410
3. 4.
Brief clinical and laboratory observations
Kagan IG: Current status of serologic testing for parasitic diseases, Hosp Practice 9:157, 1974. Markert CL, and Moller F: Multiple forms o f enzymes: tissue, ontogenetic, and species specific patterns, Proc Nat Acad Sci 45:753, 1959.
Galactokinase deficiency presenting as pseudotumor cerebri Nathan Litman, M.D., Alan I. Kanter, M.D., and Laurence Finberg, M.D., Bronx, N. Y.
D I S T U R B A N C E S in galactose m e t a b o l i s m f r o m defic i e n c y o f t h e e n z y m e galactose uridyl t r a n s f e r a s e m a y c a u s e cataracts a n d liver a n d b r a i n damage. T h e m o r e recently discovered deficiency of galactokinase has b e e n t h o u g h t to b e a b e n i g n c o n d i t i o n o t h e r t h a n c a u s ing cataracts. A 2 - m o n t h - o l d f e m a l e i n f a n t p r e s e n t e d w i t h a p i c t u r e o f p s e u d o t u m o r cerebri, cataracts, a n d a u r i n a r y r e d u c i n g s u b s t a n c e . S h e was f o u n d to be defic i e n t in g a l a c t o k i n a s e a n d was fed a lactose-free form u l a w i t h i m p r o v e m e n t in t h e physical a b n o r m a l i t i e s . It a p p e a r s t h a t g a l a c t o k i n a s e - d e f i c i e n t g a l a c t o s e m i a m a y n o t b e as b e n i g n as p r e v i o u s l y s u p p o s e d . CASE REPORT Patient V. E. was admitted at 7 weeks of age for evaluation of cataracts, rapidly enlarging head circumference, and a reducing substance in the urine.* This female infant was delivered from a gravida 3, aborta 1, para 2 A1 P2 woman during the thirtY-seventh week of gestation and weighed 2.4 kg. Head circumference measured 31.2 cm. The infant was fed a standard milk formula. There was no report of jaundice, vomiting, seizures, or liver enlargement during the neonatal period. At 4 weeks of age the infant weighed 2.6 kg and the head circumference measured 34.9 cm. Re-examination 2 weeks later demonstrated a further increase in head circumference to 37.5 cm. After admission to a local hospital, a subdural tap produced no fluid and an attempted ventricular tap was unsuccessful. Cataracts were noted for the first time and urinalysis revealed 4+ reducing substance which was not glucose. The infant was transferred to the Montefiore Hospital and
From The Department of Pediatrics, Montefiore Hospital and Medieal Center of the Albert Einstein College (~f Medicine. *The patient was referred to Montefiore Hospital and Medical Center by Dr. Hans Kunz who gave permission to publish our findings.
The Journal of Pediatrics March 1975
Zee DS, and Zinkham WH: Malate dehydrogenase in Ascaris suum: characterization, ontogeny, and genetic control, Arch Biochem Biophys 126:574, 1968.
