Limits...
Hypercalciuria and nephrocalcinosis as early feature of Wilson disease onset: description of a pediatric case and literature review.

Di Stefano V, Lionetti E, Rotolo N, La Rosa M, Leonardi S - Hepat Mon (2012)

Bottom Line: The symptoms began at the age of five years old, but he was not diagnosed with WD until he reached an adolescent age.We started therapy with D-Penicillamine, B-vitamin complex and recommended a low copper diet.Our case was different and peculiar from the previously described cases because the patient presented a very long history (10 years) of permanent hypercalciuria without any acute episode of nephrolithiasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Catania, Catania, Italy.

ABSTRACT

Background: Wilson's disease (WD) is a rare autosomal-recessive disorder characterized by a mutation in the ATP7B gene, located on chromosome 13, which encodes a protein involved in the metabolism of copper.

Case presentation: We described the case of an Indian male with a history of polydipsia and polyuria, related to hypercalciuria and consequent nephrocalcinosis. The symptoms began at the age of five years old, but he was not diagnosed with WD until he reached an adolescent age. We started therapy with D-Penicillamine, B-vitamin complex and recommended a low copper diet. Renal involvement in Wilson's disease, characterizing by hypercalciuria, was firstly reported by Litin in 1959.

Conclusion: Our case was different and peculiar from the previously described cases because the patient presented a very long history (10 years) of permanent hypercalciuria without any acute episode of nephrolithiasis.

No MeSH data available.


Related in: MedlinePlus

Kidney Ultrasonography Showing the Presence of Bilateral Nephrocalcinosis
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3475018&req=5

fig46: Kidney Ultrasonography Showing the Presence of Bilateral Nephrocalcinosis

Mentions: A 16 years old boy came to our attention because of polyuria (about eight liters of urine) and polydipsia associated with asthenia. There was family history of diabetes mellitus for the father and allergy to inhalants from the mother. He was second-born by normal delivery of consanguineous parents (first degree cousins); weight at birth was 3015 gr. From the age of five, the symptoms of polydipsia and polyuria have increased. At 10 years old, he suffered from a fracture of his left foot after a trauma of mild intensity. A physical examination revealed evidence of growth cessation. The patient’s weight and height were below the third percentile of growth (35, 4 Kg; 143 cm) and delayed puberty was diagnosed (absent pubarche, testicular volume 6-8 cc, penis stage was the third). At the time of admission, the patient’s clinical condition was poor, skin turgor was reduced, muscles appeared norm tonic but slightly hypertrophic. Thoracic, cardiac and abdominal examinations were normal. There was no clinical sign of neurologic diseases. Speech ability and school performance were good. Laboratory findings at admission were normal; the only abnormal values were hypophosphatemia, hypokalemia and hyper transaminasemia: (Aspartate Aminotransferase (AST) 47 U/L and Alanine Aminotransferase (ALT) 