Comparison of predictive accuracy of knee height equations in children.

Knee height can be a proxy for height when standing height cannot be reliably measured. We compared two commonly used equations (Chumlea and Rumapea) that estimate standing height from knee height. We prospectively enrolled 210 children without scoliosis or kyphosis aged 7-12 years (mean age: 10.2 years, 47.6% males) and measured their knee heights and standing heights. A two-tailed T-test was used to compare predicted heights from each of the equations to actual standing height. Chumlea equation was found to be unreliable (p = 0.0376) while Rumapea equation was found to be reliable in estimating standing height (p = 0.878). Additionally, Rumapea equation was also found to be more accurate than Chumlea equation when results were segregated based on gender and race. In conclusion, the Rumapea equation yields more accurate estimates of standing heights than the Chumlea equation in US children aged 7-12 years.

Computational structural genomics and clinical evidence suggest BCKDK gain-of-function may cause a potentially asymptomatic maple syrup urine disease phenotype.

Maple syrup urine disease (MSUD) is a disorder of branched-chain amino acid metabolism caused by a defect in the branched-chain α-ketoacid dehydrogenase (BCKD) complex (OMIM #248600). The hallmark presentation is encephalopathic crisis in neonates, but can also present with metabolic decompensation, developmental delays, and feeding difficulties. Biochemical evidence for MSUD includes elevated branched-chain amino acids (BCAA) and the pathognomonic presence of alloisoleucine. The BCKD complex contains several subunits associated with autosomal recessive MSUD, while its regulatory proteins have less well-defined disease associations. We report on two families with the same BCKDK variant (c.1115C>G (p.Thr372Arg)). Probands were detected on newborn screening and demonstrated biochemical evidence of MSUD. The variant was identified in reportedly asymptomatic parents and additional family members who had elevated BCAA and alloisoleucine, following an autosomal dominant pattern of inheritance. To better define the functional effect of the variant on the kinase, we completed molecular modeling using sequence-based (2D), structural-based (3D), and dynamic-based (4D) analyses. The BCKDK variant modeling indicated a gain-of-function which leads to impaired BCAA catabolism consistent with the biochemical evidence in this cohort. Combining the evidence gained from molecular modeling with the absence of metabolic decompensation in our patients and several adult family members, despite encountering stressors typically problematic in classic MSUD, we suggest that heterozygous gain-of-function variants in BCKDK may represent a novel biochemical phenotype of MSUD with a benign clinical course.