Bladder Diverticula and Menkes'
Syndrome 1
Pediatric Radiology
H. Theodore Harcke, Jr. M.D., Marie A. Capitanio, M.D., Warren D. Grover, M.D., and Marie Valdes-Dapena, M.D.2 Multiple unusual diverticula of the bladder were observed in 3 of 4 children with Menkes' syndrome. This abnormality of the bladder in children with the kinky hair syndrome has only recently been recognized. The diverticula are best visualized on cystographic studies. The clinical manifestation which led to roentgen evaluation of the urinary tract in the 3 children was urinary tract infection or urine retention. Though the etiology of these diverticula is unknown, evidence is presented to suggest that they are acquired. INDEX TERMS: Bladder • (Bladder, diverticula, 8 [3] .1491) • Familial conditions • (Skeletal system, Menkes' kinky hair syndrome, 4[8].1726) Radiology 124:459-461, August 1977
CLINICAL AND ROENTGENOGRAPHIC FINDINGS
Examination of hair from the scalp revealed pili torti and monilethrix. His serum copper level was 19 mg/dl (normal range for age is 75-90 mg/dl). Roentgen examination of his skeleton revealed worm ian bones in the lambdoid suture of the skull; otherwise the skeleton was normal. A cerebral angiogram performed at one month of age was normal. The child had been treated with infusions of copper ever since the diagnosis of Menke's syndrome was confirmed. When the child was one year of age a positive urine culture obtained during a febrile episode prompted roentgenographic examination of the urinary tract. Cystourethrography revealed several diverticula at the base of the bladder. The bladder was of normal size, the urethra was normal, there was no vesicoureteral reflux, and spontaneous voiding resulted in satisfactory emptying of the bladder (Fig. 1). The excretory urogram was normal. The child is now 3 %years of age and has had recurrent urinary tract infections. A recent physical examination revealed bladder distention and diminished urinary stream during voiding.
CASE I: J. D. was admitted to St. Christopher's Hospital for Children at 3 days of age. He is the cousin of a child who had been diagnosed at St. Christopher's Hospital for Children as having Menkes' syndrome. On admission his hair was noted to be kinky and he was hypotonic.
CASE II: W. D. is the cousin of J. D. (CASE I) and the sibling of a child with Menkes' disease. Shortly after birth he was admitted to St. Christopher's Hospital for Children where trichopoliodystrophy was diagnosed. His hair was abnormal and his serum copper level was 30-40
of the bladder were observed in 3 of 4 children with Menkes' syndrome admitted to St. Christopher's Hospital for Children. This abnormality of the bladder in children with kinky hair syndrome or trichopoIiodystrophy has only recently been recognized (7). The diverticula are usually multiple, vary in size and location, and produce an unusual and at times bizarre roentgen appearance of the bladder. The purpose of this report is threefold: (a) to confirm the presence of bladder diverticula in Menke's syndrome previously reported in two children; (b) to present for the first time the roentgen appearance of these unusual diverticula; and (c) to document the observations in three children.
D
IVERTICULA
Fig. 1.
A and B. CASE I. Cystogram. Note diverticula posterolaterally. The urethra is normal.
