1/13. A unique case of derangement of vitamin B12 metabolism.The case is described of a child, age 6 1/2 years, with retarded mental development, mild neurological signs and abnormal metabolism of sulphur-containing amino acids and methylmalonate, due to an inborn error in the formation of vitamin B12 coenzymes. The patient was treated for almost three years with hydroxycobalamin, folic acid, pyridoxine and choline. Though physical growth was normal, she continued to demonstrate a moderate degree of mental retardation. A brother of the patient died at the age of 5 years, probably of a similar, but undiagnosed, disorder. As far as we are aware there are only four other reported cases similar to the case described here. Two of these patients died and in other other two the defect was so mild that no treatment was necessary and who, in fact, showed appreciable improvement during the follow-up period, which to date amounts to 3 years and 3 months. For reasons detailed in the discussion, it is suggested that the diagnosis of homocystinuria is not complete until studies of folate and vitamin B12 metabolism are undertaken at the same time, so as to identify the metabolic defect(s) responsible for the condition.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/13. Impact of estrogen replacement therapy in a male with congenital aromatase deficiency caused by a novel mutation in the CYP19 gene.Recent reports of the impact of estrogen receptor alpha and aromatase deficiency have shed new light on the importance of estrogen for bone formation in man. We describe a novel mutation of the CYP19 gene in a 27-yr-old homozygous male of consanguinous parents. A C to A substitution in intron V, at position -3 of the splicing acceptor site before exon VI of the CYP19 gene, is the likely cause of loss of aromatase activity. The mRNA of the patient leads to a frameshift and a premature stop codon 8 nucleotides downstream the end of exon V. Both parents were shown to be heterozygous for the same mutation. Apart from genua valga, kyphoscoliosis, and pectus carniatus, the physical examination was normal including secondary male characteristics with normal testicular size. To substitute for the deficiency, the patient was treated with 50 micro g transdermal estradiol twice weekly for 3 months, followed by 25 micro g twice weekly. After 6 months estrogen levels (<20 at baseline and 45 pg/ml at 6 months; normal range, 10-50) and estrone levels (17 and 34 ng/ml; normal range, 30-85) had normalized. Bone maturation progressed and the initially unfused carpal and phalangeal epiphyses began to close within 3 months and were almost completely closed after 6 months. The bone age, assessed by roentgenographic standards for bone development by Gruelich and Pyle, was 16.5 at baseline and 18-18.5 yr after 6 months of treatment. bone density of the distal radius (left), assessed by quantitative computed tomography, increased from 52 to 83 mg/cm(3) (normal range, 120-160) and bone mineral density of the lumbar spine, assessed by dual-energy x-ray-absorptiometry, increased from 0.971 to 1.043 g/cm(2) (normal range, >1.150). osteocalcin as a bone formation parameter increased from 13 to 52 micro g/l (normal range, 24-70) and aminoterminal collagen type i telopeptide as a bone resorption parameter increased from 62.9 to 92.4 nmol/mmol creatinine (normal range, 5-54). semen analysis revealed oligoazoospermia (17.4 million/ml; normal >20) at baseline. After 3 months of treatment, the sperm count increased (23.1 million/ml) and decreased rapidly (1.1 million/ml) during the following 3 months. The sperm motility was reduced at baseline and decreased further during treatment. Area under the curve of insulin, c-peptide, and blood glucose levels during oral glucose tolerance test decreased after 6 months (insulin: 277 vs. 139 micro U/ml.h; c-peptide 52 vs. 15 ng/m.h; area under the curve glucose: 17316 vs. 12780 mg/d.min). triglycerides (268 vs. 261 mmol/liter) and total cholesterol levels (176 vs. 198 mmol/liter) did not change significantly, but the low-density lipoprotein/high-density lipoprotein ratio decreased from 5.37 to 3.56 and lipoprotein (a) increased from 19.9 to 60.0 mg/dl (normal range, <30). In this rare incidence of estrogen deficiency, estrogen replacement demonstrated its importance for bone mineralization and maturation and glucose metabolism in a male carrying a novel mutation in the CYP19 gene.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
3/13. Congenital methemoglobinemia: a rare cause of cyanosis in the newborn--a case report.cyanosis is a physical finding that can occur at any age but presents the greatest challenge when it occurs in the newborn. The cause is multiple, and it usually represents an ominous sign, especially when it occurs in association with neonatal sepsis, cyanotic congenital heart disease, and airway abnormalities. cyanosis caused by abnormal forms of hemoglobin can also be life-threatening, and early recognition is mandatory to prevent unnecessary investigations and delay in management. Abnormal hemoglobin, such as hemoglobin m, is traditionally discovered by electrophoresis, so the newborn screen, which is mandatory in several states, is a useful tool for the diagnosis. Although acquired methemoglobinemia, caused by environmental oxidizing agents, is common, congenital deficiency of the innate reducing enzyme is so rare that only a few cases are documented in the medical literature around the world. We present a neonate with cyanosis as a result of congenital deficiency of the reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase enzyme. This infant was found to be blue at a routine newborn follow-up visit. sepsis, structural congenital heart disease, prenatal administration, and ingestion of oxidant dyes were excluded as a cause of the cyanosis by history and appropriate tests. Chocolate discoloration of arterial blood provided a clue to the diagnosis. A normal newborn screen and hemoglobin electrophoresis made the diagnosis of hemoglobin m unlikely as the cause of the methemoglobinemia (Hb A 59.4%, A2 1.8%, and F 38.8%). Red blood cell enzyme activity and dna analysis revealed a homozygous form of the cytochrome b5 reductase enzyme deficiency. He responded very well to daily methylene blue and ascorbic acid administration, and he has normal growth and developmental parameters, although he shows an exaggerated increase in his methemoglobin level with minor oxidant stress such as diarrhea.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
