Quantitative amino acid analysis using a Beckman system gold HPLC 126AA analyzer.

BACKGROUND: The Beckman 6300/7300 analyzer, which was widely used for amino acid (AA) analysis, is no longer commercially available. METHODS: To set up an affordable AA analysis program, a Beckman system gold HPLC 126AA analyzer and Pickering Laboratories reagents were used. Two quantitative AA analysis programs were developed. One was an 18-min short program quantitating seven AAs from plasma and dried blood spots (DBS) specimens using Lithium eluents Li-365 and Li-375 at 70 degrees C column temperature. The short program could be used for diagnosis and follow-up dietary management for phenylketonuria (PKU), maple syrup urine disease (MSUD), tyrosinemia and homocystinuria patients. The second program was a 118-min long AA screening panel quantitating 40 AAs using Lithium eluents Li-275, Li-365 and Li-375 at 32, 48 and 72 degrees C column temperatures from plasma and urine specimens. RESULTS: The values obtained from DBS specimens were in good agreement with certified results from the Centers for Disease Control and Prevention. The values obtained from plasma and urine samples were in good correlation with those obtained from Beckman 6300 analyzer (0.9076 < or = r < or = 0.999). CONCLUSIONS: Amino acid quantitation from physiological samples using a Beckman 126AA Analyzer and Pickering Laboratories reagents was useful for clinical diagnosis and monitoring of aminoacidopathies.

Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD gene.

Malonyl CoA decarboxylase (MCD) is an enzyme involved in the metabolism of fatty acids synthesis. Based on reports of MCD deficiency, this enzyme is particular important in muscle and brain metabolism. Mutations in the MCD gene result in a deficiency of MCD activity, that lead to psychomotor retardation, cardiomyopathy and neonatal death. To date however, only a few patients have been reported with defects in MCD. We report here studies of a patient with MCD deficiency, who presented with hypotonia, cardiomyopathy and psychomotor retardation. DNA sequencing of MCD revealed a homozygous intronic mutation, specifically a -5 C to T transition near the acceptor site for exon 3. RT-PCR amplification of exons 2 and 3 revealed that although mRNA from a normal control sample yielded one major DNA band, the mutant mRNA sample resulted in two distinct DNA fragments. Sequencing of the patient's two RT-PCR products revealed that the larger molecular weight fragments contained exons 2 and 3 as well as the intervening intronic sequence. The smaller size band from the patient contained the properly spliced exons, similar to the normal control. Western blotting analysis of the expressed protein showed only a faint band in the patient sample in contrast to a robust band in the control. In addition, the enzyme activity of the mutant protein was lower than that of the control protein. The data indicate that homozygous mutation in intron 2 disrupt normal splicing of the gene, leading to lower expression of the MCD protein and MCD deficiency.

New multiple congenital anomalies/mental retardation syndrome with cardio-facio-cutaneous involvement--the CFC syndrome.

Eight patients (4 males, 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which was designated the Cardio-Facio-Cutaneous (CFC) syndrome and which includes congenital heart defects, characteristic facial appearance, ectodermal abnormalities, and growth failure. Cardiac defects were variable, the most common being pulmonic stenosis and atrial septal defect. Typical facial characteristics were high forehead with bitemporal constriction, hypoplasia of supraorbital ridges, antimongoloid slant of palpebral fissures, depressed bridge of nose, and posteriorly angulated ears with prominent helices. The hair was usually sparse and friable. Skin changes varied from patchy hyperkeratosis to a severe generalized ichthyosis-like condition. All cases were sporadic in occurrence, there was no family history of consanguinity, and chromosomes were normal. Although presumed to be genetic, the cause of the CFC syndrome remains unknown.

Newborn hypothyroid screening. The private sector.

Newborn hypothyroid screening in four private hospitals was prospectively evaluated and compared with a state screening program. During 1982 the hospitals screened a total of 10,786 infants compared with 47,525 by the state. Eight cases of primary hypothyroidism were confirmed by the state, for an incidence of one in 5,941. No cases were detected by the hospital programs. The cost for all infants screened in the private hospitals was 51.5 times more than the total cost of the state program, yet the state screened 4.4 times more infants.

Patients in a clinic for children with multiple handicaps: a retrospective diagnostic evaluation.

This study illustrates the effectiveness of an outpatient facility in evaluating patients with a variety of handicapping disorders. A multidisciplinary approach, such as the one used in the Child Study Clinic, is the most effective and most efficient mode of evaluating handicapped children, though hospitalization is occasionally required to further evaluate such complicated problems. Every child with mental retardation, birth defects, or multiple handicaps requires a thorough evaluation for the purposes of diagnosis, treatment, and the prescription of long-term educational and occupational goals. Family history often indicates the need for genetic counseling.

Familial gynecomastia without hypogonadism.

A family, six members of which had gynecomastia without hypogonadism, is presented. Endocrine studies failed to show the specific nature of breast enlargement in the patients. Chromosomal studies using peripheral leukocytes resulted in normal findings. In one of the patients, chromosomal studies were done using breast tissue and fascia, and again no abnormalities could be detected. The mode of inheritance may be autosoma dominant with sex limitations; however, X-linked inheritance cannot be ruled out.

Chromosome variants in children with psychiatric disorders.

The authors studied the frequency of chromosome variants in 48 hospitalized children with psychiatric diagnoses (study group) in comparison with 10 hospitalized children with nonpsychiatric diagnoses (control group) and the results of three surveys of newborn children. They found that the frequency of variants in their study group was elevated in comparison with their control group and with the newborn surveys.

The radial dysplasia/imperforate anus/vertebral anomalies syndrome (the VATER association): Developmental aspects and eye findings.

The developmental evaluations of four children of different age groups with radial dysplasia/imperforate anus/vertebral anomalies syndrome are presented. These show that although the gross motor behavior is significantly delayed, intelligence, language, and social development are within normal range. Therefore, the patients with this syndrome merit every effort toward rehabilitation. Three of the patients discussed have ophthalmological abnormalities, in addition to their major malformations. It may be that congenital eye defects are another component of this syndrome of morphogenesis.

Hereditary defect of the sacrum.

A family in which both the mother and two of her daughters had partial agenesis of the sacrum and coccygeal bones is presented. Further studies demonstrate a neurogenic bladder and a presacral mass in the 4-year-old girl who had severe urinary incontinence. The mode of inheritance in this entity may be x-linked dominant as has been suggested. Previously by Cohn and Bay-Nielsen (1969). The gene may act as a lethal factors in hemizygous males. A brief review of the literature showed a remarkable paucity of reports on the hereditary aspects of sacrococcygeal defects in man. It is concluded that this may be misleading, since the true incidence of hereditary sacroccygeal deformities can not possibly be established until family members of the probands are also examined radiologically.