1 From the Departments of Radiology (H.T.H., M.A.C.), Neurology (W.D.G.) and Pathology (M.V.D.) of St. Christopher's Hospital for Children and Temple University School of Medicine, Philadelphia, Pa. Accepted for publlcatlon in March 1977. Supported by Developmental Training Grant #5-T01-NS10072-02. 2 Present address: Department of Pathology, Jackson Memorial Hospital and University of Miami School of Medicine, Miami, Fla. emt
459
460
H. THEODORE HARCKE, JR. AND OTHERS
August 1977
Fig. 2. CASE II. A. Cystography reveals multiple bladder diverticula and bilateral ureteral reflux. B. Note distortion of the base of the bladder and the normal urethra during the Crede maneuver. mg/dl (normal, 75-90 mg/dl). Numerous wormian bones were noted on roentgenographic examination of the skull. Radiographic studies of the skeleton revealed no other abnormalities. An excretory urogram and cystogram were performed because sepsis and positive urine cultures were documented in the neonatal period, and multiple bladder diverticula were noted in both studies. During the cystographic study bilateral ureteral reflux occurred. He did not void spontaneously; with the Crede maneuver a normal urethra was visualized (Fig. 2). Despite therapy with a copper chellate by mouth and the subcutaneous administration of copper salts for a period of three months, the child experienced a major motor seizure and expired one day later following a cardiopulmonary arrest. Postmortem studies of the urinary tract revealed slight dilatation of the renal pelves and a markedly abnormal bladder. The bladder wall was markedly hypertrophied and globular, and both ureters entered the bladder through relatively large posterolateral thin-walled sac-like structures which projected outward from the bladder (Fig. 2). Two small diverticula (5 mm in diameter) were noted in relation to the right ureter. Histologic sections stained specifically for elastic tissues were made of the aorta, pulmonary artery, mesenteric arteries, and the bladder. Fragmentation characteristic of Menkes' disease was noted in elastic fibers of the aorta, pulmonary arteries, and mesenteric arteries. The elastic tissue of the bladder wall appeared normal, but the walls of the diverticula were composed almost exclusively of elastic tissue. CASE III: T. L. was admitted to St. Christopher's Hospital for Children at 2 years of age. Menkes' syndrome had been diagnosed when he was 8 months of age. At that time the serum copper level was 32 mg/dl and ceruloplasm, 14.4 mg/dl. Copper infusion therapy was initiated and continued after his discharge from hospital. At the time of his admission to St. Christopher's Hospital for Children a skeletal survey revealed flaring of the metaphyses of the long bones, metaphyseal infractions, and periosteal new bone along the diaphyses. Flaring and cupping of the anterior ends of the ribs were also noted. At 18 months of age he had been hospitalized for urinary retention. Following that episode he continued to have dysuria and intermittent distension of the bladder. A cystogram revealed multiple diverticula which obscured the normal
anatomic landmarks of the bladder (Fig. 3). There was no ureteral reflux. The patient was unable to void. Numerous attempts to visualize the urethra by the Crade maneuver resulted only in displacment of contrast material from one diverticulum to another. The bladder could not be emptied even by catheter as contrast material remained in many of the diverticula. An excretory urogram revealed normal pelvocalyceal systems and ureters.
DISCUSSION
Menkes' syndrome (trichopoliodystrophy, kinky hair disease, steely hair disease) is a sex-linked progressive neurodegenerative disorder characterized by friable hair, psychomotor retardation and growth failure. Osseous changes resembling scurvy, as well as irregularity and tortuosity of vessels, have also been described (6). A defect in copper metabolism has been shown to be the underlying abnormality in Menkes' syndrome. Copper is an essential component of a number of enzymes including those necessary for cell function, especially nerve cells and elastic tissue (1). An abnormality in copper binding or copper utilization which results in enzyme dysfunction is probably responsible for the neurodegenerative changes and fragmentation of elastic fibers noted in various types of arteries in patients with trichopoliodystrophy. The cause of the bladder diverticula in children with Menkes disease is not known. The postmortem findings in CASE II, however, have provided us with considerable information concerning the nature of the diverticula. Bladder diverticula have been classified as congenital or acquired depending on the histology of the walls of the diverticula. The wall of the congenital diverticulum is said to contain all the components of the bladder wall including
Vol. 124
461
BLADDER DIVERTICULA AND MENKES' SYNDROME
Pediatric Radiology
Fig. 3. CASE III. A. Numerous diverticula obscure the normalanatomiclandmarks of the bladder. B. Noteappearance of bladder anddiverticula after attempts at drainage by catheter.
