Deletions of chromosome 6q are rare. We report 3 new patients with 6q deletions. Case 1 is a male with an interstitial deletion [del(6)(q13q14.2)], hypotonia, speech delays, and minor anomalies. Case 2 is a male with an interstitial deletion [del(6)(q16.2q22.32)] and malformations, including truncus arteriosus and bilateral oligodactyly. Case 3 is a male with a terminal deletion [del(6)(q25.2)] with retinal pits, hydrocephalus, atrioventricular canal, and hydronephrosis. The findings in our patients and those from 57 previously reported cases demonstrated 3 phenotypic groups associated with 6q deletions. Group A [del(6)(q11-q16)] had a high incidence of hernias, upslanting palpebral fissures, and thin lips with lower frequency of microcephaly, micrognathia, and heart malformations. Group B [del(6)(q15-q25)] was associated with increased intrauterine growth retardation, abnormal respiration, hypertelorism, and upper limb malformations. Group C [del(6)(q25-qter)] was associated with retinal abnormalities, cleft palate, and genital hypoplasia. The only universal finding among all patients with 6q deletions was mental retardation. Other findings common to all 3 groups included ear anomalies (90%), hypotonia (82%), and postnatal growth retardation (68%).

Two infant gids with median facial cleft syndrome are described. The patients were the children of the same mother but of different fathers. None of the parents had the same or similar malformations. The occurrence of this rare syndrome in half‐sisters is difficult to explain; it poses questions about etiology, usually not considered if malformation syndromes are seen in sisters who are the offspring of the same mother and father, both unaffected.

SUMMARY Twenty early‐treated children with classical phenylketonuria (PKU), five early‐treated children with variant PKU and seven untreated children with hyperphenylalinemia were compared with non‐PKU family members in terms of intellectual development, and 14 school‐age PKU children were also compared for academic achievement. For the early‐treated children with classical PKU, mean IQ (98) was within the normal range, but nine of these 20 children had IQ scores more than ISD below those of family members. There was a significant negative correlation between phenylalanine concentrations at one to four years of age and later measured intelligence in these early‐treated children, but this was probably a consequence of poor dietary control in the early years. The early‐treated children with variant PKU and those with hyperphenylalaninemia had IQ scores consistent with those of unaffected family members, but untreated children with variant PKU had scores significantly lower than their own early‐treated siblings. Achievement scores of the early‐treated PKU children were consistent with their intellectual ability: they and their non‐PKU siblings had similar standard scores for reading and spelling, but arithmetic scores were significantly lower for the PKU children. Early‐treated children whose diet had been discontinued had achievement scores in all subjects below those predicted from their IQS. RÉSUMÉ Développement intellectuel et performances scolaires chez des enfants phénylcétonuriques précocement traités 20 enfants précocément traités avec phénylcétonurie classique (PCU), cinq enfants précocément traités avec PCU variante et sept enfants non traités avec hyper‐phénylalaninémie ont été compareés avec des membres de même famille non PCU en termes de développement intellectuel et 14 enfants PCU d' âge scolaire ont étéégalement compareés pour performances scolaires. Pour les enfants précocément traités avec PCU classique, le QI moyen (98) était dans les niveaux normaux, mais neuf de ces 20 enfants avaient un QI de plus de un écart‐type au‐dessous des membres de leur famille. Il y avait une corrélation négative significative entre les concentrations de phenylalanine de un à quatre ans et l' ‘intelligence appréciée ultérieurement chez ces enfants précocément traités, mais cela était probablement la conséquence d' un contrôle diététique médiocre dans les premiers âges. Les enfants précocément traités avec PCU variante et ceux avec hyperphénylalaninémie avaient des QI comparables à ceux des membres de leur famille indemnes mais les enfants non traités avec PCU variante présentaient des résultats significativement plus bas que ceux de leurs propres fréres ou soeurs traités précocément. Les performances scolaires des enfants PCU précocément traités correspondaient à leur capacityé intellectuelle = les scores standards pour la lecture et l'orthographe dtaient identiques à ceux des frères et soeurs non PCU mais les scores d' arithmétique étaient significativement plus bas pour les enfants PCU. Les enfants précocément traité...

SummaryA supplement of the branched chain amino acids, valine, isoleucine, and leucine (VIL) was administered orally to patients with phenylketonuria, either together with unrestricted diet of natural protein or with a low phenylalanine diet. The VIL supplement brought about a significant reduction of the cerebrospinal fluidserum ratio of phenylalanine from a mean value of 0.254 without VIL to 0.204 with VIL. The reduction varied from 15-40% (mean 21%). Concentrations of glycine, lysine, methionine, threonine, tryptophan, and tyrosine were within normal limits in serum and cerebrospinal fluid of infants with phenylketonuria. No amino acid imbalance was created by the supplement and no adverse effects from VIL were observed. SpeculationThe branched chain amino acids and phenylalanine share a common transport system. High levels of phenylalanine in brain of children with phenylketonuria may be reduced by administration of a supplement of valine, isoleucine and leucine (VIL). Supplementation of the low-phenylalanine diet with VIL during the first 2 years of life may add a measure of protection to the developing brain beyond that which can be achieved by diet alone. In older children, VIL supplementation may permit liberalization of the diet without unfavorable behavioral consequences.Treatment for phenylketonuria (PKU) by means of a lowphenylalanine diet has become common practice since its first use in affected newborn infants (3). The treatment partially corrects the abnormal amino acid pattern, including the high concentration of phenylalanine and its metabolites, and allows relatively normal intellectual and physical development if the treatment is begun early enough (10). Initially it was assumed that treatment would be terminated when major phases of brain growth were completed. Evidence has accumulated which suggests that termination of treatment for the patient with classic PKU, at least during the school years, is unwise (13,15,16) and it may be prudent to continue the diet into adult years for women with PKU in order to avoid the teratogenic effects of phenylalanine (6).An animal model developed in this laboratory was used to demonstrate the effects of experimental hyperphenylalaninemia (PKU) (12). Methods to inhibit the deleterious effects of phenylalanine on the central nervous system were studied in the model. Administration of branched chain amino acids, valine, isoleucine, and leucine (VIL), to pregnant rats with experimentally induced PKU prevented the decrease in fetal brain weight characteristic of PKU animals (7). A striking finding was that phenylalanine levels in brain of PKU fetuses whose mothers received VIL supplement were lower than in PKU fetuses not exposed to VIL, although fetal blood phenylalanine levels were similar. Subsequent studies suggested that isoleucine was more effective than other amino acids in exerting a beneficial effect on fetal rat brain growth (1 1).Human trials followed. VIL was first used as a supplement to the low-phenylalanine diet of several older PKU children in w...