Differences in screening and confirmatory thyroid profiles in congenital hypothyroid subtypes: implications for missed cases.

Subtypes of primary congenital hypothyroidism (CHT) showed different degrees of impairment of thyroid function at screening and confirmation. Patients with athyrosis showed the greatest impairment with mean value for screening 1-thyroxine (ScrT4) of 2.73 micrograms/dl (p < 0.0001 vs E group), screening thyroid-stimulating hormone (ScrTSH) of 327.6 microIU/ml (p < 0.0001 vs E group), confirmatory L-thyroxine (ConT4) of 1.21 micrograms/dl (p < 0.0001 vs E group), and confirmatory thyroid-stimulating hormone (ConTSH) of 572 microIU/ml (p < 0.0001 vs E group). Infants with dysgenetic ectopic thyroids (E group) showed the best preservation of function with mean values for ScrT4 of 6.0 micrograms/dl, ScrTSH of 229 microIU/ml, ConT4 of 6.23 micrograms/dl, and ConTSH of 324.8 microIU/ml. Generally, intermediate mean values were found for infants with normal or goitrous thyroids with values for ScrT4 of 4.26 micrograms/dl, ScrTSH of 205 microIU/ml, ConT4 of 3.21 micrograms/dl, and ConTSH of 428 microIU/ml. The risk for CHT being missed appeared to be greatest in patients with dysgenetic ectopic thyroids with the mean difference between ScrT4 and the L-thyroxine cutoff value (ScrT4Diff) being -2.2 micrograms/dl; five cases fell within 0.5 microgram/dl of the cutoff. The risk was least in infants with athyrosis with ScrT4Diff of -4.64 micrograms/dl (p < 0.0001 vs E group); no cases were within 1 microgram/dl of missing the cutoff. For infants with normal or goitrous thyroids ScrT4Diff was -3.44 micrograms/dl; one case was initially missed and three fell within 0.5 microgram/dl of the cutoff. The risk for missing CHT in screening is apparent. Clinical vigilance must be maintained to detect missed cases as early as possible.

Phenylketonuria: contemporary screening and diagnosis.

Screening newborns for phenylketonuria (PKU) is a mandatory practice based on measuring a raised blood phenylalanine level. Many factors influence the rate of blood phenylalanine rise so that there are many pitfalls in detecting the 1:10,000 affected infant. About one percent of all babies tested proves to be "false positives." Two-thirds of those with persistent hyperphenylalaninemia prove to have classic PKU. Non-classic PKU with less intense, persistent hyperphenylalaninemia is due to different alterations in the enzyme, phenylalanine hydroxylase. Additionally, about one percent of the confirmed positive patients is due to either a defect in the synthesis or regeneration of the cofactor, tetrahydrobiopterin; these latter forms are not amenable to treatment with the low phenylalanine diet. Screening programs have developed directives regarding the timing and conditions for obtaining the specimens for testing. Specific confirmatory tests of those with positive results must be performed. Even so, about one in 70 affected babies is "missed," resulting in mental retardation, seizures, and neurologic deficits.

A source of error in phenylketonuria screening.

The escalating number of blood specimens from late-fed premature or very sick newborns greatly increases the risk of missing the diagnosis of phenylketonuria (PKU). Babies receiving antibiotics have uninterpretable "clear-zone" results with the traditional Guthrie bacteriologic inhibition assay (BIA). For the past year the authors have reexamined the blood phenylalanine level on specimens giving the "clear-zone" effect by BIA by use of the McCaman-Robins chemical-fluorescent assay (CFA). Spuriously high blood phenylalanine levels occurred in four babies who were receiving ampicillin and whose specimens were collected on filter paper and autoclaved in preparation for the BIA. None of the babies proved to have PKU. The fluorescent interference caused by ampicillin resulted from the heat of autoclaving the specimen. The authors recommend that the blood specimen should not be autoclaved before analysis by either BIA or CFA.

The association of significant renal anomalies with Turner's syndrome.

The incidence of significant renal anomalies in 38 patients with Turner's syndrome was 26 per cent (10 of 38 cases). An additional 11 per cent of the patients have insignificant renal abnormalities and 63 per cent apparently have normal excretory urograms. In this series there seemed to be no correlation of the incidence of abnormalities with either the phenotypic or karyotypic expression of Turner's syndrome, that is the 45/XO pattern of the mosaic variants. Therefore, clinicians should be aware that any patient with Turner's syndrome must receive a thorough clinical and radiologic evaluation of the urogenital tract.

Congenital graves disease. Four familial cases with long-term follow-up and perspective.

Congenital Graves disease has been described as a transient disorder in which the mother has or has had hyperthyroidism. Experience with four affected children to ages 5 to 9 years and a review of published cases led us to conclude that long-acting thyroid stimulator (half-life, six days) is not the cause of the disease. This disease occurs in infants from families with a high incidence of Graves disease, and, in many, hyperthyroidism persists for months or years. The pathogenesis of Graves disease is unknown, and the simplistic maternal-to-fetal humoral theory is not a suitable explanation for congenital Graves disease. If Graves disease is considered in the larger perspective than the maternal-fetal unit, a pattern of inheritance is apparent, ie, an autosomal-dominant trait with a predilection for the female individual.

Trismus pseudocamptodactyly syndrome: Dutch-Kentucky syndrome.

A hand, foot, and mouth combination of anomalies, which is apparent on motion, has been traced through eight generations of a southern Appalachian family. The clinical features from birth to old age are presented, and attention is called to the handicapping aspects. There is a great variability in severity of the trait. Inheritance occurs as an autosomal dominant trait, but there are fewer affected persons than expected, especially females.