a transitional epithelial layer, tunica propria, muscularis, and serosa. By contrast, the wall of an acquired diverticulum is purported to consist of an epithelial lining, tunica propria, and little or no smooth muscle (5). Thus, according to this classification, the bladder diverticula in CASE II are acquired. There is little elastic tissue in the normal bladder; the few elastic fibers are located in the tunica propria (3). The elastic fibers in the tunica propria of the bladder and the diverticula of CASE II were not disrupted or fragmented as they were in several arteries, and the quantity of elastic tissue in the wall of the child's bladder appeared normal. The apparent increase in elastic tissue in the walls of the diverticula may be explained by the absence of smooth muscle and the compression of the reticular network of the tunica propria. These findings suggest that bladder diverticula are not caused by defective elastic tissue. In view of the severe progressive neurodegenerative changes which characterize Menkes' disease, bladder diverticula may be a consequence of an increasing disturbance in innervation of the bladder. The two children who had the most severe bladder deformities were unable to void spontaneously although neither had evidence of a mechanical obstruction. The bladder deformities in the children with Menkes' syndrome are not typical of the atonic or hypertonic forms of neurogenic bladders (4), but the findings in the 3 children indicate a disturbance in innervation of the bladder which may be progressive. The discovery of bladder diverticula in children with Menkes' syndrome is significant in light of recent attempts
to treat the disease with infusions of copper (2). The value of copper replacement therapy in trichopoliodystrophy remains uncertain. Roentgen examination of the urinary tract including the excretory urogram and cystogram should be included in the total evaluation of patients with Menkes' disease because diverticula constitute sites of urinary stasis which may lead to infection. ADDENDUM: Following ourobservations, Dr. Robert Lebowitz of the Children's Hospital Medical Center in Boston hasinformed usof another child with Menkes' syndrome with bladder diverticula.
H. Theodore Harcke, Jr., M.D. Department of Radiology St. Christopher's Hospital for Children 2600 North Lawrence St. Philadelphia, Pa. 19133
REFERENCES 1. Danks OM, Campbell PE, Walker-Smith J, et al: Menkes' kinky hair syndrome. Lancet 1:1100-1102, May 1972 2. Grover WD, Scrutton MC: Copper infusion therapy in trichopoliodystrophy. J Pediatr 86:216-220, Feb 1975 3. Ham AW: Histology. Philadelphia, Lippincott, 7th ed, 1974 4. Ney C, Friedenberg RM: Radiography Atlas of theGenitourinary system. Philadelphia, Lippincott, 1966 5. Robbins SL: Pathology. Philadelphia, Saunders, 1967 6. Wesenberg RL, Gwinn JL,Barnes GR Jr: Radiological findings in the kinky-hair syndrome. Radiology 92:500-506, Mar 1969 7. Wheeler EM, Roberts PF: Menkes' steely hairsyndrome. Arch Dis Child 51:269-274, Apr 1976
Syndrome 1
Pediatric Radiology
H. Theodore Harcke, Jr. M.D., Marie A. Capitanio, M.D., Warren D. Grover, M.D., and Marie Valdes-Dapena, M.D.2 Multiple unusual diverticula of the bladder were observed in 3 of 4 children with Menkes' syndrome. This abnormality of the bladder in children with the kinky hair syndrome has only recently been recognized. The diverticula are best visualized on cystographic studies. The clinical manifestation which led to roentgen evaluation of the urinary tract in the 3 children was urinary tract infection or urine retention. Though the etiology of these diverticula is unknown, evidence is presented to suggest that they are acquired. INDEX TERMS: Bladder • (Bladder, diverticula, 8 [3] .1491) • Familial conditions • (Skeletal system, Menkes' kinky hair syndrome, 4[8].1726) Radiology 124:459-461, August 1977
CLINICAL AND ROENTGENOGRAPHIC FINDINGS
Examination of hair from the scalp revealed pili torti and monilethrix. His serum copper level was 19 mg/dl (normal range for age is 75-90 mg/dl). Roentgen examination of his skeleton revealed worm ian bones in the lambdoid suture of the skull; otherwise the skeleton was normal. A cerebral angiogram performed at one month of age was normal. The child had been treated with infusions of copper ever since the diagnosis of Menke's syndrome was confirmed. When the child was one year of age a positive urine culture obtained during a febrile episode prompted roentgenographic examination of the urinary tract. Cystourethrography revealed several diverticula at the base of the bladder. The bladder was of normal size, the urethra was normal, there was no vesicoureteral reflux, and spontaneous voiding resulted in satisfactory emptying of the bladder (Fig. 1). The excretory urogram was normal. The child is now 3 %years of age and has had recurrent urinary tract infections. A recent physical examination revealed bladder distention and diminished urinary stream during voiding.
CASE I: J. D. was admitted to St. Christopher's Hospital for Children at 3 days of age. He is the cousin of a child who had been diagnosed at St. Christopher's Hospital for Children as having Menkes' syndrome. On admission his hair was noted to be kinky and he was hypotonic.
