Isolated hyperchlorhidrosis is an autosomal recessive condition in which excessive salt wasting in sweat can result in severe infantile hyponatremic dehydration and hyperkalemia (summary by Muhammad et al., 2011).
Feldshtein et al. (2010) reported a large multigenerational Israeli Bedouin kindred in which 7 individuals had isolated hyperchlorhidrosis. Two patients presented in infancy with hyponatremic dehydration associated with gastroenteritis. Sodium supplementation was effective treatment. Testing of sweat showed ... Feldshtein et al. (2010) reported a large multigenerational Israeli Bedouin kindred in which 7 individuals had isolated hyperchlorhidrosis. Two patients presented in infancy with hyponatremic dehydration associated with gastroenteritis. Sodium supplementation was effective treatment. Testing of sweat showed increased chloride levels, but cystic fibrosis (CF; 219700) was excluded. Screening of the extended family identified 5 additional individuals with hyperchlorhidrosis, 3 of whom had episodes of hyponatremic dehydration during infancy. All patients reported dramatically increased amounts of visible salt precipitates in sweat, particularly at the nape. By 1 year of age, all had achieved normal growth parameters and none had developmental abnormalities. All affected individuals were too young to allow investigation of infertility, and none had pulmonary abnormalities. Serum and urinary electrolytes, as well as renal function, were normal. Muhammad et al. (2011) reported 3 consanguineous Bedouin families from the same extended clan with infantile-onset of hyponatremic dehydration. All showed failure to thrive, and 2 had symptoms of gastroenteritis. Laboratory studies showed hyponatremia, hyperkalemia, increased aldosterone, and increased sweat chloride concentrations. Oral sodium chloride administration resulted in clinical improvement. Two patients showed catch-up growth, but had salt cravings at ages 6 and 5.5 years, respectively. The third patient had other episodes, due to poor compliance, but later showed catch-up growth. All had normal blood pressure and renal function during follow-up. Two asymptomatic adult homozygous mutation carriers were identified in the family; only 1 of them had increased sweat chloride levels. Muhammad et al. (2011) noted the phenotypic similarity of the disorder to autosomal recessive pseudohypoaldosteronism type I (PHA1B; 264350).
By sequencing of candidate genes within a region of homozygosity on chromosome 15q22, Feldshtein et al. (2010) identified a homozygous mutation in the CA12 gene (E143K; 603263.0001) in affected members of an Israeli Bedouin family with isolated hyperchlorhidrosis. ... By sequencing of candidate genes within a region of homozygosity on chromosome 15q22, Feldshtein et al. (2010) identified a homozygous mutation in the CA12 gene (E143K; 603263.0001) in affected members of an Israeli Bedouin family with isolated hyperchlorhidrosis. The mutation mildly reduced carbonic anhydrase activity, but caused a dramatic change in chloride-mediated negative feedback regulation of the enzyme, leading to excessive chloride secretion in sweat. By genomewide linkage analysis followed by candidate gene sequencing in 3 consanguineous Bedouin families with salt wasting in sweat, Muhammad et al. (2011) identified the homozygous E143K mutation in the CA12 gene.