Metachromatic leukodystrophy in the Navajo: fallout of the American-Indian wars of the nineteenth century.

Our aim was to determine if the high frequency of metachromatic leukodystrophy (MLD) in Navajo Indians of the Southwestern United States is the result of a "genetic bottleneck" that occurred in the mid 19th century. Navajo Nation, Indian Health Service, and other national databases were queried for Native American patients with MLD. Pedigrees, including birth location, were established by interviewing relatives. We found that cases of MLD and their ancestors are clustered in a portion of the western Navajo Nation to which a small number of Navajo fled after armed conflict with the United States Army in the 1860s. The observed incidence of MLD on the western Navajo Nation is 1/2,520 live births, with an estimated carrier frequency of 1/25 to 1/50. No cases were observed in the eastern part of the Navajo Nation over a period of 18 years (60,000 births). The high incidence of MLD in the western Navajo Nation appears to be the result of a genetic bottleneck and probable founder effect from the mid 19th century: This mechanism may also explain the high incidence of a number of other unique, heritable disorders among the Navajo. The history of the Navajo may also be relevant to other American Indian and Alaskan Native groups that have undergone severe population reduction since the arrival of Europeans in North America.

Assessment of serum-mediated neurotoxicity in Navajo neuropathy.

Navajo neuropathy is a unique sensorimotor neuropathy which is geographically restricted to Navajo children living on the Navajo Reservation. Affected patients present with weakness, loss of sensation in extremities, corneal ulcerations, and a high incidence of childhood infections. Metabolic complications, such as severe liver disease, may further contribute to peripheral nerve injury in affected patients. In this study, serum-mediated injury to rat peripheral nerve was critically assessed. Serum samples from affected Navajo patients were tested in vivo for effects on peripheral nerve function. Injection of serum from affected Navajo patients into rat sciatic nerve produced a modest slowing of nerve conduction velocity without effecting evoked-compound muscle action potential (CMAP) amplitudes. By comparison, injection of serum from patients with MGUS neuropathy, an immune-mediated disorder, diminished evoked-CMAP amplitudes by approximately 70%. Navajo neuropathy sera had no effect in vitro on the neurite outgrowth of developing dorsal root ganglia neurons. The results argue against serum-mediated toxic injury to peripheral nerves in Navajo neuropathy.

Early childhood caries in Indigenous communities: A joint statement with the American Academy of Pediatrics.

The oral health of Indigenous children of Canada (First Nations, Inuit and Métis) and the United States (American Indian and Alaska Native) is a major child health issue. This is exemplified by the high prevalence of early childhood caries (ECC) with resulting adverse health effects, as well as high rates and costs of restorative and surgical treatments under general anesthesia. ECC is an infectious disease that is influenced by multiple factors, including socioeconomic determinants, and requires a combination of approaches for improvement. The present statement includes recommendations for oral health preventive and clinical care for young infants and pregnant women by primary health care providers, community-based health promotion initiatives, oral health workforce and access issues, and advocacy for community water fluoridation and fluoride varnish program access. Further community-based research on the epidemiology, prevention, management and microbiology of ECC in Indigenous communities would be beneficial.

Treatment of snake, insect, scorpion, and spider bites in the pediatric emergency department.

Most people seem to have a visceral fear of snakes, spiders, scorpions, and insects out of proportion to the actual danger they pose. The vast majority of bites and stings cause little more than local pain and never require medical attention. Nevertheless, physicians who work in the emergency department must be prepared to treat the few patients who present with anaphylactic reactions to Hymenoptera stings, as well as to recognize and treat those rare individuals who receive severe envenomation from poisonous snakes, spiders, or scorpions.

Liver disease in Navajo neuropathy.

OBJECTIVE: To describe clinical and histologic features of liver disease in infants and children with Navajo neuropathy (NN). METHODS: Physicians at Navajo Area Indian Health Service facilities and neurologists and gastroenterologists at regional referral hospitals were surveyed for identification of patients born between 1980 and 1994 with known or suspected NN. Clinical records and liver histologic findings were reviewed. RESULTS: Liver disease was present in all children with NN. Three clinical phenotypes of NN were observed, based on age at presentation and course: infantile NN presented in 5 infants before 6 months of age with jaundice and failure to thrive and progressed to liver failure before 2 years of age; childhood NN presented in 6 children between 1 and 5 years of age with liver dysfunction, which progressed to liver failure and death within 6 months; and classical NN presented in 9 children with variable onset of liver disease but progressive neurologic deterioration. Liver histologic findings were characterized by multinucleate giant cells, macrovesicular and microvesicular steatosis, pseudo-acini, inflammation, cholestasis, and bridging fibrosis and cirrhosis. Cases of all 3 phenotypes occurred within the same kindred. CONCLUSIONS: Liver disease is an important component of NN and may be the predominant feature in infants and young children. We propose changing the name of this disease to Navajo neurohepatopathy.

A cluster of microvillous inclusion disease in the Navajo population.

We report 4 unrelated patients with characteristic microscopic findings of microvillous inclusion disease (MID) with early-onset phenotype. All 4 patients came from the Navajo reservation in northern Arizona. A literature search revealed a fifth unrelated Navajo child with MID. The unusually high incidence in this population indicates that a founder effect might be responsible for an increased frequency of this rare genetic disorder in the Navajo. It is recommended that all Navajo infants presenting with severe diarrhea during early infancy undergo investigation for MID.

Navajo neurohepatopathy: a mitochondrial DNA depletion syndrome?

Navajo neurohepatopathy (NNH) is an autosomal recessive disease of full-blooded Navajo children living in the Navajo Reservation of southwestern United States. Clinical features of NNH include peripheral and central nervous system involvement, acral mutilation, corneal scarring or ulceration, liver failure, and metabolic and immunologic derangement. The cause of NNH is unknown, but the clinical features of NNH are similar to those of patients with mitochondrial DNA (mtDNA) depletion. Therefore, we studied mtDNA concentration in the liver from 2 patients with NNH. Using histochemical, biochemical, and molecular techniques, we found evidence of mtDNA depletion, and we propose that the primary defect in NNH is in the nuclear regulation of mtDNA copy number.