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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2003  |  Volume : 14  |  Issue : 1  |  Page : 70-74
Paralysis Episodes in Carbonic Anhydrase II Deficiency

Nephrology Section, Suleimania Children’s Hospital, Riyadh, Saudi Arabia

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Carbonic anhydrase II (CAII) deficiency is an autosomal recessive disorder manifest by osteopetrosis, renal tubular acidosis, and cerebral calcification. Other features include growth failure and mental retardation. Complications of the osteopetrosis include frequent bone fractures, cranial nerve compression, and dental mal-occlusion. A hyper­chloremic metabolic acidosis, sometimes with hypokalemia, occurs due to renal tubular acidosis that may be proximal, distal, or more commonly, the combined type. Such patients may present with global hypotonia, muscle weakness or paralysis. We report a case of CA II deficiency with recurrent attacks of acute paralysis which was misdiagnosed initially as Guillian-Barre syndrome.

Keywords: Carbonic anhydrase II deficiency, Hypokalemia, Paralysis.

How to cite this article:
Al-Ibrahim A, Al-Harbi M, Al-Musallam S. Paralysis Episodes in Carbonic Anhydrase II Deficiency. Saudi J Kidney Dis Transpl 2003;14:70-4

How to cite this URL:
Al-Ibrahim A, Al-Harbi M, Al-Musallam S. Paralysis Episodes in Carbonic Anhydrase II Deficiency. Saudi J Kidney Dis Transpl [serial online] 2003 [cited 2023 Feb 6];14:70-4. Available from: https://www.sjkdt.org/text.asp?2003/14/1/70/33091

   Introduction Top

Carbonic anhydrase (CA) isoenzyme II is a soluble isozyme that represents the major non-hemoglobin protein in the erythrocyte. It has an important physiological function in the bone, kidney and brain.

Among the eight known CA or CA-like isoenzymes, CAII has the widest tissue distribution, the highest specific activity and the most critical action in acid-base homeostasis by acceleration of combination of CO2 and H2O to form H2CO3 which then rapidly dissociates under physiologic conditions to H + and HCO3 -. [1]

Carbonic anhydrase II deficiency is an autosomal recessive inborn error of metabolism, formerly called the syndrome of osteopetrosis, renal tubular acidosis and cerebral calcification. [2] Some patients with hyperchloremic metabolic acidosis and hypo­kalemia, caused by renal tubular acidosis (RTA), might manifest with signs and symptoms such as global hypotonia, muscle weakness or paralysis. However, recurrent episodes of hypokalemic paralysis are reported to be rare. [2],[3]

We report a case of CA II isozyme deficiency who presented with recurrent episodes of acute paralysis.

   Case Presentation Top

An 11-year-old Saudi female was referred to our hospital as a case of Guillian-Barre Syndrome for administration of immuno­globulin therapy. The child was apparently well till three days before admission to the referral hospital, when she developed muscle aches and weakness of both upper and lower limbs as well as the neck, which progressed over two days to paralysis severe enough to restrict her ability to perform any active movements.

There was no history of fever, upper respiratory tract infection, gastrointestinal symptoms, skin rash, difficulty in swallowing, behavioral changes, convulsions or head injuries. She had no problem in micturation or defecation, and had no previous similar attacks.

She was a product of uneventful pregnancy, born at term with average birth weight, and from parents belonging the same tribe. She was the third sibling amongst three brothers and three sisters, their ages ranging between fourteen years and thirteen months, all of whom were healthy. There was no history of deaths amongst the siblings or abortions and no family history of similar illness, mental retardation, multiple fractures or renal disease.

She was not doing well at school (in the third grade); she spent two years in each grade, and showed delayed motor development.

Examination revealed a fully conscious, well oriented apathetic, dysmorphic child, with a prominent narrow nose, thin upper lip, poorly developed philtrum and everted lower lip. The vital signs were normal, blood pressure was 110/70 mm Hg, she was afebrile, with respiratory and heart rates of 24/minute, and 94/minute respectively. Her body weight was 15 kg and height, 120 centimeters, which was - 3.5 SD below the mean for her age.

The muscle bulk was normal with no tenderness over the muscles. The muscle tone was normal, power was grade 3/5 and deep tendon reflexes were decreased. Sensation was normal, and there was no cranial nerve involvement. Red reflux in the right eye was absent and there was early cataract on ophthalmologic examination. Other systemic examinations were normal.