Medical Center. She weighed 3.4 kg, her length was 54 cm, and her head circumference was 38 cm. Physical findings included very prominent scalp veins, a full anterior fontanelle, 5.5 by 3.5 cm; a posterior fontanelle, 1.5 by 1.5 cm; and sagittal suture, 0.75 cm in diameter. No bruits were heard, nor did the skull transilluminate. Bilateral lenticular cataracts were noted. The remainder of the physical and neurologic examination appeared within normal limits. The urine contained reducing substance, but was negative by glucose oxidase test. Feedings were changed to a nonlactose preparation (Pregestimil), and the urine became free of reducing substance within 12 hours. There was no family history of cataracts, seizure disorders, prolonged neonatal jaundice, mental retardation, or known galactosemia. Her parents are not related, and there are no Gypsy ancestors. A 3-year-old female sibling is healthy. Additional laboratory data included a hematocrit value of 28%, reticulocytes 4.9%, white blood cell count of 8500/mm 3, platelet count of 494,000/mm 3. Chemical determinations in serum included: calcium of 9.6 mg/dl; total protein of 5.0 gin/ dl, albumin 4.0, globulin 1.0; serum glutamic pyruvic transaminase 42 KU; total serum concentration of bilirubin 0.3 mg/dl; alkaline phosphatase 3.7 BL units. No abnormal concentration of tyrosine in the urine was found. No intracranial calcifications or abnormality of the sella turcica were noted in a roentgenogram of the skull. The parents' and sibling's levels of galactose kinase in blood are in the heterozygous range (Table I). Since discharge, the infant has been fed a lactose-free diet. There has been slight regression of her cataracts. Follow-up measurements of her head circumference have demonstrated a normal rate of growth and her sagittal suture has closed. DISCUSSION V o n R e u s s 2 in 1908 was t h e first to associate t h e ing e s t i o n o f milk w i t h t h e d e v e l o p m e n t o f liver disease, faiiure to thrive, a n d galactosemia. T w e n t y - f i v e years later, F a n c o n i 3 d e s c r i b e d a p a t i e n t w i t h c a t a r a c t s a n d a c o n d i t i o n h e t e r m e d g a l a c t o s e d i a b e t e s . I n 1956, Isselbacher and co-workers 4 reported galactose-1p h o s p h a t e uridyl t r a n s f e r a s e to b e a b s e n t in m o s t patients with galactosemia. Eleven years later Gitzelm a n n s in s e a r c h i n g for a galactose k i n a s e d e f i c i e n c y s t a t e in h u m a n b e i n g s d i s c o v e r e d t h a t F a n c o n i ' s original p a t i e n t h a d s u c h a c o n d i t i o n , n o t t h e e x p e c t e d t r a n s f e r a s e deficiency. F u r t h e r e l u c i d a t i o n o f t h e clinical a b n o r m a l i t i e s of galactose m e t a b o l i s m was m a d e
Volume 86 Number 3
Brief clinical and laboratory observations
411
Table I
Urine galactose* (mg/dl)
Serum galactose (mg/dl)
Galactose kinase activity (t~moles galactose phosphate/ ml lysed RBCs/hr)
Galactose phosphate (mgldl)
Ufidyl transferase (present or absent)
3. 4.
Brief clinical and laboratory observations
Kagan IG: Current status of serologic testing for parasitic diseases, Hosp Practice 9:157, 1974. Markert CL, and Moller F: Multiple forms o f enzymes: tissue, ontogenetic, and species specific patterns, Proc Nat Acad Sci 45:753, 1959.
Galactokinase deficiency presenting as pseudotumor cerebri Nathan Litman, M.D., Alan I. Kanter, M.D., and Laurence Finberg, M.D., Bronx, N. Y.
D I S T U R B A N C E S in galactose m e t a b o l i s m f r o m defic i e n c y o f t h e e n z y m e galactose uridyl t r a n s f e r a s e m a y c a u s e cataracts a n d liver a n d b r a i n damage. T h e m o r e recently discovered deficiency of galactokinase has b e e n t h o u g h t to b e a b e n i g n c o n d i t i o n o t h e r t h a n c a u s ing cataracts. A 2 - m o n t h - o l d f e m a l e i n f a n t p r e s e n t e d w i t h a p i c t u r e o f p s e u d o t u m o r cerebri, cataracts, a n d a u r i n a r y r e d u c i n g s u b s t a n c e . S h e was f o u n d to be defic i e n t in g a l a c t o k i n a s e a n d was fed a lactose-free form u l a w i t h i m p r o v e m e n t in t h e physical a b n o r m a l i t i e s . It a p p e a r s t h a t g a l a c t o k i n a s e - d e f i c i e n t g a l a c t o s e m i a m a y n o t b e as b e n i g n as p r e v i o u s l y s u p p o s e d . CASE REPORT Patient V. E. was admitted at 7 weeks of age for evaluation of cataracts, rapidly enlarging head circumference, and a reducing substance in the urine.* This female infant was delivered from a gravida 3, aborta 1, para 2 A1 P2 woman during the thirtY-seventh week of gestation and weighed 2.4 kg. Head circumference measured 31.2 cm. The infant was fed a standard milk formula. There was no report of jaundice, vomiting, seizures, or liver enlargement during the neonatal period. At 4 weeks of age the infant weighed 2.6 kg and the head circumference measured 34.9 cm. Re-examination 2 weeks later demonstrated a further increase in head circumference to 37.5 cm. After admission to a local hospital, a subdural tap produced no fluid and an attempted ventricular tap was unsuccessful. Cataracts were noted for the first time and urinalysis revealed 4+ reducing substance which was not glucose. The infant was transferred to the Montefiore Hospital and
From The Department of Pediatrics, Montefiore Hospital and Medieal Center of the Albert Einstein College (~f Medicine. *The patient was referred to Montefiore Hospital and Medical Center by Dr. Hans Kunz who gave permission to publish our findings.
