Folic acid: miscarriages, anomalies, thromboses, cancers.

Folic acid is an essential micronutrient that merits special attention. In spite of plentiful sources in a balanced diet, recent data indicate that folic acid intake of many persons has long been inadequate. To some degree, this is due to destruction of folic acid by storage and processing of foodstuffs and to dietary practices that vary from recommendations. However, the common hereditary thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) imposes an increased folic acid requirement which, if not met, may result in recurrent early pregnancy loss, anomalous progeny, thrombotic disorders, and cancers. There are recent reports that folic acid metabolism is also altered by other hereditary variations of MTHFR and other enzymes involved in folic acid metabolism. Optimal management requires dietary guidance and, for many patients, folate supplements. Caution is required because mandated folate fortification of grain products may produce levels that are inadequate for some patients and excessive for others. Laboratory tests for red cell folate and serum homocysteine are valuable adjuncts.

Counseling your patient about heritable breast cancer.

The baseline frequency of breast cancer increases after age 30 from about 1% to about 10% by age 90. Breast cancer gene mutations cause much higher risks. Risks are nearly as high if two or more first-degree relatives (mother, sisters) had breast cancer when less than 50 years old. Risks are also elevated by occurrence of breast cancer at young ages in second-degree relatives (grandmothers, aunts). Certain rare syndromes are also associated with higher risks of breast cancer. Genetic testing for breast cancer gene mutations and for some of the syndromes is available but mutational heterogeneity limits its usefulness. Counseling about these aspects of breast cancer should be within the purview of any physician who manages patients who are at risk. The medical geneticist can assist in recognizing rare syndromes, identifying patients whose risks merit consideration of genetic testing or of prophylactic surgery, and in counseling in complex cases.

Genetics, aging, and the heart.

Heart disease remains the most frequent cause of death in the general population and is intimately related to aging. Either extreme premature aging or marked longevity may be monogenic, but in most humans aging is a complex polygenic phenomenon. Hypercholesterolemia and hypertension are important factors. Cardiac amyloidosis and vascular elastin degradation may be separate factors. Humans with the greatest longevity are relatively refractory to atherosclerosis. Frequencies of heart deaths among relatives of a heart-death proband without dyslipoproteinemia conform to expectations of a polygenic trait. Careful, attentive medical management of major environmental factors and of heart senescence can result in more successful aging.

Nutritional disorders in a concentration camp.

OBJECTIVE: Observations on nutritional disorders were made by a physician inmate in a concentration camp before and during the Great Starvation in China. METHODS/RESULTS: Based on therapeutic response, many unique abnormalities should be considered as a part of clinical picture of malnutrition, such as mucocutaneous pigmentation, nail layering phenomena and intranail hemorrhage, palmar/plantar fissures, vegetative system crisis, a avitaminostic fevers, multiple premature beats, and enlargement of cartilage, lymph nodes, and submandibular glands. DISCUSSION: Thiamin deficiency should be also considered as one, if not the only, etiologic factor of several common disorders, including submandibular gland cyst, Baker's cyst, stenosing tenosynovitis, direct inguinal hernia, among others.

Congenital universal muscular hypoplasia: evidence for autosomal recessive inheritance.

Congenital universal muscular hypoplasia has been confused with similar diseases in the past. Evidence presented in this paper distinguishes this disorder from other phenotypically similar ones and indicates that it is inherited as an autosomal recessive disorder.

Genetic considerations in human cancer incidence.

Analysis by the methods of genetic demography can offer plausible explanations for the unusual distribution of cancer in an area of high incidence. The important demographic characteristics include inbreeding, founder effect, and racial admixture. Inbreeding would elevate cancer incidence if autosomal recessive genes played a role in cancer etiology. Founder effect would limit this phenomenon to those recessive genes observed in the founding group and result in a cancer spectrum different from that of the surrounding populations. The preference of a racially admixed group for classification as white could result in an excess of cancer patients being classified as white. The population groups in southern Louisiana typify the kind of "human genetics laboratory" that inbred groups offer to investigators of the genetic aspects of cancer.

Tumoral calcinosis and Engelmann disease.

Four cases of Engelmann disease were observed in a dominant inheritance pattern in a family of St. Landry Mulattoes. In the youngest sibship, one of the cases also had tumoral calcinosis. Another sib had only tumoral calcinosis, though some findings suggested that this sib may also have had Engelmann disease. All 3 of the younger sibs had snow-capped teeth. It is suggested by this family that snow-capped teeth may be part of the syndrome of Engelmann disease.

New syndromes of mental retardation.

During a survey of a selected group of residents of an institution for the mentally retarded, four previously undescribed syndromes were found. They were characterized as follows: cerebral maldevelopment, dwarfism and cataracts (autosomal recessive inheritance); cerebral maldevelopment, dwarfism and facial osteoproliferation (autosomal recessive inheritance); cerebral maldevelopment and colobomata (autosomal recessive inheritance); and cerebral maldevelopment and acrocephaly (X-linked recessive inheritance).

Acrocephalosyndactyly and partial trisomy 6.

A partial trisomy of the long arm of chromosome 6 was found in an infant with acrocephalosyndactyly (not Apert acrocephalosyndactyly). The mother had a balanced translocation involving the long arms of chromosomes 6 and 10. Other reports of similar aberrations are reviewed.

Silent hemoglobin alpha genes in apes: potential source of thalassemia.

Small quantities of unusual hemoglobins were found in 1 of 37 chimpanzees and 2 of 6 gorillas. In each genus these hemoglobins contain unique alpha chains that differ from the ordinary by eight to nine scattered amino acid changes. The unusual chains arise from a hitherto undetected hemoglobin (3)alpha locus. No (3)alpha products are found in most apes; accordingly, (3)alpha is considered synthetically inactive in all but a few reversion mutants. Indirect evidence that the inactive (3)alpha locus is juxtaposed to an active alpha locus together with the supposition that (3)alpha exists in man provides a setting wherein thalassemia might be produced by nonhomologous recombination between two loci.