81 U/L while the normal ranges are 5-42). The diagnostic work-up for growth cessation and delayed puberty were initiated, but all of the findings were normal: thyroid hormones, gonadotropins, and IGF-1 and anti-transglutaminase antibodies. Hand and wrist x-rays confirmed the development of ossification centers in relation to chronological age (the corresponding skeletal age was 13 years old). Because of the presence of polyuria, urine specimens were examined for spot and a 24-hour sample confirmed intense polyuria (6000 ml), high urinary calcium level (670 mg; v.n. 100-300) , with normal excretion of other electrolytes, and low urinary creatinine (660 mg/24 h; v.n. 800-2000). Creatinine clearance was reduced: 70 ml/min (v.n. >100 ml/min). We tested the plasma and urinary osmolarity which were normal; the ultrasonography of abdomen showed hyper echogenic liver and pyramidal calcification of kidneys with enhanced corticomidollary differentiation features suggestive of medullary nephrocalcinosis (Figure 1), and gallbladder lithiasis. Brain and pituitary gland magnetic resonance imaging did not reveal abnormality, neither in brain parenchyma nor Sella and parasellar regions. We checked calcitonin, parathyroid hormone, renin angiotensin aldosterone system and all results were found normal. Plasmatic, urinary amino acid levels and urinary acid organics did not reveal an abnormal pattern. In order to assess a possible cause for hyper transaminasemia lipid subset, alpha 1 antitrypsin, and liver kidney microsome tests were done. The complete infectivological panel did not reveal any abnormalities. The blood gas analysis showed a normal pH and bicarbonate level. The characteristics were compatible with an incomplete distal renal tubular acidosis that is the sign of WD. Finally the levels of serum concentration of copper and ceruloplasmin were 21 mcg/dl, v.n. 70-140 and 4 mg/dl v.n. 22-58 respectively which is another possible suggestion of WD. This suspicion was confirmed by elevated copper urinary excretion (111.30 mcg/24 hours’ urine; v.n. 0-50). Liver biopsy showed typical signs of WD when viewed on an electron microscope: mild lymphocytic infiltrate and eosinophilia granulocyte, no piecemeal necrosis, fatty liver degeneration (steatosis) to medium and small lipid droplets with moderate diffuse nuclear glycogenation, numerous Mallory bodies and lobular activity. Copper’s content was 270 μg/g dry weight of liver. Slit-lamp eye examination did not reveal the presence of typical Kayser-Fleischer ring, while a bone density scan revealed significant bone demineralization (Figure 2). Molecular tests confirmed, through direct DNA sequencing, the presence of a mutation in homozygosis N1270S (belong to exon 18). We started therapy with D-Penicillamine (20 mg/Kg/day) given in three doses, one hour prior meals, B-vitamin complex and a low copper diet. Moreover, we initiated therapy for osteoporosis with Alendronate (70 mg/weekly) and calcium and D vitamin complex. After two months a decrease in urinary copper and calcium excretion were revealed. The ultrasonography features of mild hepatitis responded to treatment and hypercalciuria was slightly decreased while nephrocalcinosis was unchanged.


