ABSTRACT
Menkes disease (MD) is a lethal disorder characterized by severe neurological symptoms and connective tissue abnormalities; and results from malfunctioning of cuproenzymes, which cannot receive copper due to a defective intracellular copper transporting protein, ATP7A. Early parenteral copper-histidine supplementation may modify disease progression substantially but beneficial effects of long-term treatment have been recorded in only a few patients. Here we report on the eldest surviving MD patient (37 years) receiving early-onset and long-term copper treatment. He has few neurological symptoms without connective tissue disturbances; and a missense ATP7A variant, p.(Pro852Leu), which results in impaired protein trafficking while the copper transport function is spared. These findings suggest that some cuproenzymes maintain their function when sufficient copper is provided to the cells; and underline the importance of early initiated copper treatment, efficiency of which is likely to be dependent on the mutant ATP7A function.
Subject(s)
Copper-Transporting ATPases/metabolism , Copper/therapeutic use , Menkes Kinky Hair Syndrome/drug therapy , Menkes Kinky Hair Syndrome/enzymology , Adolescent , Adult , Child, Preschool , Humans , Infant , Infant, Newborn , Male , Protein TransportSubject(s)
Feeding Behavior , Nutritional Status , Adolescent , Adult , Child , Humans , Nutrition SurveysABSTRACT
We report on the long-term clinical course of 4 boys with Menkes disease, treated from early infancy with parenteral copper-histidine, with follow-up over 10-20 years. Three of the 4 had male relatives with a severe clinical course compatible with classical Menkes disease. As a consequence of early treatment, our patients have normal or near-normal intellectual development, but have developed many of the more severe somatic abnormalities of the related disorder, occipital horn syndrome, including severe orthostatic hypotension in 2. In addition, 1 boy developed a previously unreported anomaly, namely, massive splenomegaly and hypersplenism as a consequence of a splenic artery aneurysm. Previously reported molecular studies in 2 of these patients had shown gene defects which would have predicted a truncated and probably nonfunctional gene product. Despite the favorable effects on the neurological symptoms, parenteral copper treatment for Menkes disease should still be regarded as experimental. The development of more effective treatments must await a more precise delineation of the role which the Menkes protein plays in intracellular copper trafficking.
Subject(s)
Copper/therapeutic use , Histidine/therapeutic use , Menkes Kinky Hair Syndrome/drug therapy , Adolescent , Adult , Child , Drug Therapy, Combination , Follow-Up Studies , Humans , Male , Menkes Kinky Hair Syndrome/diagnostic imaging , RadiographySubject(s)
Acyl-CoA Dehydrogenases/deficiency , Muscular Diseases/enzymology , Scoliosis/enzymology , Adolescent , Female , Gas Chromatography-Mass Spectrometry , Glucose Tolerance Test , Growth Disorders/enzymology , Growth Disorders/genetics , Humans , Mitochondria, Muscle/enzymology , Muscle Hypotonia/enzymology , Muscle Hypotonia/genetics , Muscle, Skeletal/enzymology , Muscle, Skeletal/pathology , Muscular Diseases/genetics , Muscular Diseases/pathology , Respiratory Tract Diseases/enzymology , Respiratory Tract Diseases/genetics , Respiratory Tract Diseases/physiopathology , Scoliosis/geneticsSubject(s)
Bone Marrow Diseases/genetics , DNA, Mitochondrial/genetics , Gene Deletion , Pancreatic Diseases/genetics , Bone Marrow/pathology , Bone Marrow Diseases/complications , Cerebrospinal Fluid Proteins/metabolism , Child , DNA Probes , Humans , Male , Nucleic Acid Hybridization , Pancreatic Diseases/complications , Retinitis Pigmentosa/complications , Retinitis Pigmentosa/genetics , Syndrome , Vacuoles/pathologyABSTRACT
It is still an important duty for pediatricians to inform parents about infant nutrition. An effort to insure successful breastfeeding in newborns is particularly necessary in order to avoid the introduction of foreign proteins, especially in high risk children. Allergy prevention is thus instigated early on. If necessary, a hypoallergenic milk may be used. Recently, there has been great concern that a high content of dioxine in breast milk exists, higher than in infant formulas. However, no evidence of toxicity has been noticed to date in breast fed children due to dioxine. Therefore, because of the many advantages, breast feeding should still be recommended for the first 4-6 months. In the last few years infant formulas have been adapted to simulate breastmilk by supplementation with taurine, carnitine and nucleotides. Most recently, Omega-3-fatty acids, which are important constituents of membrane phospholipids in the nervous system and the retina, have been added. In infant nutrition there is a trend nowadays toward unconventional forms of nutrition. An exclusive "lactoovo-vegetable" diet is able to meet all the requirements of a growing child. The critical components of a vegetarian diet are iron, calcium, vitamin B12 and vitamin D. These few examples demonstrate how important a nutrition-committee could be in elaborating basic information for the pediatrician, which would be useful in his daily work.
