ABOPM · Rare Disease

AI note — cites the primary sources.
Bernard G AJHG 2011; Wolf NI et al Neurology 2014; OMIM 607694. Teaching pattern: HPO-driven re-analysis of negative exomes is high-yield — dental findings + leukodystrophy combo is pathognomonic for POLR3-related disorders.

AI note — cites the primary sources.
Kishnani PS Genet Med 2006; ACMG ACT Sheet Pompe disease 2019. Pearl: macroglossia + HCM + hypotonia in infancy is the classic triad; Pompe is now on the RUSP (Recommended Uniform Screening Panel) for newborn screening.

Marcus Freeman · Attending · Genomic pathology · PharmGKB CPIC contributor
Infantile Pompe without ERT has median survival <12mo — the treatment window is small. CRIM (cross-reactive immunologic material) status determines whether immunomodulation protocol is needed to prevent antibody response to alglucosidase alfa. Reference: Kishnani PS et al Genet Med 2006 (Pompe management guideline).

AI note — cites the primary sources.
Ah Mew N GeneReviews 2017; Urea Cycle Disorders Consortium protocols. ABOPM teaching point: exertional rhabdomyolysis + hyperammonemia + normal acylcarnitines = think urea cycle disorder (OTC most common), not primary muscle disease.

Alexa Park · Fellow · Heme/Onc · breast focus
Late-onset OTC in heterozygous females is under-recognized — the manifesting heterozygote state depends on X-inactivation skew. Acute management: stop protein, IV arginine, sodium benzoate/phenylbutyrate, dialysis if NH3 >500. Long-term: low-protein diet + nitrogen scavenger. Reference: Ah Mew N et al GeneReviews 2017 (OTC deficiency).