RESUMEN
Patients with biallelic mutations for Huntington disease (HD) are rare. We present a 46-year-old female with two expanded Huntingtin (HTT) alleles with just one known affected parent. This is the first reported patient with molecular studies performed to exclude HTT uniparental disomy (UPD). The proband had biparental inheritance of HTT alleles (42/44 CAG repeats). Given the negative UPD results, the proband's unaffected mother either had a reduced penetrance allele that expanded into the full mutation range during transmission to our patient or an unknown full HTT mutation and died before symptom onset, unlikely given no family history of HD and asymptomatic at age 59. We made the novel observation in our literature review that most patients with biallelic HD did not have two full HTT mutations. Most had one HTT allele that was in the intermediate or reduced penetrance ranges or 40 CAG repeats, the lowest limit of the full mutation range. Although the number of patients is small, when an allele in these size ranges was present, generally the age of HD onset was in the 50s. If the second HTT allele had >45 repeats, then onset was typically 20s-30s. While similar ages of onset have been reported for patients with one or two HTT mutations, patients with biallelic mutations may have later onset if an expanded HTT allele has ≤40 CAG repeats. Finally, we propose that "biallelic mutations" or "compound heterozygosity" are more accurate descriptive terms than "homozygosity" when there are two non-identical expanded HTT alleles.
Asunto(s)
Alelos , Enfermedad de Huntington/genética , Proteínas del Tejido Nervioso/genética , Disomía Uniparental/genética , Femenino , Haplotipos , Heterocigoto , Homocigoto , Humanos , Proteína Huntingtina , Enfermedad de Huntington/fisiopatología , Persona de Mediana Edad , Mutación , Linaje , Penetrancia , Repeticiones de Trinucleótidos/genética , Disomía Uniparental/fisiopatologíaRESUMEN
Osteoporosis is a common disorder with significant morbidity and mortality. Clinical risk factors can identify patients most likely to have osteoporosis. Patients who have decreased bone mass are candidates for calcium and vitamin D supplementation; those who have more severe bone loss should be screened for secondary causes and started on medical therapy. First-line therapy most often is a bisphosphonate. Estrogen reduces hip fractures in women. Recombinant parathyroid hormone is reserved for patients who have failed or are not candidates for bisphosphonate therapy. Follow-up dual-emission x-ray absorptiometry is reserved for when a change in bone mineral density will make a difference in therapy.