Subject(s)
Breast Feeding , Infant Nutritional Physiological Phenomena , Dioxins/adverse effects , Dioxins/analysis , Humans , Infant , Infant, Newborn , Milk, Human/chemistry , Nutritional Requirements , Risk FactorsABSTRACT
The hyper-IgE syndrome is characterized clinically by recurrent staphylococcal abscesses of the skin, lungs and other sites from infancy. Affected patients also have a pruritic dermatitis that differs in character and distribution from lesions of atopic dermatitis. Most lack other signs of atopic disease, develop persistent pneumatoceles and have osteopenia. Laboratory abnormalities include the consistent presence of marked hyperimmunoglobulinemia E and eosinophilia of blood, sputum and tissues. They may have other inconsistent abnormalities of humoral and cellular immune responses and sometimes of phagocytic cell chemotactic responsiveness. Other clinical problems reported in such patients have included lymphomas, cryptococcal meningitis and cutaneous fungal disease. An 18-year-old male patient with a variant of the hyper-IgE syndrome, which he had acquired after a measles attack at the age of 5 years, suffered from recurrent ulcerative dermatitis and lymph node abscesses. Immunological investigation revealed an excessively elevated total serum IgE level (46,850 IU/ml), the presence of specific IgE to staphylococci, and quantitative and functional deficiency of IgG2. Skin and serological (radioallergosorbent) tests to inhalant and nutritive allergens were negative. Differentiation from atopic dermatitis should be made, because a long-term antistaphylococcal regime not only improves skin lesions but hinders the occurrence of lung abscesses and pneumatoceles.
Subject(s)
Abscess/diagnosis , Dermatitis, Atopic/diagnosis , Immunoglobulin E/analysis , Staphylococcal Skin Infections/diagnosis , Abscess/drug therapy , Abscess/pathology , Adolescent , Antibodies, Bacterial/analysis , Dermatitis, Atopic/pathology , Diagnosis, Differential , Eosinophilia/diagnosis , Floxacillin/administration & dosage , Floxacillin/therapeutic use , Humans , Immunoglobulin E/immunology , Male , Prognosis , Recurrence , Staphylococcal Skin Infections/drug therapy , Staphylococcal Skin Infections/pathology , Staphylococcus/immunology , SyndromeABSTRACT
The Dubowitz-syndrome, a rare, autosomal-recessive condition, was seen in a 6-year-old female patient. Verbal, fine motor, and social development were severely retarded. Behavioral disturbances, predominantly hyperactivity were apparent. Short stature of unknown origin became evident during infancy and early childhood. Atopic dermatitis and specific sensitivity to inhalant and nutritive allergens was found. A pattern of minor anomalies included inner epicanthic folds, hypertelorism, flat nasal bridge, globular nasal tip, coarse lips, and retrogenia as well as pes planovalgus, and a sacral dimple.
