Complex disorder of neuronal migration in an infant with possible congenital cytomegalovirus infection.

A ten-months-old girl was evaluated for developmental delay, increased muscle tone and seizures. CT and MRI revealed un uncommon combination of two different manifestations of neuronal migration disturbance: agyria/pachygyria and subcortical laminar heterotopia ("double cortex" syndrome). The occurrence of these two manifestations of neuronal migration dosorders in the same individual is quite unusual. The possible pathogenesis of such a complex disorder could probably be established only by histologic examination of the brain. A positive serologic reaction for cytomegalovirus in the infant at the age of 11 months and in the mother suggested but did not prove the cytomegalovirus infection in early gestation as the cause of the disorder.

[Dynamic mutations--a newly detected category of mutations which is the basis for certain neurologic diseases]. / Dinamicne mutacije--novootkrivena kategorija mutacija osnova su za nekoliko neuroloskih bolesti.

This review offers some basic information on the discovery of a new type of mutations being the cause of some significant neurologic diseases: myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type 1, spinobulbar pallido-louysian muscular atrophy, fragile X syndrome and some other, up to a total of ten entities. The basis of the so-called dynamic mutations is an abnormal multiplication of a trinucleotide producing sequences of several hundreds or even thousands of identical copies in the respective gene. The result is designated as expanded or amplified trinucleotide (or triplet) repeat. These sequences are not stable, but increase (or exceptionally decrease) in length during cell multiplication in successive generations. They segregate within families with the affected members, demonstrating a significant correlation between the length of the repeat sequence, the severity of the pathologic phenotype and an inverse correlation with the age at the clinical manifestation of the disease. Thus, at least, a formal explanation for the anticipation phenomenon of the age at which the disease is manifested within a family is offered. The importance of the discovery of dynamic mutations lies in the possibility for more precise and reliable genetic counselling. The discovery has opened a lot of new questions giving a new impetus for intensive research.

[Homocystinuria: case reports with a note on hyperhomocysteinemia as a risk factor for the early onset of vascular disease]. / Homocistinurija: prikaz bolesnika uz osvrt na hiperhomocisteinemiju kao faktor rizika za ranu pojavu bolesti krvnih zila.

Two brothers and a sister suffering from homocystinuria caused by cystathionine beta-synthase deficiency and the possibilities of treatment are presented. Possible clinical variability, the necessity for early diagnosis and the importance of hyperhomocysteinemia as a risk factor for early-onset vascular disease are discussed.

Haplotype distribution and mutations at the PAH locus in Croatia.

Restriction fragment length polymorphism (RFLP) haplotypes and mutations at the phenylalanine hydroxylase (PAH) locus have been studied in 25 unrelated families from Croatia. The results of RFLP analysis demonstrated that 80% of the mutant alleles were associated with three haplotypes (1, 2 and 4). Eight mutations were detected on the background of six mutant haplotypes, comprising 68% of phenylketonuria (PKU) alleles in Croatia. The mutation in codon 408 was most frequent, as was the haplotype 2 allele with which it was associated. These data are in accordance with formerly published population genetic analyses at the PAH locus, and with studies revealing the molecular basis of the phenotypic heterogeneity of PKU. The codon 281 mutation was more frequent in Croatia than previously observed in other populations.

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.

[Care of children during wartime]. / Osobitosti zastite djece u ratu.

Children represent the most vulnerable segment of the civilian population during wartime. Besides the direct effects of weapons and destructions during warfare, children are particularly prone to other forms of damage; extensive disruptions in the environment of the individual child are setting the stage for an increased appearance of infectious diseases, and long term limitations of adequate nutrition are causing various forms of malnutrition and of nutritional deficiencies. The consecutive decrease of general resistance against infectious diseases is an important dispositional factor in the pathogenesis of recurrent and chronic infections. Most severe, far reaching and often irreversible damages are those of mental health of children, sometimes lasting for the whole lifetime of the individual. Some of the most simple but effective preventive measures to alleviate the suffering of children during wartime, accessible to every health worker are briefly reviewed.

Immunological aspects of progeria (Hutchinson-Gilford syndrome) in a 15-month-old child.