Hypercalciuria and nephrocalcinosis as early feature of Wilson disease onset: description of a pediatric case and literature review.

Di Stefano V, Lionetti E, Rotolo N, La Rosa M, Leonardi S - Hepat Mon (2012)

Kidney Ultrasonography Showing the Presence of Bilateral Nephrocalcinosis
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475018&req=5

fig46: Kidney Ultrasonography Showing the Presence of Bilateral Nephrocalcinosis
Mentions: A 16 years old boy came to our attention because of polyuria (about eight liters of urine) and polydipsia associated with asthenia. There was family history of diabetes mellitus for the father and allergy to inhalants from the mother. He was second-born by normal delivery of consanguineous parents (first degree cousins); weight at birth was 3015 gr. From the age of five, the symptoms of polydipsia and polyuria have increased. At 10 years old, he suffered from a fracture of his left foot after a trauma of mild intensity. A physical examination revealed evidence of growth cessation. The patient’s weight and height were below the third percentile of growth (35, 4 Kg; 143 cm) and delayed puberty was diagnosed (absent pubarche, testicular volume 6-8 cc, penis stage was the third). At the time of admission, the patient’s clinical condition was poor, skin turgor was reduced, muscles appeared norm tonic but slightly hypertrophic. Thoracic, cardiac and abdominal examinations were normal. There was no clinical sign of neurologic diseases. Speech ability and school performance were good. Laboratory findings at admission were normal; the only abnormal values were hypophosphatemia, hypokalemia and hyper transaminasemia: (Aspartate Aminotransferase (AST) 47 U/L and Alanine Aminotransferase (ALT) 81 U/L while the normal ranges are 5-42). The diagnostic work-up for growth cessation and delayed puberty were initiated, but all of the findings were normal: thyroid hormones, gonadotropins, and IGF-1 and anti-transglutaminase antibodies. Hand and wrist x-rays confirmed the development of ossification centers in relation to chronological age (the corresponding skeletal age was 13 years old). Because of the presence of polyuria, urine specimens were examined for spot and a 24-hour sample confirmed intense polyuria (6000 ml), high urinary calcium level (670 mg; v.n. 100-300) , with normal excretion of other electrolytes, and low urinary creatinine (660 mg/24 h; v.n. 800-2000). Creatinine clearance was reduced: 70 ml/min (v.n. >100 ml/min). We tested the plasma and urinary osmolarity which were normal; the ultrasonography of abdomen showed hyper echogenic liver and pyramidal calcification of kidneys with enhanced corticomidollary differentiation features suggestive of medullary nephrocalcinosis (Figure 1), and gallbladder lithiasis. Brain and pituitary gland magnetic resonance imaging did not reveal abnormality, neither in brain parenchyma nor Sella and parasellar regions. We checked calcitonin, parathyroid hormone, renin angiotensin aldosterone system and all results were found normal. Plasmatic, urinary amino acid levels and urinary acid organics did not reveal an abnormal pattern. In order to assess a possible cause for hyper transaminasemia lipid subset, alpha 1 antitrypsin, and liver kidney microsome tests were done. The complete infectivological panel did not reveal any abnormalities. The blood gas analysis showed a normal pH and bicarbonate level. The characteristics were compatible with an incomplete distal renal tubular acidosis that is the sign of WD. Finally the levels of serum concentration of copper and ceruloplasmin were 21 mcg/dl, v.n. 70-140 and 4 mg/dl v.n. 22-58 respectively which is another possible suggestion of WD. This suspicion was confirmed by elevated copper urinary excretion (111.30 mcg/24 hours’ urine; v.n. 0-50). Liver biopsy showed typical signs of WD when viewed on an electron microscope: mild lymphocytic infiltrate and eosinophilia granulocyte, no piecemeal necrosis, fatty liver degeneration (steatosis) to medium and small lipid droplets with moderate diffuse nuclear glycogenation, numerous Mallory bodies and lobular activity. Copper’s content was 270 μg/g dry weight of liver. Slit-lamp eye examination did not reveal the presence of typical Kayser-Fleischer ring, while a bone density scan revealed significant bone demineralization (Figure 2). Molecular tests confirmed, through direct DNA sequencing, the presence of a mutation in homozygosis N1270S (belong to exon 18). We started therapy with D-Penicillamine (20 mg/Kg/day) given in three doses, one hour prior meals, B-vitamin complex and a low copper diet. Moreover, we initiated therapy for osteoporosis with Alendronate (70 mg/weekly) and calcium and D vitamin complex. After two months a decrease in urinary copper and calcium excretion were revealed. The ultrasonography features of mild hepatitis responded to treatment and hypercalciuria was slightly decreased while nephrocalcinosis was unchanged.

Bottom Line: The symptoms began at the age of five years old, but he was not diagnosed with WD until he reached an adolescent age.We started therapy with D-Penicillamine, B-vitamin complex and recommended a low copper diet.Our case was different and peculiar from the previously described cases because the patient presented a very long history (10 years) of permanent hypercalciuria without any acute episode of nephrolithiasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Catania, Catania, Italy.

ABSTRACT

Background: Wilson's disease (WD) is a rare autosomal-recessive disorder characterized by a mutation in the ATP7B gene, located on chromosome 13, which encodes a protein involved in the metabolism of copper.

Case presentation: We described the case of an Indian male with a history of polydipsia and polyuria, related to hypercalciuria and consequent nephrocalcinosis. The symptoms began at the age of five years old, but he was not diagnosed with WD until he reached an adolescent age. We started therapy with D-Penicillamine, B-vitamin complex and recommended a low copper diet. Renal involvement in Wilson's disease, characterizing by hypercalciuria, was firstly reported by Litin in 1959.

Conclusion: Our case was different and peculiar from the previously described cases because the patient presented a very long history (10 years) of permanent hypercalciuria without any acute episode of nephrolithiasis.

No MeSH data available.


Related in: MedlinePlus