The Journal of Pediatrics March 1975
Zee DS, and Zinkham WH: Malate dehydrogenase in Ascaris suum: characterization, ontogeny, and genetic control, Arch Biochem Biophys 126:574, 1968.
Medical Center. She weighed 3.4 kg, her length was 54 cm, and her head circumference was 38 cm. Physical findings included very prominent scalp veins, a full anterior fontanelle, 5.5 by 3.5 cm; a posterior fontanelle, 1.5 by 1.5 cm; and sagittal suture, 0.75 cm in diameter. No bruits were heard, nor did the skull transilluminate. Bilateral lenticular cataracts were noted. The remainder of the physical and neurologic examination appeared within normal limits. The urine contained reducing substance, but was negative by glucose oxidase test. Feedings were changed to a nonlactose preparation (Pregestimil), and the urine became free of reducing substance within 12 hours. There was no family history of cataracts, seizure disorders, prolonged neonatal jaundice, mental retardation, or known galactosemia. Her parents are not related, and there are no Gypsy ancestors. A 3-year-old female sibling is healthy. Additional laboratory data included a hematocrit value of 28%, reticulocytes 4.9%, white blood cell count of 8500/mm 3, platelet count of 494,000/mm 3. Chemical determinations in serum included: calcium of 9.6 mg/dl; total protein of 5.0 gin/ dl, albumin 4.0, globulin 1.0; serum glutamic pyruvic transaminase 42 KU; total serum concentration of bilirubin 0.3 mg/dl; alkaline phosphatase 3.7 BL units. No abnormal concentration of tyrosine in the urine was found. No intracranial calcifications or abnormality of the sella turcica were noted in a roentgenogram of the skull. The parents' and sibling's levels of galactose kinase in blood are in the heterozygous range (Table I). Since discharge, the infant has been fed a lactose-free diet. There has been slight regression of her cataracts. Follow-up measurements of her head circumference have demonstrated a normal rate of growth and her sagittal suture has closed. DISCUSSION V o n R e u s s 2 in 1908 was t h e first to associate t h e ing e s t i o n o f milk w i t h t h e d e v e l o p m e n t o f liver disease, faiiure to thrive, a n d galactosemia. T w e n t y - f i v e years later, F a n c o n i 3 d e s c r i b e d a p a t i e n t w i t h c a t a r a c t s a n d a c o n d i t i o n h e t e r m e d g a l a c t o s e d i a b e t e s . I n 1956, Isselbacher and co-workers 4 reported galactose-1p h o s p h a t e uridyl t r a n s f e r a s e to b e a b s e n t in m o s t patients with galactosemia. Eleven years later Gitzelm a n n s in s e a r c h i n g for a galactose k i n a s e d e f i c i e n c y s t a t e in h u m a n b e i n g s d i s c o v e r e d t h a t F a n c o n i ' s original p a t i e n t h a d s u c h a c o n d i t i o n , n o t t h e e x p e c t e d t r a n s f e r a s e deficiency. F u r t h e r e l u c i d a t i o n o f t h e clinical a b n o r m a l i t i e s of galactose m e t a b o l i s m was m a d e
Volume 86 Number 3
Brief clinical and laboratory observations
411
Table I
Urine galactose* (mg/dl)
Serum galactose (mg/dl)
Galactose kinase activity (t~moles galactose phosphate/ ml lysed RBCs/hr)
Galactose phosphate (mgldl)
Ufidyl transferase (present or absent)