CASE II: W. D. is the cousin of J. D. (CASE I) and the sibling of a child with Menkes' disease. Shortly after birth he was admitted to St. Christopher's Hospital for Children where trichopoliodystrophy was diagnosed. His hair was abnormal and his serum copper level was 30-40
of the bladder were observed in 3 of 4 children with Menkes' syndrome admitted to St. Christopher's Hospital for Children. This abnormality of the bladder in children with kinky hair syndrome or trichopoIiodystrophy has only recently been recognized (7). The diverticula are usually multiple, vary in size and location, and produce an unusual and at times bizarre roentgen appearance of the bladder. The purpose of this report is threefold: (a) to confirm the presence of bladder diverticula in Menke's syndrome previously reported in two children; (b) to present for the first time the roentgen appearance of these unusual diverticula; and (c) to document the observations in three children.
D
IVERTICULA
Fig. 1.
A and B. CASE I. Cystogram. Note diverticula posterolaterally. The urethra is normal.
1 From the Departments of Radiology (H.T.H., M.A.C.), Neurology (W.D.G.) and Pathology (M.V.D.) of St. Christopher's Hospital for Children and Temple University School of Medicine, Philadelphia, Pa. Accepted for publlcatlon in March 1977. Supported by Developmental Training Grant #5-T01-NS10072-02. 2 Present address: Department of Pathology, Jackson Memorial Hospital and University of Miami School of Medicine, Miami, Fla. emt
459
460
H. THEODORE HARCKE, JR. AND OTHERS
August 1977
Fig. 2. CASE II. A. Cystography reveals multiple bladder diverticula and bilateral ureteral reflux. B. Note distortion of the base of the bladder and the normal urethra during the Crede maneuver. mg/dl (normal, 75-90 mg/dl). Numerous wormian bones were noted on roentgenographic examination of the skull. Radiographic studies of the skeleton revealed no other abnormalities. An excretory urogram and cystogram were performed because sepsis and positive urine cultures were documented in the neonatal period, and multiple bladder diverticula were noted in both studies. During the cystographic study bilateral ureteral reflux occurred. He did not void spontaneously; with the Crede maneuver a normal urethra was visualized (Fig. 2). Despite therapy with a copper chellate by mouth and the subcutaneous administration of copper salts for a period of three months, the child experienced a major motor seizure and expired one day later following a cardiopulmonary arrest. Postmortem studies of the urinary tract revealed slight dilatation of the renal pelves and a markedly abnormal bladder. The bladder wall was markedly hypertrophied and globular, and both ureters entered the bladder through relatively large posterolateral thin-walled sac-like structures which projected outward from the bladder (Fig. 2). Two small diverticula (5 mm in diameter) were noted in relation to the right ureter. Histologic sections stained specifically for elastic tissues were made of the aorta, pulmonary artery, mesenteric arteries, and the bladder. Fragmentation characteristic of Menkes' disease was noted in elastic fibers of the aorta, pulmonary arteries, and mesenteric arteries. The elastic tissue of the bladder wall appeared normal, but the walls of the diverticula were composed almost exclusively of elastic tissue. CASE III: T. L. was admitted to St. Christopher's Hospital for Children at 2 years of age. Menkes' syndrome had been diagnosed when he was 8 months of age. At that time the serum copper level was 32 mg/dl and ceruloplasm, 14.4 mg/dl. Copper infusion therapy was initiated and continued after his discharge from hospital. At the time of his admission to St. Christopher's Hospital for Children a skeletal survey revealed flaring of the metaphyses of the long bones, metaphyseal infractions, and periosteal new bone along the diaphyses. Flaring and cupping of the anterior ends of the ribs were also noted. At 18 months of age he had been hospitalized for urinary retention. Following that episode he continued to have dysuria and intermittent distension of the bladder. A cystogram revealed multiple diverticula which obscured the normal
anatomic landmarks of the bladder (Fig. 3). There was no ureteral reflux. The patient was unable to void. Numerous attempts to visualize the urethra by the Crade maneuver resulted only in displacment of contrast material from one diverticulum to another. The bladder could not be emptied even by catheter as contrast material remained in many of the diverticula. An excretory urogram revealed normal pelvocalyceal systems and ureters.