Subject(s)
Abnormalities, Multiple/genetics , Attention Deficit Disorder with Hyperactivity/genetics , Dermatitis, Atopic/genetics , Dwarfism/genetics , Facial Bones/abnormalities , Intellectual Disability/genetics , Allergens , Child, Preschool , Female , Humans , Intradermal Tests , SyndromeSubject(s)
Acetaminophen/therapeutic use , Fever/drug therapy , Ibuprofen/therapeutic use , Acetaminophen/administration & dosage , Body Temperature/drug effects , Child , Child, Preschool , Double-Blind Method , Drug Administration Schedule , Female , Humans , Ibuprofen/administration & dosage , Infant , MaleABSTRACT
Carbamyl phosphate synthetase (CPS) catalyses the synthesis of carbamyl-phosphate from ammonia and bicarbonate and is the first step in ureagenesis. The infant described in this report suffered from deficiency of this enzyme. The symptoms started on the 2nd day of life with tachycardia, apathy, irritability and metabolic alcalosis, on the 4th day coma and fits occurred due to hyperammonia (ammonia in the blood max 496 mumol/l, normally up to 150 in newborns). In hepatic tissue no activity of carbamyl phosphate synthetase could be measured (normal range 0.66-2.1 mumol/h/mg protein). Peritoneal dialysis was instituted, but the metabolic crisis could only be overcome by the following therapeutic measures: restriction of protein intake to 1.5 g/kg/d in part as a special aminoacid mixture, in part as breast milk; sufficient caloric supply (600-500 kJ/kg/d); sodium benzoate 350 mg/kg/d: arginine 2 mmol/kg/d respectively citrulline 350 mg/kg/d, and carnitine 150 mg/kg/d. By these procedures the exogenous and endogenous load of ammonia could be minimized. Electroencephalogram and mental development were normal. Acute metabolic crises with hyperammonia during catabolic states (infections) could be treated several times. At the age of 8 months, however, the patient died during such a crisis. This case shows that it is possible to achieve a normal psychomotor development in complete CPS-deficiency by adequate therapy. Catabolic states are difficult to manage.
Subject(s)
Amino Acids/administration & dosage , Ammonia/blood , Benzoates/administration & dosage , Carbamoyl-Phosphate Synthase (Ammonia)/deficiency , Dietary Proteins/administration & dosage , Fetal Growth Retardation/therapy , Arginine/administration & dosage , Benzoic Acid , Carnitine/administration & dosage , Citrulline/administration & dosage , Combined Modality Therapy , Female , Humans , Infant, Newborn , Male , PregnancyABSTRACT
Six patients with Menkes syndrome are described, who differ from patients with the classical form of Menkes syndrome because of their longer survival; some of them also exhibited a milder manifestation of symptoms. Based on the present data and a summary of seven case reports describing Menkes patients with long survival, it may be possible to divide these patients into two subgroups: one group of severely affected patients with long survival and another group of very mildly affected patients with late onset of symptoms. Perhaps only the latter represents a true subgroup of Menkes syndrome. The possible benefits of copper therapy are discussed.
Subject(s)
Brain Diseases, Metabolic , Menkes Kinky Hair Syndrome , Brain Diseases, Metabolic/genetics , Copper/therapeutic use , Humans , Infant, Newborn , Menkes Kinky Hair Syndrome/drug therapy , Menkes Kinky Hair Syndrome/genetics , PrognosisABSTRACT
For the understanding and interpretation of hypoglycemia it is important to know the many complex endocrine and metabolic regulations in the homoeostasis of blood glucose. Glucose-absorption, distribution and availability, glycolysis, production and utilization of glycogen as well as gluconeogenesis are important steps of this homoeostasis, and hypoglycemia always reflects a disturbance in it. When blood glucose is low the availability of energy for the brain is decreased if no alternative energy sources like lactate or ketones are provided. Hypoglycemia is more often in the neonatal period than in later childhood. The causes can be divided into different groups according to pathogenetic mechanisms. Within each group again many singular defects are known. Fructose-1,6-diphosphatase deficiency, hereditary fructose intolerance, glycogenosis type I and so called "ketotic hypoglycemia" are given as examples to elucidate special clinical and biochemical aspects of inborn errors of carbohydrate metabolism.