The investigation at admission were as follows: serum potassium 2.1 mmol/L, chloride 113 mmol/L, sodium 136 mmol/L; arterial blood gases: pH 7.23, PCO 2 23.6 mmol/L, HCO3 9.8 mmol/L, base excess -15.9; and creatinine phosphokinase (CPK) 1285 IU/L, (normal value 24-195 IU/L). The levels of parathyroid hormone (PTH), urea, creatinine, phosphorus, calcium, alkaline phosphatase, magnesium as well as liver function tests were normal. Hemoglobin was 124 gm/L, platelets 268,000/cu mm and white blood cell count was 7400/cu mm, (all normal). The anion gap in the blood was 15 mmol/L (normal).

The urine pH was 6 and urine anion gap was positive. Skeletal survey showed characteristic radiographic features of osteopetrosis and osteosclerotic defects in the long bones and vertebra (bone-in-bone appearance). [1],[2] [Figure - 1] and [Figure - 2] Brain computed tomography (Brain CT) showed calcification in the basal ganglia. [3] [Figure - 3] Ultrasound of the kidneys was normal.

IQ test revealed mild mental retardation. The basal auditory evoked response (BAER) was normal.

All the family members were screened for evidence of CAII isoenzyme deficiency by doing blood gases and electrolytes for hyper­chloremic metabolic acidosis and hypokalemia as well as X-rays of long bones for osteo­petrosis. No abnormality was detected in any.

The study patient was managed with intra­venous potassium supplement in a dose of 5 mmol/kg/day followed by sodium bicarbo­nate, 3 mmol/kg/day. The serum potassium and bicarbonate levels became normal in less than twenty-four hours, and the child resumed her motor activity within forty-eight hours, with normal reflexes. The potassium and bicarbonate was shifted gradually to oral administration over the next four days. At this stage, the serum potassium was 4.4 mmol/L, chloride 107 mmol/L, pH and bicarbonate were 7.34 and 25.8 mmol/L respectively.

The patient was discharged after five days in good physical condition on potassium and bicarbonate supplements both in doses of 3 mmol/kg/day.

She has been under our supervision for the last four years. During these years, she had two attacks of hypokalemic paralysis, each lasting less than twenty-four hours. On these occasions, the serum potassium levels were 2.3 and 2.0 mmol/L respectively, the pH 7.21 and 7.19, serum bicarbonate 9.0 and 8 mmol/L and chloride 111 and 112 mmol/L respectively.

During follow-up, the IQ test result showed deterioration to moderate retardation and the brain calcification involved the gray matter as well. There was no change in bone density and blood counts and the CPK remained high. The patient stopped attending special school for social reasons.

   Discussion Top

Carbonic anhydrase deficiency type II is an autosomal recessive disorder with a deficit in chromosome number eight (8q22). The geographical distribution of this disease is striking, with more than half the known cases observed in families from the Middle East and Mediterranean regions such as North Africa, Kuwait and Saudi Arabia. [2],[4],[5],[6]

A common "Arabic" mutation may be the predominant cause of CAII deficiency in this region. [8]

CAII deficiency is basically a clinical dia­gnosis; biochemical diagnosis can be made by demonstrating a severe selective reduction of CAII in erythrocyte lysate in affected children.

Deficiency of CAII results in a syndrome of osteopetrosis, renal tubular acidosis (RTA) and cerebral calcification. Other features include growth failure and mental retardation, all of which were seen in our patient, in addition to the dysmorphic features which are seen often in Saudi children. [2],[5],[6]

There was a marked increase in serum CPK activity as well as mental retardation in this patient, both of which have been recorded in this syndrome. [2] In fact, the presence of mental retardation and relative infrequency of skeletal fractures distinguish the clinical course of the patients with the Arabic mutation from those of the American and Belgian varieties. [2],[7]

Most patients with the CAII deficient syndrome have both proximal and distal renal tubular acidosis, but there is clinical heterogeneity, some have predominantly proximal RTA while in others the distal component predominates.

The distal component of the RTA can be explained by the requirement for CA in the distal tubule to titrate the OH - in the cytosol, generated by the proton translocating H+ATP as it secretes H + . Absence of CAII to perform this function limits the ability of the distal nephron to generate a pH gradient and acidify the urine maximally.

The proximal component of RTA, which is usually mild, can be explained by the requirement for CAII to accelerate the normally slow reaction to facilitate HCO3­ transport across the basolateral membrane and to recycle H + for H + secretion. Only the catalyzed reaction can take place with a normal HCO3 - filtered load.