A thorough analysis of the immunological status was conducted in a 15-month-old child with progeria (Hutchinson-Gilford syndrome). Total leukocyte and neutrophil counts were slightly increased, and monocytes were decreased. Percentage and numbers of CD4+ cells in the blood were mildly decreased as well as the CD4/CD8 cell ratio. CD20 (B-cell marker) bearing cells and cells bearing Ia-antigens were increased, as well as CD16 and CD56 marker-bearing cells (natural-killer cells, NK). Lymphocyte proliferation upon stimulation with phytohaemagglutinin and purified protein derivative were decreased, and with pokeweed mitogen increased. NK cell activity appeared increased, particularly at lower effector: target cell ratios.

[Inborn metabolic errors of urea cycle synthesis. Present possibilities of treatment]. / Prirodene greske u metabolickom ciklusu sinteze ureje. Suvremene mogucnosti lijecenja.

The case history of an infant with congenital hyperammonaemia due to inherited ornithine-transcarbamylase deficiency is presented together with some basic data on his family. The metabolic cycle of urea synthesis is delineated with its enzymes and the possible inherited defects. The differential diagnosis of hyperammonaemia in the newborn infant is given. The successful contemporary method of therapy of urea cycle disorders is presented.

Screening of newborns for congenital hypothyroidism in Croatia--organization and first results.

In 1985 a newborn screening programme for the detection of congenital hypothyreosis was introduced in Croatia in addition to the already existing one for phenylketonuria. The paper delineates the organization of the screening programme, the method used, and the first results. Clinical manifestations, somatic and mental development, as well as laboratory findings of the first eleven children with congenial hypothyroidism detected by the screening programme and followed-up regularly are presented in more detail.

'Cryptic' form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in the Yugoslav population.

Five individuals with the asymptomatic, 'non-classical', 'cryptic' form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OH) deficiency from 5 unrelated families were discovered during hormonal studies and HLA-typing performed in a series of 24 families with CAH due to 21-OH deficiency. Four of the 5 individuals with the 'cryptic' form of CAH belong to families where the index case was a patient with the classical form of CAH due to 21-OH deficiency. The fifth one originated from a family where the index case was a girl with the 'non-classical', 'late-onset' form of the disease. All the 5 individuals had no clinical symptoms in spite of clearcut biochemical signs of 21-OH deficiency: increased 17-OH-progesterone (17-OHP), dehydroepiandrosterone and androstenedione levels, particularly after ACTH-stimulation. The 17-OHP response upon ACTH stimulation of heterozygotes for this 'non-classical' form of 21-OH deficiency did not differ from the response of heterozygous individuals for the classical form of the disease. The results of this study confirm the hypothesis that individuals with the 'cryptic' form of CAH due to 21-OH deficiency are genetic compounds bearing one allele for the severe, classical form, and on the homologous locus, another one for the mild 'non-classical' form of CAH due to 21-OH deficiency. Their genotype was 21-OH severe/21-OH mild.(ABSTRACT TRUNCATED AT 250 WORDS)

Coincidence of pseudohypoaldosteronism with gluten-enteropathy.

This is a 21-month-old boy with pseudohypoaldosteronism (PHA) in coincidence with celiac disease. The diagnosis of PHA was made on the basis of hyponatremia, hyperkalemia and large urinary salt losses, as well as high renin activity and aldosterone levels and increased urinary plasma aldosterone. Whereas mineralocorticoid therapy was ineffective, salt therapy has proven successful. The patient's HLA type was found to be characteristic of gluten-enteropathy (A1, B8, DR3). The combination of PHA and celiac disease has not yet been described and is probably a coincidence. However, it is suggested that other PHA patients be typed in order to investigate the segregation between HLA type, PHA and celiac disease.

Acute polyneuropathy with severe generalized rigidity in a child aged 16 months. Preliminary report.

A case of acute severe generalized muscle rigidity in a 16-month-old child is described. The arm flexors and leg extensors were the most severely involved, with all stretch reflexes absent. Motor conduction velocities on the arms and legs were very slow and nerve potentials were not elicited. The rigidity and electromyographically recorded spontaneous activity almost disappeared on carbamazepine treatment, with nerve conduction velocities remaining unchanged.