Subject(s)
Blood Glucose/metabolism , Carbohydrate Metabolism, Inborn Errors/genetics , Gluconeogenesis , Glycolysis , Hypoglycemia/genetics , Carbohydrate Metabolism, Inborn Errors/physiopathology , Child , Enzymes/deficiency , Humans , Hypoglycemia/physiopathologyABSTRACT
Menkes' disease is a rare X-linked recessive inherited disorder of copper metabolism characterized by neurodegeneration, peculiar hair, and early death. The symptoms can be attributed to decreased activity of copper-dependent enzymes, but treatment with copper has so far failed to influence the course of the disease. We present the case of an 8.5-year-old boy, whom we treated alternately with intramuscular copper-histidine and oral D-penicillamine and who showed an extraordinary mild form of Menkes' disease. In contrast to his untreated maternal uncle, this patient had normal growth and intellectual development, but showed marked ataxia and slight speech difficulties. We suggest that parenteral copper-histidine supplemented by oral D-penicillamine may be of benefit to early-treated patients with Menkes' disease.
Subject(s)
Brain Diseases, Metabolic/drug therapy , Copper/therapeutic use , Menkes Kinky Hair Syndrome/drug therapy , Penicillamine/therapeutic use , Body Fluids/analysis , Brain/pathology , Copper/analysis , Drug Therapy, Combination , Electroencephalography , Genes, Recessive , Histidine/therapeutic use , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Male , Menkes Kinky Hair Syndrome/genetics , X ChromosomeABSTRACT
BCG osteitis is a rare complication after vaccination in the newborn. On the basis of various, not yet fully known mechanisms, an increase in the number of cases is nevertheless possible. In the period 1980-1985 the authors recorded 6 instances of BCG osteitis. The clinical findings and diagnostic criteria are described. The incidence, pathogenesis and therapy of the disease are discussed.
Subject(s)
BCG Vaccine/adverse effects , Osteomyelitis/etiology , Antitubercular Agents/therapeutic use , BCG Vaccine/therapeutic use , Child, Preschool , Female , Humans , Infant , Male , Osteomyelitis/diagnostic imaging , Osteomyelitis/drug therapy , Radiography , Tuberculosis, Pulmonary/prevention & controlABSTRACT
Antipyretic effect, tolerability, and acceptance of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) drops were tested within the scope of an open study including a total of 111 children with fever of various etiology; two investigational centers participated in this study. The initial mean rectal temperature averaged 39.3 degrees C. The dosage of suprofen drops depended upon the patient's body weight and age; the drug was administered up to q.i.d., for 4 days at the longest. Body temperature, pulse rate, and respiratory rate were recorded prior to administration and 1/2, 1, 1 1/2, 2, 3, 4, 5 and 6 h after first administration of the drug. The antipyretic effect of the treatment was appreciated good in 89% of the cases. Reduction in temperature was statistically significant at all rating times after first administration of the drops as compared with the initial values. Adverse drug experiences such as vomiting and loose stools were seen in only 5 cases. The tolerability was considered good in 96% and the acceptance in 94% of the cases.
Subject(s)
Fever/drug therapy , Phenylpropionates/therapeutic use , Suprofen/therapeutic use , Body Temperature/drug effects , Child , Child, Preschool , Female , Humans , Infant , Kinetics , Male , Pulse/drug effects , Respiration/drug effects , Suprofen/adverse effectsABSTRACT
On routine smears of blood and bone marrow of four patients with GM1 gangliosidosis type I, eosinophil granulocytes were unusually pale and contained faintly stained, unevenly spaced granules some of which were larger than normal and had abnormal ultrastructural appearance. The anomaly may represent a hitherto overlooked but easily obtainable diagnostic marker.