4/13. Acute metabolic decompensation in an adult patient with isovaleric acidemia.Isovaleric acidemia is a rare autosomal recessive inborn error of leucine catabolism caused by deficiency of isovaleryl coenzyme a dehydrogenase. This enzymatic deficiency leads to severe metabolic derangement, manifested clinically as vomiting, dehydration, and acidosis progressing to seizures, coma, and death. The two phenotypic expressions are the acute severe and the chronic intermittent form. The acute severe phenotype typically results in death during early infancy, whereas patients with the chronic intermittent form are asymptomatic at baseline but have episodes of acute metabolic decompensation, usually in the setting of infection, physical exertion, or ingestion of protein-rich food. This case illustrates how inborn errors of metabolism resulting in organic acidemia can be manifested in adults and why the internist needs to be aware of them.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
5/13. Autistic-like findings associated with a urea cycle disorder in a 4-year-old girl.A 4-year-old girl presented at our clinic with autistic-like symptoms, aggressivity and occasional hyperactivity. She had no history of neurologic or physical symptoms. Her condition was diagnosed as pervasive developmental disorder not otherwise specified, according to the criteria of the diagnostic and statistical manual of mental disorders, fourth edition (DSM-IV). She received pharmacologic (thioridazine), educational and speech therapy. During this process, a urea cycle disorder was also identified, namely, ornithine transcarbamylase deficiency and arginase deficiency, because of the high level of ammonia in the patient's bloodstream, the high level of organic acids in the 24-hour urine collection and the constant presence of slow multifocal epileptic discharges on the electroencephalograms. The patient's protein intake was restricted, and she was treated with sodium benzoate and arginine. After 1 year of treatment, the autistic-like findings and hyperactivity were no longer apparent.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
6/13. Corticosterone methyloxydase deficiency type II in a Croatian girl.This is a brief case report on a four-month-old girl who was admitted for failure to thrive and moderate dehydration. On admission she was mildly dehydrated and undernourished but with otherwise normal physical findings. Laboratory investigation disclosed mild but constant hyponatremia and hyperkalemia, very high plasma renin activity (greater than 900 ng/mL per hour) and low plasma aldosterone concentration (2.5 ng/dL). The plasma 18-hydroxycorticosterone (18-OH-B) was very high (1,682 ng/dL), producing thus an abnormally elevated 18-OH-B to aldosterone ratio of 542 (normally 6.3 /- 3.6). The diagnosis of corticosterone methyloxydase deficiency type II was made, and the administration of fluorohydrocortisone resulted in rapid weight gain with normalization of blood electrolytes and gradual decrease in plasma renin activity. A very efficient catch-up growth resulted in normal body weight and length at the age of 2 years. This is the first well documented case of the disease in the population of yugoslavia.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
7/13. Methylcrotonyl-CoA carboxylase (MCC) deficiency associated with severe muscle pain and physical disability in an adult.We present a patient with methylcrotonyl-CoA carboxylase (MCC) deficiency (McKusick 210200) who suffered from severe muscle pain and physical disability, and propose that this disorder be considered in the differential diagnosis of adult patients presenting with muscle pain and weakness.- - - - - - - - - - ranking = 5keywords = physical (Clic here for more details about this article) |
8/13. Papillary carcinoma of the thyroid arising from dyshormonogenetic goiter.A case of thyroid papillary carcinoma associated with dyshormonogenetic goiter is reported. The patient, a 35-year-old male, has been on thyroid hormone therapy since the age of three because of familial dyshormonogenetic goiter. He developed a distinct tumor in the right lobe, which was suggestive of carcinoma upon physical as well as ultrasonographic examination. Total thyroidectomy was performed, since a frozen section disclosed a focus of papillary carcinoma and the possibility of future development of further malignancy in any remaining thyroid tissue was considered. The patient is currently well with complete thyroid hormone supplementation one and a half years after the operation.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
9/13. sialic acid storage disease with sialuria: clinical and biochemical features in the severe infantile type.Two unrelated infants with a new disorder characterized biochemically by elevated levels of free sialic acid in urine, serum, and cell lysates have exhibited severe mental and physical impairments since the early weeks of life. Three other biochemically diagnosed cases and two possible cases from the earlier literature are reviewed to delineate this condition. Clinical features including sparse, white hair, coarse facies, hepatosplenomegaly, profound inactivity, diarrhea, and anemia permit early diagnosis of this neurovisceral storage disease. Osseous stippling may be present and clear vacuoles may be demonstrated in lymphocytes and cultured fibroblasts. The course is one of relentless deterioration with death in early childhood. Specific diagnosis depends on demonstration of elevated free sialic acid in urine and cell lysates.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
10/13. A case of benign familial hyperphosphatasemia of intestinal origin.We recently encountered a case of hyperphosphatasemia, in which > 90% of serum alkaline phosphatase (ALP) was of intestinal origin. The patient, a 51-year-old man, was found to have hyperphosphatasemia (2,341 U/L) during a routine medical check-up. All other laboratory tests and physical findings were normal. The agarose gel electrophoresis pattern of the patient's serum ALP was identical to that of common intestinal ALP from healthy adults, and only a single band of intestinal ALP was detected by immunoaffinity electrophoresis. In addition, 89% of total ALP was defined as intestinal ALP by an immunoprecipitation method. The molecular mass of the ALP was 154 kDa, almost identical with that of adult duodenal ALP. Analysis of the sugar chain structure showed an increased la fraction (74%) compared with adult duodenal ALP. Genealogical study revealed that two persons in the 5 members of the proband's family had hyperphosphatasemia of intestinal origin, indicating possible autosomal dominant inheritance.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
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