweger (CHRS) is remarkable not only for a distinctive combination of congenital anomalies, but also for an unusual variety of profound metabolic disturbances. After a discussion of the clinical diagnosis of CHRS, abnormalities in the metabolism of peroxisomes, mitochondria, iron, pipecolic acid, glycogen, bile acids, and organic acids are discussed and related to the clinical and other biochemical findings in the syndrome. Attention is also drawn to syndromes with biochemical or clinical abnormalities similar to those of CHRS. Although the biochemical findings indicate major abnormalities in oxidative metabolism, the primary defect remains obscure.

Topics: Abnormalities, Multiple; Amino Acids, Dicarboxylic; Bile Acids and Salts; Brain Diseases; Glutarates; Glycogen; Humans; Iron; Kidney Diseases; Liver Diseases; Microbodies; Mitochondria; Pipecolic Acids; Syndrome

We report on three male newborn infants of a highly inbred Lebanese family presenting with a characteristic phenotype: arthrogryposis multiplex, deafness, large inguinal hernia, hiccup-like diaphragmatic contractions, and inability to suck, requiring nasogastric gavage feeding. All three boys died from respiratory failure during the first 3 months of life. Intra vitam or post mortem examinations revealed myopathic changes and elevated glycogen content of muscle tissue. This new syndrome is probably transmitted in an autosomal recessive mode, although X-linked inheritance cannot be excluded.

Topics: 1,4-alpha-Glucan Branching Enzyme; Abnormalities, Multiple; Arthrogryposis; Consanguinity; Deafness; Family Health; Fatal Outcome; Female; Genes, Recessive; Glycogen; Hernia, Inguinal; Humans; Infant; Infant, Newborn; Male; Pedigree; Phosphorylase a; Polymorphism, Single Nucleotide

Topics: Abnormalities, Multiple; Adolescent; Biopsy; Chromosome Deletion; Chromosomes, Human, Pair 22; Craniofacial Abnormalities; Creatine Kinase; Glycogen; Humans; Male; Microscopy, Electron; Muscle, Skeletal; Muscular Atrophy; Neuromuscular Diseases

Two infant boys with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) are reported. Presenting with neonatal intestinal obstruction, they underwent laparotomies that showed megacystis, microcolon, and aperistaltic shortened small bowel without any mechanical obstruction. Patient 1 gradually improved and is developing normally at home, on a normal diet without genitourinary or gastrointestinal complaints (now 11 years old). Patient 2, who underwent vesicoamniotic drainage antenatally, never developed adequate gastrointestinal or genitourinary function in spite of appropriate diversion and pharmacologic support. He showed progressive deterioration and died at the age of 7 months. Detailed histo-immuno- and ultrastructural pathology assessment, although confirming results in the existing literature in some aspects, showed previously unreported neuronal dysplastic changes associated with increased laminin and fibronectin. Although patient 1 showed ultrastructural features of vacuolar degeneration of smooth muscle as reported in the literature, patient 2 showed ultrastructural and histochemical evidence of excessive smooth muscle cell glycogen storage with severely reduced contractile fibres displaced to the extreme periphery of the cells, suggesting a fundamental defect of glycogen-energy utilization. A deficiency of fiber synthesis as the alternative primary defect is discussed. In both cases, a two-step genetic defect may explain the variability in clinical outcome and pathological findings.

Topics: Abnormalities, Multiple; Colon; Energy Metabolism; Fatal Outcome; Female; Fibronectins; Glycogen; Humans; Infant; Infant, Newborn; Intestinal Obstruction; Laminin; Male; Microscopy, Electron; Muscle, Smooth; Peristalsis; Pregnancy; Syndrome; Urinary Bladder

We report on the autopsy study of a premature boy with multiple joint contractures who died soon after birth of severe lung hypoplasia. Muscle histology showed PAS-positive vacuoles, and electronmicroscopy revealed massive subsarcolemmal and intermyofibrillar accumulation of glycogen. Biochemical analysis of fresh-frozen muscle tissue disclosed increased glycogen content and a complete lack of phosphofructokinase (PFK) activity. The brain showed focal cerebral and diffuse cerebellar white matter gliosis, and patchy loss of internal granular and Purkinje cells in the cerebellar cortex. The spinal cord was normal. This report describes the first case of PFK deficiency, presenting as a lethal fetal akinesia sequence.

Topics: Abnormalities, Multiple; Brain; Contracture; Fatal Outcome; Gliosis; Glycogen; Glycogen Storage Disease Type VII; Humans; Infant, Newborn; Infant, Premature; Joints; Male; Muscles; Phosphofructokinase-1

A case of an unusual congenital myopathy is reported. The boy presented at birth with generalized muscular hypotonia and dysmorphic features. Muscle biopsy at the age of 10 years revealed focal areas with decreased ATPase activity and variable oxidative enzyme activity. There was only one type II fiber in the whole section. 22.5% of fibers had central nuclei, sometimes with radial arrangement of the intermyofibrillary network. Focal lesions displayed strong desmin and weak vimentin immunoreactivity. On electron microscopic examination normal sarcomeres were focally disrupted and mitochondria were absent from these areas; the normal structure was replaced by numerous fragments of sarcoplasmic reticulum, filamentous material, scattered glycogen particles, and the Z-line was replaced by irregular longitudinal streaks of electron-dense fibrillar material. We classify this case as a congenital myopathy with focal loss of cross striations.

Topics: Abnormalities, Multiple; Adenosine Triphosphatases; Desmin; Glycerolphosphate Dehydrogenase; Glycogen; Humans; Immunohistochemistry; Male; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle Hypotonia; Muscle, Skeletal; Muscular Diseases; Myofibrils; NADH Tetrazolium Reductase; Vimentin

Topics: Abdominal Muscles; Abnormalities, Multiple; Cytoplasmic Granules; Glycogen; Humans; Inclusion Bodies; Infant, Newborn; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Testis; Urogenital Abnormalities

Topics: Abnormalities, Multiple; Age Determination by Skeleton; Bone and Bones; Consanguinity; Developmental Disabilities; Female; Foot; Glycogen; Growth Disorders; Hand; Humans; Infant; Intellectual Disability; Male; Microscopy, Electron; Muscles; Muscular Atrophy; Myofibrils; Nerve Degeneration; Pedigree; Rubinstein-Taybi Syndrome; Sarcoplasmic Reticulum

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Animals; Birds; Dwarfism; Embryo, Nonmammalian; Female; Fetal Death; Glycogen; Gonads; Infertility; Jaw Abnormalities; Kidney; Leg; Lordosis; Male; Parathion; Pregnancy