Summary One proven and one probable case of CEP in second cousins from Northern Norway are reported. The porphyrin pattern in Case 1, who has been studied extensively, in certain respects differs from that reported earlier in CEP, indicating that the disease may be genetically heterogeneous. The most impressive finding is the extraordinary high amounts of 7 carboxylic porphyrin in urine. Isomer analysis has shown this porphyrin to belong to the isomer III series. The presence of increased amounts of protoporphyrin in plasma and feces is also at variance with the picture seen in classical CEP.

Three children with familial hypomagnesemia from infancy were treated perorally with magnesium for 9 to 12 years. Their somatic and intellectual development have since been normal. Without therapy, the serum magnesium fell from subnormal (about 0.5 mmoles/liter) to very low values (0.2 to 0.3 mmoles/liter) within 1 to 4 wk. We observed a secondary fall in serum calcium and potassium and an increase in sodium and phosphate although serum concentrations of PTH, calcitonin, and 25-OH-vitamin D in the blood remained normal. Balance studies confirmed the presence of a defect in the intestinal absorption of magnesium and excluded a defective renal tubular transport system. The subjects continued to require daily magnesium supplements to avoid serious symptoms. Optimal dosage was found to be in the range 0.5 to 0.75 mmoles/kg*day; doses above this caused diarrhoea and a fall in the serum and urine levels of magnesium. Pathophysiologic mechanisms involved in the electrolyte changes that occurred secondarily to the hypomagnesemia are discussed. SpeculationThe pathophysiologic basis for the impaired intestinal absorp tion of magnesium in this condition is unknown. In fact, the mechanism by which magnesium is normally transported across membranes is also largely unknown. A facilitated transport mechanism seems to be involved. It appears reasonable to believe that errors in enzymes. or perhaps more likely, in specific magnesiumbinding proteins that are involved in the membrane transport form the molecular basis for familial hypomagnesemia.Familial hypomagnesemia was first described in 1965 (23). Subsequently, a total of 18 cases have been reported (2,4,6,7,10,13,15,19, 23,24,26, 28, 30,31,32,34,37). In addition, five older siblings of these index cases died with a clinical picture consistent with familial hypomagnesemia, but without a verified diagnosis (Table I). The usual age of onset was 2 to 4 wk; however, two women first became symptomatic during adulthood. This type of congenital primary hypomagnesemia appears to be due to a specific defect in the intestinal absorption of magnesium (28,32).For 9 to 12 years, we have followed three children with familial hypomagnesemia diagnosed during infancy. In the absence of data from long-term follow-up studies, we have reviewed our subjects as to their growth and development and evaluated their need for extra magnesium supplementation and the degree of homeostatic lability. rGorted previously (28j. He was treated daily with oral magnesium lactate powder until 12 years of age, followed by a magnesium sulphate mixture (0.75 mmoles/kg.day). He has developed normally without convulsions. His serum magnesium has consistently been subnormal: 0.5 to 0.6 mmoles/liter.T. B., born 8/16/67, was the second child of healthy, nonconsanguineous parents. He was born at term after a normal pregnancy and delivery. Symptoms of hypomagnesemia appeared at the age of 3 wk. The course through infancy has previously been reported (32). From the fourth wk of life, he received daily supplements of magnesi...

Pediatr. Res. 15: 1 134-1 139 (198 1) calcitonin parathyroid hormone calcium potassium hypomagnesemia sodium magnesium vitamin D Summary age of 4 wk. The development during the first 18 months has been Three children with familial hypomagnesemia from infancy were treated perorally with magnesium for 9 to 12 years. Their somatic and intellectual development have since been normal. Without therapy, the serum magnesium fell from subnormal (about 0.5 mmoles/liter) to very low values (0.2 to 0.3 mmoles/liter) within 1 to 4 wk. We observed a secondary fall in serum calcium and potassium and an increase in sodium and phosphate although serum concentrations of PTH, calcitonin, and 25-OH-vitamin D in the blood remained normal. Balance studies confirmed the presence of a defect in the intestinal absorption of magnesium and excluded a defective renal tubular transport system. The subjects continued to require daily magnesium supplements to avoid serious symptoms. Optimal dosage was found to be in the range 0.5 to 0.75 mmoles/kg*day; doses above this caused diarrhoea and a fall in the serum and urine levels of magnesium. Pathophysiologic mechanisms involved in the electrolyte changes that occurred secondarily to the hypomagnesemia are discussed. Speculation The pathophysiologic basis for the impaired intestinal absorp tion of magnesium in this condition is unknown. In fact, the mechanism by which magnesium is normally transported across membranes is also largely unknown. A facilitated transport mechanism seems to be involved. It appears reasonable to believe that errors in enzymes. or perhaps more likely, in specific magnesium-binding proteins that are involved in the membrane transport form the molecular basis for familial hypomagnesemia. Familial hypomagnesemia was first described in 1965 (23). Subsequently, a total of 18 cases have been reported (2,4,6, 7, 10, 13, 15, 19, 23, 24, 26, 28, 30, 31, 32, 34, 37). In addition, five older siblings of these index cases died with a clinical picture consistent with familial hypomagnesemia, but without a verified diagnosis (Table I). The usual age of onset was 2 to 4 wk; however, two women first became symptomatic during adulthood. This type of congenital primary hypomagnesemia appears to be due to a specific defect in the intestinal absorption of magnesium (28, 32). For 9 to 12 years, we have followed three children with familial hypomagnesemia diagnosed during infancy. In the absence of data from long-term follow-up studies, we have reviewed our subjects as to their growth and development and evaluated their need for extra magnesium supplementation and the degree of homeostatic lability. rGorted previously (28j. He was treated daily with oral magnesium lactate powder until 12 years of age, followed by a magnesium sulphate mixture (0.75 mmoles/kg.day). He has developed normally without convulsions. His serum magnesium has consistently been subnormal: 0.5 to 0.6 mmoles/liter. T. B., born 8/16/67, was the second child of healthy, noncon-sanguineous parents. He was born at term after...

Summary The effect of various types of measures taken for light shielding against daylight in a recently detected case of CEP, has been followed for more than a year. It has been found that the celluloid film, “Para‐Sol”, which has a good translucency for wavelengths above 550 nm, but is not translucent to wavelengths below 510 nm, not only removes the troublesome skin lesions seen in this disease, but also. brings about an almost complete compensation of the anemia, disappearance of the splenomegaly and marked changes in the blood and urinary porphyrin patterns. In blood the erythrocyte porphyrins change from predominantly proto‐porphyrin with trace amounts of copro‐ and not detectable uroporphyrin, to high amounts of both proto‐, copro‐ and uroporphyrins. The plasma porphyrins remain essentially unchanged. The urinary pattern changes from predominantly free porphyrins to predominantly porphyrinogens. It is suggested that the present case of congenital erythropoietic porphyria represents a new type of CEP, and that the hemolytic anemia with splenomegaly seen in CEP is due not to the inborn error itself, but to its tissue location and photochemical effect of light of wavelengths below 510 nm, when the porphyrin/porphyrinogen‐rich erythrocytes are exposed to daylight in the skin, while the skin lesions have been shown to depend primarily on the presence of an increase in the amounts of porphyrin/porphyrinogen in plasma. Cattle and the species Sciurus niger are mentioned as examples of species in which the light‐shielding effect of the fur has allowed the CEP‐gene to spread.