When the patient is acidotic, CAII deficient patients have no bicarbonaturia and their proximal component is not obvious. However, when plasma HCO3 - levels are raised towards normal, bicarbonaturia appears demonstrating the significantly impaired ability to reabsorb normal level of filtered HCO3 - . [1],[2],[8],[9],[10]

Our patient had predominantly distal type of RTA, as evident by the presence of hyper­chloremic metabolic acidosis, normal serum anion gap, positive urine anion gap and a urine pH which was always above 6.

Hypokalemia and metabolic acidosis are well known to cause apathy, global hypotonia or muscle weakness and paralysis. [2] Although recurrent episodes of muscle weakness have been reported by Whyte and others to be rare, [2],[3],[11] Yoshino et al, in 1993 reported Japanese patients from three unrelated families with CAII deficiency having recurrent episodes of muscle weakness. [12],[13] However, the degree of acute paralysis was not severe as seen in our patient.

The aim of reporting this case is to increase awareness amongst pediatricians that CAII deficiency should be considered in any patient with severe acute hypotonic paralysis. Recurrence of the ailment can also occur.

   References Top

1.Sly WS, Sato S, Zhu XL. Evaluation of carbonic anhydrase isozymes in disorders involving osteopetrosis and/or renal tubular acidosis. Clin Biochem 1991;24: 311-8.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Whyte MP. Carbonic anhydrase II defici­ency. Clin Orthop 1993;294:52-63.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Bourke E, Delaney VB, Mosawi M, Reavey P, Westore M.Renal tubular acidosis and osteopetrosis in siblings. Nephron 1981; 28:268-72.  Back to cited text no. 3    
4.El-Mouzan ME, Ahlberg A, Ozaksoy D. The syndrome of osteopetrosis, renal acidosis and cerebral calcification in two sisters. Neuropediatrics 1988;19:162-5.  Back to cited text no. 4    
5.Ohlsson A, Cumming WA, Paul A, Sly WS. Carbonic anhydrase II deficiency syn­drome: recessive osteopetrosis with renal tubular acidosis and cerebral calcification. Pediatrics 1986;77:371-81.  Back to cited text no. 5  [PUBMED]  
6.Strisciuglio P, Sartorio R, Pecoraro C, Lotito F, Sly WS. Variable clinical presen­tation of carbonic anhydrase deficiency: evidence for heterogeneity? Eur J Pediatric 1990;149:337-40.  Back to cited text no. 6    
7.Skaggs LA, et al. A splice junction mutation in interon 2 of the carbonic anhydrase II gene of osteopetrosis patients from Arabic countries. Hum Mutat 1992;1(4):288-92.  Back to cited text no. 7    
8.Ohlsson A, Stark G, Sakati N. Marble brain disease; recessive osteopetrosis, renal tubular acidosis and cerebral calcification in three Saudi Arabian families. Dev Med Child Neurol 1980;22(1):72-84.  Back to cited text no. 8    
9.Sato S, Zhu XL, Sly WS. Carbonic anhydrase Isozyme IV and II in urinary membranes from carbonic anhydrase II-deficient patients. Proc Nat Acad 1990;87(16):6073-6.  Back to cited text no. 9    
10.Nagai R, Kooh SW, Balfe JW, Fenton T, Halperin ML. Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency; Pathogenesis of impaired acidi­fication. Pediatr Nephral 1997;11(5):633-6.  Back to cited text no. 10    
11.Vainsel M, Fondu P, Cadran S, Rocmans C, Gepts W. Osteopetrosis associated with proximal and distal tubular acidosis. Acta Paediatr Scand 1972;61:429-34.  Back to cited text no. 11    
12.Aramaki S, Yoshida I, Yoshino M, Kondo M, Sato Y, Noda K. Carbonic anhydrase II deficiency in three unrelated Japanese patients. J Inherited Metab Dis 1993;16(6):982-90.  Back to cited text no. 12    
13.Soda H. Carbonic anhydrase II deficiency syndrome-- clinico-pathological, biochemical and molecular studies. Kurume Med J 1994;41(4):233-40.  Back to cited text no. 13    

Correspondence Address:
Alia Al-Ibrahim
Consultant Pediatrician and Nephrologist, Head, Section of Pediatric Nephrology, Suleimania Children’s Hospital, P.O. Box 59046, Riyadh 11525
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

PMID: 17657093

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