DISCUSSION
Menkes' syndrome (trichopoliodystrophy, kinky hair disease, steely hair disease) is a sex-linked progressive neurodegenerative disorder characterized by friable hair, psychomotor retardation and growth failure. Osseous changes resembling scurvy, as well as irregularity and tortuosity of vessels, have also been described (6). A defect in copper metabolism has been shown to be the underlying abnormality in Menkes' syndrome. Copper is an essential component of a number of enzymes including those necessary for cell function, especially nerve cells and elastic tissue (1). An abnormality in copper binding or copper utilization which results in enzyme dysfunction is probably responsible for the neurodegenerative changes and fragmentation of elastic fibers noted in various types of arteries in patients with trichopoliodystrophy. The cause of the bladder diverticula in children with Menkes disease is not known. The postmortem findings in CASE II, however, have provided us with considerable information concerning the nature of the diverticula. Bladder diverticula have been classified as congenital or acquired depending on the histology of the walls of the diverticula. The wall of the congenital diverticulum is said to contain all the components of the bladder wall including
Vol. 124
461
BLADDER DIVERTICULA AND MENKES' SYNDROME
Pediatric Radiology
Fig. 3. CASE III. A. Numerous diverticula obscure the normalanatomiclandmarks of the bladder. B. Noteappearance of bladder anddiverticula after attempts at drainage by catheter.
a transitional epithelial layer, tunica propria, muscularis, and serosa. By contrast, the wall of an acquired diverticulum is purported to consist of an epithelial lining, tunica propria, and little or no smooth muscle (5). Thus, according to this classification, the bladder diverticula in CASE II are acquired. There is little elastic tissue in the normal bladder; the few elastic fibers are located in the tunica propria (3). The elastic fibers in the tunica propria of the bladder and the diverticula of CASE II were not disrupted or fragmented as they were in several arteries, and the quantity of elastic tissue in the wall of the child's bladder appeared normal. The apparent increase in elastic tissue in the walls of the diverticula may be explained by the absence of smooth muscle and the compression of the reticular network of the tunica propria. These findings suggest that bladder diverticula are not caused by defective elastic tissue. In view of the severe progressive neurodegenerative changes which characterize Menkes' disease, bladder diverticula may be a consequence of an increasing disturbance in innervation of the bladder. The two children who had the most severe bladder deformities were unable to void spontaneously although neither had evidence of a mechanical obstruction. The bladder deformities in the children with Menkes' syndrome are not typical of the atonic or hypertonic forms of neurogenic bladders (4), but the findings in the 3 children indicate a disturbance in innervation of the bladder which may be progressive. The discovery of bladder diverticula in children with Menkes' syndrome is significant in light of recent attempts
to treat the disease with infusions of copper (2). The value of copper replacement therapy in trichopoliodystrophy remains uncertain. Roentgen examination of the urinary tract including the excretory urogram and cystogram should be included in the total evaluation of patients with Menkes' disease because diverticula constitute sites of urinary stasis which may lead to infection. ADDENDUM: Following ourobservations, Dr. Robert Lebowitz of the Children's Hospital Medical Center in Boston hasinformed usof another child with Menkes' syndrome with bladder diverticula.
H. Theodore Harcke, Jr., M.D. Department of Radiology St. Christopher's Hospital for Children 2600 North Lawrence St. Philadelphia, Pa. 19133
REFERENCES 1. Danks OM, Campbell PE, Walker-Smith J, et al: Menkes' kinky hair syndrome. Lancet 1:1100-1102, May 1972 2. Grover WD, Scrutton MC: Copper infusion therapy in trichopoliodystrophy. J Pediatr 86:216-220, Feb 1975 3. Ham AW: Histology. Philadelphia, Lippincott, 7th ed, 1974 4. Ney C, Friedenberg RM: Radiography Atlas of theGenitourinary system. Philadelphia, Lippincott, 1966 5. Robbins SL: Pathology. Philadelphia, Saunders, 1967 6. Wesenberg RL, Gwinn JL,Barnes GR Jr: Radiological findings in the kinky-hair syndrome. Radiology 92:500-506, Mar 1969 7. Wheeler EM, Roberts PF: Menkes' steely hairsyndrome. Arch Dis Child 51:269-274, Apr 1976
