The Occurrence of Phenylketonuria and Galactosemia Within the Same Family

Abstract

A FAMILY IN WHICH one male sibling fathered a phenylketontrric daughter and a second maine sibling fathered two galactosenric daughters prompted a detailed investigation of the immediate family members of these two siblings. This paper describes the phenylketonuric (PKU) and g<rlactosernie carrier status of the tested family members and shows the paths of inheritance of' the genes involved. This study also reveals a very high incidence of' carrier states for these two relatively rare disorders among the siblings of the two fathers described.Case Reports Case 1. An infant girl was born on September I7, I ~8I , following an uncomplicated pregnancy and delivery to a gravida 3 mother. Birthweight was 3203 g. Two older siblings were normal. Neonatal screening tests performed on the third postnata( day showed an elevated phenylalanine level, and the infant was referred to the University Hospital. Fanjily history was unremarkable except for a paternal uncle with Down's syndrome. Physical examination of the infant was normal. The child' had been breastfed since birth, and the serum phenylalanine level at 2 weeks of age was 39.8 rng/dl. The serum tyrosine level was I.f3'l nig/dl, and the urine rnetabolites were positive for phenylketones. The standard PKU diet was iniplemented at 15 days of age, and the child continues to develop and grow well.Case 2. An infant girl was born on September I ~i, 1982, to a gravida I mother whose pregnancy and delivery were uncomplicated. Birthweight was 3437 g. The prenatal and neonatal courses were unremarkable. Neonatal screening perforrned on the third day of life revealed galactose-I -phosphate greater than I2 mg/dt. and a strongly positive Beutler test. The child was readmitted to the hospital. Physical examination was crnrenr<rrl<able except for jaundice. Family history was positive for PKU in a paternal cousin. Laboratory evaluation revealed hemoglobin of 1 ~ g/dl, total bilirubirx of 17.;3 mg/d) with a direct 4f' 0.9 mg/di. SCOT of 93 lUll, urinalysis with plus 3 reducing substance, and undetectable galactose--Po4 uridyl transferase activity. The child was begun on soybean forrxrula and phototherapy with prompt rescxlutic~n of the hyperbiiirubinemia. The child contines to develc~p well.Case 3. Case 3, born April l ~JB~, was the sister of case 2. Pregnancy and delivery were uncomplicated. Birthweight was 3240 g. Because of the history of the older sister, the infant was placed on a soybeanbased formula. At 2 weeks of age, neonatal screen results for I;alactcxsernia were negative; however, red blood cell f;alactnse-I-P(~4 uridyl transferase was 0.4 units, with norma) ~~alues between 14 and 25 units.At 5 months of age, the child had an entirely rxorrnal developmental and physical examination.Comment: Because the fathers of the three infant girls just described are brothers and because of the lack of previous reports of both PKU and galactc~sen7ia occurring in the farxxilv, extensive family testing was performed. MethodsEach tested family. member, with informed consent, was given an ora...

Phenylketonuria and cystic fibrosis in the same patient

“…The association of PKU with some genetic diseases, such as Duchenne muscular dystrophy, Charcot‐Marie‐Tooth disease, Down syndrome, cystinuria, homozygous hypolipoproteinemia, galactosemia, glycogenosis and fructose intolerance and non‐genetic diseases, such as scleroderma, bilateral iris coloboma, optic atrophy and Goldenhar syndrome, has been reported previously. 3–7 …”